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Trial record 49 of 214 for:    TETRACYCLINE

Minocycline for the Treatment of Decreased Mental Function in HIV-Infected Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00361257
Recruitment Status : Terminated (This study was terminated early due to futility.)
First Posted : August 8, 2006
Results First Posted : July 26, 2011
Last Update Posted : February 5, 2016
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Neurologic AIDS Research Consortium (NARC)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: Minocycline
Drug: Placebo (Tetracycline)
Enrollment 107
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description 100 mg orally every 12 hours Placebo taken orally every 12 hours
Period Title: Step 1: Minocycline vs. Placebo
Started 52 55
Completed 40 43
Not Completed 12 12
Period Title: Step 2: Minocycline(Open Label) for All
Started 28 [1] 34 [2]
Completed 13 19
Not Completed 15 15
[1]
40 participants completed Step 1; however,12 decided not to enroll Step 2,so 40-12=28 started Step 2
[2]
43 participants completed Step 1; however, 9 decided not to enroll Step 2,so 43-9=34 started Step 2.
Arm/Group Title Minocycline Matching Placebo Total
Hide Arm/Group Description 100 mg orally every 12 hours Placebo taken orally every 12 hours Total of all reporting groups
Overall Number of Baseline Participants 52 55 107
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 55 participants 107 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
52
 100.0%
54
  98.2%
106
  99.1%
>=65 years
0
   0.0%
1
   1.8%
1
   0.9%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 52 participants 55 participants 107 participants
50  (7) 52  (7) 51  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 55 participants 107 participants
Female
5
   9.6%
13
  23.6%
18
  16.8%
Male
47
  90.4%
42
  76.4%
89
  83.2%
Cognitive Performance Score NPZ-8   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-0.75  (0.90) -1.03  (0.98) -0.90  (0.95)
[1]
Measure Description:

Cognitive performance is measured by NPZ-8. The NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery:

  1. Grooved Pegboard Dominant Hand (GPD)
  2. Grooved Pegboard Non-dominant hand (GPN)
  3. Choice Reaction Time (CRT)
  4. Sequential Reaction Time (QRT)
  5. Timed Gait (TIG)
  6. Trail Making Part A (TMA)
  7. Trail Making Part B (TMB)
  8. Symbol Digit (SYD)
Global Deficit Z-Score (GDS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-0.86  (0.72) -1.08  (0.90) -0.97  (0.82)
[1]
Measure Description: GDS is defined as the average of age and education adjusted z-scores of 14 individual deficit scores in the test battery, including Time Gait, Grooved Pegboard Test for the dominant and non-dominant hands, Trail Making Test parts A and B, Symbol Digit Test, simple and sequential reaction time - CalCAP, Hopkins Verbal Learning Test (Revised)- Learning, Delayed Recall and Recognition trials, and Stroop Color Interference Test-color, word, and interference tasks.
Cognitive Gross Motor Function Domain Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-2.44  (3.10) -3.66  (4.16) -3.06  (3.71)
[1]
Measure Description: The cognitive gross motor function is age and education adjusted z-score of Timed Gait.
Fine Motor Function Domain Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-0.35  (0.96) -0.73  (0.99) -0.55  (0.99)
[1]
Measure Description: This is an average z-scores of Grooved Pegboard Dominant and Non-Dominant Hand Tests adjusted for age, sex, education, and African-American ethnicity. The grooved pegboard is a manipulative dexterity test requiring rapid visual-motor coordination. The test is completed using the dominant hand (GPD) and then using the non-dominant hand (GPN). The score for each hand is the time in seconds that the participant takes to complete the entire board.
Psychomotor Function Domain Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
0.15  (1.00) 0.04  (1.03) 0.10  (1.01)
[1]
Measure Description: This is an average of z-scores of Trail Making Part A (TMA) and Trail Making Part B (TMB) tests adjusted for age, sex, education, and African-American ethnicity. The TMA and TMB tests are measures of planning ability, visual-motor speed and concentration. Subjects are required to connect randomly placed numbers in sequence (1-25 for TMA) or to sequentially connect both numbers and letters while alternating back and forth (1-A-2-B-3-C-4-D etc. for TMB). Scores are the time in seconds required to complete the tasks.
Fine Motor/Nonverbal Function Domain Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-1.11  (1.15) -1.24  (1.18) -1.18  (1.16)
[1]
Measure Description: This score is a age and education adjusted z score of Symbol Digit Test (SYD). This test assesses the participant's ability to maintain rapid visual-motor sequencing in a timed test. The score is the total number of correctly transcribed numbers in the time limit (90 seconds). Participants receive 1 point for each item filled in correctly.
Information Processing Function Domain Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-1.05  (1.52) -1.03  (1.49) -1.04  (1.50)
[1]
Measure Description: This is the average age and education adjusted z-scores of simple and sequential reaction time tests adjusted for age and education.
Verbal Memory Domain Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-1.33  (1.16) -1.41  (1.12) -1.37  (1.14)
[1]
Measure Description: This is the average of z-scores of Hopkins Verbal Learning Test- Revised, Learning and Delayed Recall Tests adjusted for age and education. The recognition test list comprises 24 words, consisting of 12 words from the original list and 12 "distracters". The subject must answer "yes" if the word was from the list and "no" otherwise. Twenty minutes after the third list from verbal learning and immediate recall, delayed recall is assessed by asking the subject to recall as many words as possible from the list. The score is the number of words that are correctly recalled from the original list.
Frontal Systems Function Domain Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-0.79  (0.98) -1.05  (1.57) -0.92  (1.32)
[1]
Measure Description: This is the average age and education adjusted z-scores of Stroop Color Interference Test (CTP) and interference task (STP). The Stroop Task is a measure of divided attentional abilities. Performance is measured by the amount of time required to read each of three cards: (1) blocks of colors, (2) names of colors, and (3) colored words. For each task, the time (in seconds) is the score that should be recorded on the form. A task that cannot be completed in 240 seconds is scored as incomplete.
Karnofsky Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 52 participants 55 participants 107 participants
70 5 0 5
80 13 16 29
90 21 34 55
100 8 5 13
missing 5 0 5
[1]
Measure Description:

Karnofsky performance score is ranged from 100 to 0:

100: Normal; 90: Able to Carry on normal Activity; 80: Normal Activity with Effort; Some Signs or Symptoms of Disease; 70: Cares for Self, Unable to Carry on Normal Activity or to Do Active Work; 60: Requires Occasional Assistance but is Able to Care for Most of Needs; 50: Requires Considerable Assistance and Frequent Medical Care; 40: Disabled, Requires Special Care and Assistance; 30: Severely Disabled; Hospitalization Indicated Although Death is Not Imminent; 20: Very Sick; 10: Morbibund, Fatal Processes Progressing Rapidly; 0: Death

Cluster of Differentiation 4 (CD4)   [1] 
Mean (Standard Deviation)
Unit of measure:  Copies/mm^3
Number Analyzed 52 participants 55 participants 107 participants
551.65  (312.96) 535.49  (253.11) 543.35  (282.53)
[1]
Measure Description: CD4 counts by group at baseline
Cluster of Differentiation 8 (CD8)   [1] 
Mean (Standard Deviation)
Unit of measure:  Copies/mm^3
Number Analyzed 52 participants 55 participants 107 participants
925.58  (370.48) 838.78  (353.73) 880.96  (362.88)
[1]
Measure Description: CD8 counts by group at baseline
HIV-1 Plasma RiboNucleic Acid (RNA) Viral Loads   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 52 participants 55 participants 107 participants
Plasma RNA VL >=30 copies/mL 7 6 13
Plasma RNA VL < 30 copies/mL 42 41 83
missing 3 8 11
[1]
Measure Description: HIV Plasma RNA viral load less than 30 copies/mL is undetectable, the values will be imputed as 30 copies/mL.
HIV-1 CerebroSpinal Fluid (CSF) RNA Viral Loads (VL)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 52 participants 55 participants 107 participants
CSF RNA VL >=30 copies/mL 1 2 3
CSF RNA VL <30 copies/mL 20 18 38
missing 31 35 66
[1]
Measure Description: HIV CSF RNA viral load less than 30 copies/mL is undetectable, the values will be imputed as 30 copies/mL.
Central Nervous System (CNS) Penetration Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 52 participants 55 participants 107 participants
7  (3) 7  (3) 7  (3)
[1]
Measure Description: The baseline CNS penetration score is calculated based on the revised CNS penetration-effectiveness ranks (provided by Dr. Scott Letendre). The score is simply a sum of the ranks of all drugs which participants took at baseline. The better the drug penetrates, the higher the score. The range of ranks are 1 to 4, so the CNS penetration score is integer numbers greater than 1.
Stratification Variable 1 - CSF Viral Load (VL) - Pre-baseline   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 52 participants 55 participants 107 participants
CSF RNA VL < 30 copies/mL 21 22 43
CSF RNA VL >= 30 copies/mL 3 4 7
No Lumbar Punctures (LPs) 28 29 57
[1]
Measure Description: Participants were stratified based on two factors. One is CSF HIV-1 RNA. This variable has three levels using the TaqMan assay in CSF: (1) HIV CSF RNA VLs ≥30 copies/mL (detectable), <30 copies/mL (Undetectable), or no lumbar punctures (LPs). The assessment was conducted BEFORE the baseline in order to use this information for randomization.
Stratification Variable 2 - Objective or subjective Neuropsychological test - Pre-baseline   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 52 participants 55 participants 107 participants
Objective Neuropsychological (NP) Test 5 7 12
Subjective NP Test 47 48 95
[1]
Measure Description: The 2nd stratification factor is progressive neurocognitive decline defined by objective or subjective criteria at pre-baseline. A decline of at least 1.0 standard deviation below age-matched and education-matched controls on two or more independent tests or 2.0 standard deviations below age-matched and education-matched controls on one test within 1 year before entry is defined as objective decline. Otherwise, subjective neurocognitive decline is defined by the participant or family member or caregiver AND a Center for Epidemiological Studies Depression score <16 within 45 days before entry.
Instrumental Activities of Daily Living (IADL) Summary Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 52 participants 55 participants 107 participants
0.12  (0.15) 0.13  (0.16) 0.12  (0.15)
[1]
Measure Description: The IADL questionnaire has 16 common tasks: 1. Housekeeping; 2.Managing Finances; 3. Buying Groceries; 4.Cooking; 5. Planning Social Activities; 6.Understanding Reading Materials/TV; 7.Transportation; 8.Using the Telephone; 9.Home Repairs; 10.Bathing; 11.Dressing; 12.Shopping; 13.Laundry; 14.Taking/Keeping Track of Medication; 15.Child Care; 16.Work. For each task, if the score at the time of evaluation is worse than the best in the past, an indicator of 1 is given; otherwise 0. The IADL score is a sum of 16 indicators divided by 16. The lower score indicates better. The range is from 0 to 1.
Medication Management Test (MMT) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 52 participants 55 participants 107 participants
14.72  (1.41) 14.09  (2.52) 14.39  (2.08)
[1]
Measure Description: The medication management test (modified) is designed to assess participants' medication management ability and their own medications and management. It’s the number of how many times participants correctly answered 16 questions.
Alternate Psychomotor Function Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-0.54  (0.82) -0.63  (0.92) -0.58  (0.87)
[1]
Measure Description: This is the average of z scores of Trail Making Part A and Symbol Digit Tests. Trail Making Part A z score was adjusted for age, sex, education, and African-Ametrican ethnicity. Symbol Digit z score was adjusted for age and education.
Alternate Verbal Memory Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-1.33  (1.16) -1.41  (1.12) -1.37  (1.14)
[1]
Measure Description: This is the average of age and education adjusted z scores of standardized trials 1 to 3 and delayed recall tests.
Alternate Frontal Systems Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 52 participants 55 participants 107 participants
-0.04  (0.86) -0.13  (1.09) -0.09  (0.98)
[1]
Measure Description: This is average of z scores of standardized interference task and trailmaking part b tests. The interference task z score was adjusted for age and education. The trailmaking part b z score was adjusted for age, sex, education, and African-American ethnicity.
1.Primary Outcome
Title Change in Cognitive Performance Compared to Baseline
Hide Description

Th cognitive performance is measured by NPZ-8. NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery. These eight tests are:

  1. Grooved Pegboard Dominant Hand (GPD)
  2. Grooved Pegboard Non-dominant hand (GPN)
  3. Choice Reaction Time (CRT)
  4. Sequential Reaction Time (QRT)
  5. Timed Gait (TIG)
  6. Trail Making Part A (TMA)
  7. Trail Making Part B (TMB)
  8. Symbol Digit (SYD) The primary outcome is NPZ-8 score at week24 - NPZ-8 score at baseline.
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The descriptive statistics above were based on the observed data; however, the statistical analysis was conducted by the ITT analysis and the missing outcomes at week 24 were imputed based on multiple regression imputations.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 48
Mean (Standard Deviation)
Unit of Measure: z-score
0.12  (0.71) 0.17  (0.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24-week change of NPZ-8 in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.651
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for stratification variables, the CNS penetration score, and the baseline NPZ-8 score.
Method of Estimation Estimation Parameter Slope
Estimated Value 0.064
Confidence Interval (2-Sided) 95%
-0.258 to 0.386
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.164
Estimation Comments The total number used for the statistical analysis was 107 (52 in the minocycline arm and 55 in the placebo arm).
2.Secondary Outcome
Title Change in Global Deficit Z-Score (GDS)
Hide Description GDS on the test battery is the simple average of all 14 individual deficit scores in the test battery, including Time Gait, Grooved Pegboard Test for the dominant and non-dominant hands, Trail Making Test parts A and B, Symbol Digit Test, simple and sequential reaction time - CalCAP, Hopkins Verbal Learning Test (Revised)- Learning, Delayed Recall and Recognition trials, and Stroop Color Interference Test-color, word, and interference tasks. The outcome is the 24 week change of GDS Z-score (24 week-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on the observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 48
Mean (Standard Deviation)
Unit of Measure: z-score
0.11  (0.58) 0.09  (0.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24-week changes in Global Deficit Score (GDS) between the minocycline and placebo groups are the same.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.434
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for stratification variables, the CNS penetration score, and the baseline GDS score.
Method of Estimation Estimation Parameter Slope
Estimated Value 0.091
Confidence Interval (2-Sided) 95%
-0.140 to 0.323
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.116
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Investigator's Clinical Global Impression Score (ICGIS)
Hide Description

Clinicians were asked to rate their overall impression about the clinical improvement or worsening of his/her study participants. They can choose from the following 7 levels: (0) No Change, (1) Mild Improvement, (2) Moderate Improvement, (3) Marked Improvement, (4) Mild Worsening, (5) Moderate Worsening, and (6) Marked Worsening.

For the analysis, we simplified the outcome into the following 3 levels: (0) worsened, (1) No Change, and (2) Improved.

Time Frame At week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 45
Measure Type: Number
Unit of Measure: participants
Worsened 4 2
No Change 28 31
Improved 9 12
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis is that the 24 week changes of participants' clinical status in the minocycline group were the same as the ones in the placebo group based on ICGIS.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.337
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Cumulative Logistic
Comments The model was adjusted for the stratification variables and the CNS penetration score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.569
Confidence Interval (2-Sided) 95%
0.625 to 3.936
Parameter Dispersion
Type: Standard Deviation
Value: 0.469
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in Cognitive Gross Motor Function Domain Z-Score
Hide Description The cognitive gross motor function is a age and education adjusted z score of Timed Gait (TIG). The outcome is the 24 week change of cognitive gross motor function domain z-scores (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on the observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 42
Mean (Standard Deviation)
Unit of Measure: z-score
0.22  (1.61) 0.08  (2.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis is that the 24 week change in the cognitive gross motor function domain score in the minocycline group is the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.243
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the stratification variables, the CNS penetration score, and the baseline cognitive gross motor function domain score.
Method of Estimation Estimation Parameter Slope
Estimated Value 0.502
Confidence Interval (2-Sided) 95%
-0.349 to 1.354
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.428
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in Fine Motor Function Domain Z-Score
Hide Description The fine motor function domain score is an average of age, sex, education, and African-American ethnicity adjusted z scores of Grooved Pegboard Dominant Hand (GPD) and Grooved Pegboard Non-dominant hand (GPN). The outcome is a 24 week change of the fine motor function domain z-score (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 48
Mean (Standard Deviation)
Unit of Measure: z-score
0.27  (0.84) 0.05  (0.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 week change in fine motor function domain score in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the stratification variables, the CNS penetration score, and the baseline fine motor function domain score.
Method of Estimation Estimation Parameter Slope
Estimated Value 0.293
Confidence Interval (2-Sided) 95%
-0.011 to 0.596
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.153
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in Psychomotor Function Domain Z-Score
Hide Description The psychomotor function domain score us the average of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA) and Trail Making Part B (TMB). The outcome is the 24 week change of psychomotor function domain z-scores (week24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 48
Mean (Standard Deviation)
Unit of Measure: z-score
0.07  (0.66) 0.15  (0.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 change of psychomotor function domain score in the minocycline group is the same as in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.572
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for stratified variables, the baseline CNS penetration score, and the baseline psychomotor function domain score.
Method of Estimation Estimation Parameter Slope
Estimated Value -0.083
Confidence Interval (2-Sided) 95%
-0.375 to 0.209
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.147
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change in Fine Motor/Nonverbal Function Domain Z-Score
Hide Description The fine motor/nonverbal function domain score is a age and education adjusted z score of Symbol Digit Test (SYD) The outcome is the 24 change of fine motor/nonverbal function domain z-score (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 48
Mean (Standard Deviation)
Unit of Measure: z-score
-0.15  (0.76) -0.07  (0.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 week change of fine motor/nonverbal function domain score in the minocycline group was the same as in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.637
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the stratification variables, the CNS penetration score, and the baseline fine motor/nonverbal function domain score.
Method of Estimation Estimation Parameter Slope
Estimated Value -0.086
Confidence Interval (2-Sided) 95%
-0.449 to 0.276
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.182
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change in Information Processing Function Domain Z-Score
Hide Description The information processing function domain score is the average of age and education adjusted z scores of simple and sequential reaction time - CalCAP. The outcome is the 24 week change of information processing function domain z-scores (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 40 45
Mean (Standard Deviation)
Unit of Measure: z-score
0.14  (1.65) 0.20  (1.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 week change of information processing function domain score in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.754
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the stratification variables, the CNS penetration score, and the baseline information processing function domain score.
Method of Estimation Estimation Parameter Slope
Estimated Value -0.074
Confidence Interval (2-Sided) 95%
-0.544 to 0.396
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.236
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change in Verbal Memory Domain Z-Score
Hide Description The verbal memory domain score is the average of age and education adjusted z scores of Hopkins Verbal Learning Test- Revised, Learning and Delayed Recall. The outcome is the 24 week change of verbal memory domain z-scores (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 47
Mean (Standard Deviation)
Unit of Measure: z-score
0.18  (0.96) 0.02  (1.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 week change of verbal memory domain score in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.484
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the stratification variables, the baseline CNS penetration score, and the baseline verbal memory domain score.
Method of Estimation Estimation Parameter Slope
Estimated Value 0.145
Confidence Interval (2-Sided) 95%
-0.266 to 0.558
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.207
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change in Frontal Systems Function Domain Z-Score
Hide Description The frontal systems function domain score is the average of age and education adjusted z scores of Stroop Color Interference Test (CTP) and interference task (STP). The outcome is the 24 week change of frontal systems function domain z-score (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 47
Mean (Standard Deviation)
Unit of Measure: z-score
-0.04  (0.78) 0.21  (1.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 week change of frontal systems function domain score in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.467
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the stratification variables, the baseline CNS penetration score, and the baseline frontal systems function domain score.
Method of Estimation Estimation Parameter Slope
Estimated Value -0.126
Confidence Interval (2-Sided) 95%
-0.467 to 0.216
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.172
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change in Karnofsky Performance Score
Hide Description

The original Karnofsky performance score is 11 level score which ranges between 0 to 100. The score 100 means normal and 0 means death; therefore, higher score means higher ability to perform daily tasks.

For the analysis, a new dichotomous variable (no change/worse vs. better at 24 weeks compared to baseline) was created.

Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 39 45
Measure Type: Number
Unit of Measure: participants
No Change/Worse 33 42
Better 6 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the proportion of being "better" at 24 weeks in minocycline group was the same as in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.234
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the CNS penetration score. The stratification variables could not be included in the model since the model fit was poor.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.476
Confidence Interval (2-Sided) 95%
0.575 to 10.668
Parameter Dispersion
Type: Standard Deviation
Value: 1.048
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks)
Hide Description The outcome was the 24 week change in CD4 cell count (week 24-baseline).
Time Frame At baseline and weeks 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 40 34
Mean (Standard Deviation)
Unit of Measure: cells/mm^3
24.10  (141.22) 8.24  (143.02)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 week change in CD4 cell counts in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.574
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for stratification variables, the baseline CNS score, and the baseline CD4 cell count.
Method of Estimation Estimation Parameter Slope
Estimated Value 19.09
Confidence Interval (2-Sided) 95%
-48.26 to 86.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 33.75
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks)
Hide Description The outcome was the 24 week change of CD8 cell counts (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 40 34
Mean (Standard Deviation)
Unit of Measure: cells/mm^3
43.90  (244.51) 0.00  (253.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 week change in CD8 cell count in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.502
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the stratification variables, the baseline CNS penetration score, and the baseline CD8 cell counts.
Method of Estimation Estimation Parameter Slope
Estimated Value 40.43
Confidence Interval (2-Sided) 95%
-79.12 to 159.97
Parameter Dispersion
Type: Standard Error of the mean
Value: 59.91
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms
Hide Description Grade or higher means that adverse events were moderate, severe, or life-threatening, or death. Grade 2 or higher adverse events are lised in the Adverse Event section.
Time Frame Throughout study up to week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis includes all randomized participants. A total of 37 minocycline and 38 placebo participants reported Grade 2 or higher toxicity and/or signs and symptoms during 48 weeks.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 52 55
Measure Type: Number
Unit of Measure: participants with an event
0 - 4 weeks 29 32
4.01 - 12 weeks 5 3
12.01 - 24 weeks 2 1
24.01 - 48 weeks 1 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the time to Grade 2 or higher toxicity and/or signs and symptoms in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.967
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
15.Secondary Outcome
Title Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load
Hide Description The original scale of HIV RNA viral load is between 30 copies/mL to infinitive. The minimum score of 30 is the lowest detectable value. The summary table categorized this continuous value to a dichotomous variable (<30 copies/mL and >= 30 copies/mL).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The summary statistics were based on observed data. No statistical analysis was conducted.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 20 21
Measure Type: Number
Unit of Measure: participants
>= 30 copies/mL at base, >= 30 at week 24 1 0
>= 30 copies/mL at base, < 30 at week 24 0 2
< 30 copies/mL at base, >= 30 at week 24 2 0
< 30 copies/mL at base, < 30 at week 24 17 19
16.Secondary Outcome
Title Changes in Instrumental Activities of Daily Living Questionnaire
Hide Description The Instrumental Activities of Daily Living (IADL) questionnaire is designed to learn more about how subjects are able to perform common tasks. There are 16 common tasks. For each task, if the score at the time of evaluation is worse than the best in the past, an indicator of 1 is given. Otherwise, the indicator is 0. The overall IADL score is a sum of 16 indicators divided by 16; therefore, the range is between 0 and 1 and the lower score is better. The 24-week change of IADL score was changed into a categorical variable (no change/worse vs. better) at week 24 compare to baseline.
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 42 43
Measure Type: Number
Unit of Measure: participants
No Change/Worse 30 32
Better 12 11
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the proportion of participants who got better at week 24 compared to baseline in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.890
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Logistic
Comments The model was adjusted for the stratification variables and the baseline CNS penetration score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.071
Confidence Interval (2-Sided) 95%
0.405 to 2.837
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.497
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Changes in Medication Management Test (Modified)
Hide Description The medication management test (modified) is designed to assess participants' medication management ability and their own medications and management. It’s the number of how many times participants correctly answered 16 questions. The score ranges between 0 and 16, and higher score indicates better medication management.
Time Frame At baseline and weeks 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 43 46
Mean (Standard Deviation)
Unit of Measure: scores on a scale
0.16  (1.57) 0.48  (2.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 change of medication management test score in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.304
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the stratification variables, the baseline CNS penetration score, and the baseline medication management score.
Method of Estimation Estimation Parameter Slope
Estimated Value -0.405
Confidence Interval (2-Sided) 95%
-1.182 to 0.373
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.391
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only)
Hide Description Protein marker of oxidative stress (Ceramides, Monohexosylceramides, Dihydro Glycosyl Galceramides, and Dihexosylceramides). For all markers, the outcome is the 24 week change (week 24-baseline).
Time Frame At pre-entry and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were willing to receive the lumber punctures at week 0 and 24.
Arm/Group Title Arm 1: Minocycline Arm 2: Matching Placebo
Hide Arm/Group Description:

100 mg orally every 12 hours

Minocycline: Tetracycline antibiotic, 100 mg taken orally every 12 hours

orally every 12 hours

Placebo (Tetracycline): Tetracycline antibiotic placebo, orally every 12 hours

Overall Number of Participants Analyzed 6 8
Median (Inter-Quartile Range)
Unit of Measure: counts per second
Ceramides (counts per second)
0.0007
(-0.0001 to 0.0060)
-0.0051
(-0.0177 to 0.0006)
Monohexosylceramides (counts per second)
0.0013
(-0.0007 to 0.0330)
-0.0066
(-0.0279 to -0.0004)
Dihydro Glycosyl Galceramides (counts per second)
0.0201
(0.0043 to 0.0355)
-0.0048
(-0.0180 to -0.0010)
Dihexosylceramides (counts per second)
0.0005
(-0.0003 to 0.0070)
-0.0043
(-0.0090 to -0.0001)
19.Secondary Outcome
Title Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
Hide Description Protein markers of oxidative stress (Protein carbonyls) and markers of immune activation (TNF-a, IL-6,CXCL8, Hepatocyte growth factor, Osteopontin, sFAS, sFAS ligand, and CXCL12). For all markers, the outcome is the 24 week change (week 24-baseline).
Time Frame At pre-entry and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were willing to receive the lumber punctures at week 0 and 24.
Arm/Group Title Arm 1: Minocycline Arm 2: Matching Placebo
Hide Arm/Group Description:

100 mg orally every 12 hours

Minocycline: Tetracycline antibiotic, 100 mg taken orally every 12 hours

orally every 12 hours

Placebo (Tetracycline): Tetracycline antibiotic placebo, orally every 12 hours

Overall Number of Participants Analyzed 8 13
Median (Inter-Quartile Range)
Unit of Measure: pg/mL
Protein carbonyls (pg/ml)
4.0
(3.32 to 82.29)
13.2
(0.13 to 39.74)
TNF-α (pg/mL)
0.04
(0.00 to 0.31)
0.14
(0.00 to 0.65)
IL-6 (pg/mL)
-0.29
(-0.67 to 2.58)
0.95
(-0.79 to 2.41)
CXCL8 (pg/mL)
0.34
(-3.07 to 5.97)
-6.13
(-12.5 to 3.07)
Hepatocyte growth factor (pg/mL)
16.09
(-21.54 to 168.99)
90.48
(6.70 to 250.39)
Osteopontin (pg/mL)
-5208.94
(-11579.90 to 7088.79)
673.55
(-14689.54 to 23344.10)
sFAS (pg/mL)
0.68
(-9.35 to 77.79)
134.1
(26.41 to 279.87)
sFAS ligand (pg/mL)
-0.27
(-0.65 to 0.06)
0.11
(-0.07 to 1.47)
CXCL12 (pg/mL)
204.39
(-164.20 to 1152.41)
1,071.84
(-96.75 to 1678.84)
20.Secondary Outcome
Title Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only)
Hide Description Protein marker of oxidative stress (Neurofilament heavy polypeptide). The outcome is the 24 week change (week 24-baseline).
Time Frame At pre-entry and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were willing to receive the lumber punctures at week 0 and 24.
Arm/Group Title Arm 1: Minocycline Arm 2: Matching Placebo
Hide Arm/Group Description:

100 mg orally every 12 hours

Minocycline: Tetracycline antibiotic, 100 mg taken orally every 12 hours

orally every 12 hours

Placebo (Tetracycline): Tetracycline antibiotic placebo, orally every 12 hours

Overall Number of Participants Analyzed 5 5
Median (Inter-Quartile Range)
Unit of Measure: Pixels/mm^2
-59.3
(-76.05 to -36.69)
-3.04
(-6.31 to 59.86)
21.Secondary Outcome
Title Changes in Neurotransmitter Levels (Unit = uM Only)
Hide Description Neurotransmitter levels (Glutamate, Tryptophan, Anthranilic Acid, Quinolinic Acid, Kynurenin, and 3-Hydroxykynurenine). The outcome is the 24 week change (week 24-baseline).
Time Frame At pre-entry and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were willing to receive the lumber punctures at week 0 and 24.
Arm/Group Title Arm 1: Minocycline Arm 2: Matching Placebo
Hide Arm/Group Description:

100 mg orally every 12 hours

Minocycline: Tetracycline antibiotic, 100 mg taken orally every 12 hours

orally every 12 hours

Placebo (Tetracycline): Tetracycline antibiotic placebo, orally every 12 hours

Overall Number of Participants Analyzed 4 6
Median (Inter-Quartile Range)
Unit of Measure: uM
Glutamate (uM)
5.09
(-11.01 to 13.41)
-1.08
(-1.20 to 10.88)
Tryptophan (uM)
-0.21
(-0.78 to 0.12)
0.07
(0.05 to 0.21)
Anthranilic Acid (uM)
0.0
(-2.25 to 10.87)
0.0
(-7.14 to 6.15)
Quinolinic Acid (uM)
-0.55
(-7.94 to 0.00)
0.0
(-9.07 to 4.11)
Kynurenin (uM)
6.85
(0.01 to 46.75)
6.97
(0.00 to 23.90)
3-Hydroxykynurenine (uM)
-4.09
(-11.51 to 0.02)
-0.83
(-5.97 to 0.00)
22.Secondary Outcome
Title Changes in Alternate Psychomotor Function Z-Score
Hide Description The alternate psychomotor function is defined as the mean of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA), and age and education adjusted z score of Symbol Digit (SYD). The outcome is the 24 week change in alternate psychomotor function z-score (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on the observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 48
Mean (Standard Deviation)
Unit of Measure: z-score
-0.03  (0.66) 0.05  (0.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 week change in alternate psychomotor function score in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.506
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the stratification variables, the baseline CNS penetration score, and the baseline alternate psychomotor function score.
Method of Estimation Estimation Parameter Slope
Estimated Value -0.097
Confidence Interval (2-Sided) 95%
-0.388 to 0.193
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.146
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Changes in Alternate Verbal Memory Z-Score
Hide Description The alternate verbal memory was defined as a mean of age and education adjusted z score of trials 1 to 3 and delayed recall tests. The outcome is the 24 week change in alternate verbal memory z-score (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis is based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 47
Mean (Standard Deviation)
Unit of Measure: z-score
0.18  (0.96) 0.02  (1.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was that the 24 week change in the alternate verbal memory score in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.484
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for stratification variables, baseline CNS penetration score, and the baseline alternate verbal memory score.
Method of Estimation Estimation Parameter Slope
Estimated Value 0.146
Confidence Interval (2-Sided) 95%
-0.266 to 0.558
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.207
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Changes in Alternate Frontal Systems Z-Score
Hide Description The alternate frontal systems was defined as a mean of age and education adjusted z score of Interference task, and age, sex, education, and African-American ethnicity adjusted z score of Trail Making Part B. The outcome was the 24 week change in alternate frontal systems z-score (week 24-baseline).
Time Frame At baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on observed data.
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description:
100 mg orally every 12 hours
Placebo taken orally every 12 hours
Overall Number of Participants Analyzed 41 47
Mean (Standard Deviation)
Unit of Measure: z-score
0.03  (0.67) -0.07  (0.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Matching Placebo
Comments The null hypothesis was the 24 week change of alternate frontal systems score in the minocycline group was the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.690
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for stratification variables, baseline CNS penetration score, and the baseline alternate frontal systems score.
Method of Estimation Estimation Parameter Slope
Estimated Value 0.055
Confidence Interval (2-Sided) 95%
-0.217 to 0.327
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.137
Estimation Comments [Not Specified]
Time Frame Up to 48 weeks since the randomization.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Minocycline Matching Placebo
Hide Arm/Group Description 100 mg orally every 12 hours Placebo taken orally every 12 hours
All-Cause Mortality
Minocycline Matching Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Minocycline Matching Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/52 (13.46%)      3/55 (5.45%)    
Blood and lymphatic system disorders     
Blood amylase increased  1 [1]  1/52 (1.92%)  1 0/55 (0.00%)  0
Blood triglycerides increased  1  1/52 (1.92%)  1 0/55 (0.00%)  0
General disorders     
Tooth infection  1 [2]  1/52 (1.92%)  1 0/55 (0.00%)  0
Hypertension  1  0/52 (0.00%)  0 1/55 (1.82%)  1
Hepatobiliary disorders     
Alanine aminotransferase increased  1  1/52 (1.92%)  1 0/55 (0.00%)  0
Nervous system disorders     
Vocal cord paralysis  1 [3]  1/52 (1.92%)  1 0/55 (0.00%)  0
Psychiatric disorders     
Suicidal ideation  1 [4]  1/52 (1.92%)  1 0/55 (0.00%)  0
Suicidal attempt  1 [5]  0/52 (0.00%)  0 1/55 (1.82%)  1
Renal and urinary disorders     
Renal failure  1 [6]  0/52 (0.00%)  0 1/55 (1.82%)  1
Skin and subcutaneous tissue disorders     
Basal cell carcinoma  1 [7]  1/52 (1.92%)  1 0/55 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
[1]
Grade 4: Life-threatening
[2]
Tooth discoloration
[3]
Amyotrophic lateral sclerosis (ALS)
[4]
Resulted in hospitalization
[5]
By medication overdose
[6]
Requires dialysis
[7]
On nose
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Minocycline Matching Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/52 (34.62%)      34/55 (61.82%)    
Gastrointestinal disorders     
Diarrhea/Loose  1  5/52 (9.62%)  5 3/55 (5.45%)  3
Nausea  1  2/52 (3.85%)  2 4/55 (7.27%)  4
General disorders     
Fatigue  1  4/52 (7.69%)  4 3/55 (5.45%)  3
Pain  1  5/52 (9.62%)  9 9/55 (16.36%)  9
Sob  1  0/52 (0.00%)  0 4/55 (7.27%)  4
Headache  1  1/52 (1.92%)  1 7/55 (12.73%)  7
Respiratory, thoracic and mediastinal disorders     
Cough  1  2/52 (3.85%)  2 4/55 (7.27%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Originally, 100 participants were expected to enroll. As of the early termination notice, 107 participants were randomized, yet not all subjects could complete the 24 week assessment.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In accordance with the Clinical Trial Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
EMail: ACTGCT.Gov@s-3.com
Layout table for additonal information
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00361257     History of Changes
Other Study ID Numbers: ACTG A5235
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: August 4, 2006
First Posted: August 8, 2006
Results First Submitted: January 28, 2011
Results First Posted: July 26, 2011
Last Update Posted: February 5, 2016