Minocycline for HIV+ Cognitive Impairment in Uganda - Full Text View

Sponsor:	Johns Hopkins University
Collaborator:	Makerere University
Information provided by:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00855062

Purpose

Purpose: The purpose of the study is to assess the safety and effectiveness of minocycline, an antibiotic, in the treatment of Human immunodeficiency virus (HIV)-associated cognitive impairment in Uganda.

Study Design: Treatment, 24-week Randomized, Placebo-Controlled, Double-Blind Phase with Optional 24-week Open Label Phase for Subjects with a cluster of differentiation 4 (CD4) Count in the 251-350 Range

Arm 1: Minocycline 100 mg orally every 12 hours (50 subjects)
Arm 2: Matching placebo orally every 12 hours (50 subjects)

Primary Objective:

· To examine whether minocycline treatment will improve cognitive performance after 24 weeks compared to baseline

Secondary Objectives:

To examine whether minocycline treatment for 24 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment
To examine whether minocycline treatment for 48 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment
To examine whether minocycline treatment for 24 weeks improves functional impairment

Condition	Intervention	Phase
HIV-associated Cognitive Impairment HIV Infections	Drug: minocycline Drug: minocycline placebo capsule	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Minocycline in the Treatment of HIV-Associated Cognitive Impairment in Uganda

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Dementia HIV/AIDS

Drug Information available for: Minocycline Minocycline hydrochloride

U.S. FDA Resources

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:

24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
The U NP Sum is defined as the average of z scores for 9 neuropsychological test subcomponents in the neuropsychological test battery (i.e. the average of norm-adjusted ("z") scores for Grooved Pegboard Dominant Hand, Grooved Pegboard Non-dominant Hand, Color Trails 1, Color Trails 2, Symbol Digit, WHO-UCLA Verbal Learning test Trial 5, WHO-UCLA Verbal Learning test delayed recall, Digit Span forward and Digit Span backward). The outcome is defined as U NP Sum at week 24 - U NP Sum at baseline.

Secondary Outcome Measures:

24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
24-week Change of Karnofsky Performance Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. [ Time Frame: Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24 ] [ Designated as safety issue: Yes ]
The outcome is the time to first Grade ≥ 2 toxicity and/or sign and symptoms from study treatment initiation up to week 24. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event.
Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms [ Time Frame: Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks ] [ Designated as safety issue: Yes ]
The outcome is the time of first Grade ≥ 2 toxicity and/or sign and symptoms from treatment initiation up to 48 weeks. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event.
24-week Change of CD4 Cell Counts [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
The outcome is defined as CD4 cell count at week 24 - CD4 cell count at baseline. The unit is cells/mm^3.
48-week Change of CD4 Cell Counts [ Time Frame: At baseline and week 48 ] [ Designated as safety issue: No ]
The outcome is defined as CD4 cell count at week 48 - CD4 cell count at baseline. The unit is cells/mm^3.
24-week Change of Instrumental Activities of Daily Living [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
The outcome is the HIV RNA plasma viral loads (Log10 transformed) at week 24 - the viral loads (Log10 transformed) at baseline.
24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
The outcome is the total CES-D score at week 24 - the total CES-D score at baseline.

The total CES-D score is based on 20 CES-D items, such as "I was bothered by things that usually don't bother me" and "I did not feel like eating, my appetite was poor". Patients were asked to answer each item by 4 scales: (1) Rarely, (2) Sometimes, (3) Occasionally, and (4) Most of the time. After 4 negative items were multiplied by -1, the total CES-D score is a simple sum of all items.

The min and Max are 0 and 60, respectively. Higher scores indicate more severe depressive symptoms.

Enrollment:	73
Study Start Date:	April 2008
Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Minocycline Minocycline 100 mg orally every 12 hours	Drug: minocycline 100 mg capsule every 12 hours by mouth
Placebo Comparator: Placebo Placebo minocycline capsules every 12 hours	Drug: minocycline placebo capsule 1 capsule every 12 hours by mouth

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV infection prior to study entry
Naïve to any antiretroviral regimen and ineligible to receive antiretroviral therapy by cluster of differentiation 4 (CD4) criteria in Uganda
Negative serum or urine pregnancy test for women of childbearing potential
Willingness to use birth control
Age 18-65 years
AIDS Dementia Scale Stage 0.5 OR 1
Impaired cognitive performance as evidenced by an International HIV Dementia Scale (HDS) as defined by the protocol
Ability to sit or stand and swallow intact capsules with an 8-ounce glass of water
Ability and willingness of subject or legal guardian/ representative to give written informed consent
Resident within a 20km radius of Kampala city

Exclusion Criteria:

Current cancers other than basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or which does not require systemic chemotherapy
Severe premorbid psychiatric illness, including schizophrenia and major depression which, in the in investigator's opinion, is likely to interfere with study compliance
Active symptomatic AIDS-defining opportunistic infection within 45 days prior to study entry
Confounding neurological disorders as defined in the protocol
Central nervous system infections or cancers as defined in the protocol
Systemic lupus
Thyroid disease diagnosed within 24 weeks prior to entry
Breastfeeding
Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator
History of allergy/sensitivity to minocycline or other tetracyclines and their formulations
Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the subject's ability to participate in the study. This includes an individual found to have an HIV dementia scale stage 3 or 4.
Any esophageal or other condition that would interfere with the swallowing of the study medication
Use of excluded drugs as defined by the protocol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00855062

Locations

Uganda
Infecious Diseas Institute
Kampala, Uganda

Sponsors and Collaborators

Johns Hopkins University

Makerere University

Investigators

Principal Investigator:

Ned Sacktor, MD

Johns Hopkins School of Medicine

More Information

Additional Information:

Website of NARC, the sponsoring grant for this trial This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Ned Sacktor, MD, Johns Hopkins School of Medicine
ClinicalTrials.gov Identifier:	NCT00855062 History of Changes
Other Study ID Numbers:	Uganda minocycline study, Grant Number: 5 UO1 NS32228
Study First Received:	March 2, 2009
Results First Received:	December 17, 2010
Last Updated:	January 28, 2011
Health Authority:	United States: Federal Government; United States: NINDS appointed Data Safety Monitoring Committee for the Neurologic AIDS Research Consortium

Keywords provided by Johns Hopkins University:

Human immunodeficiency virus (HIV)
HIV associated cognitive impairment
HIV dementia

Uganda
Acquired immune deficiency syndrome (AIDS)
Treatment Naive

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Cognition Disorders
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes

Immune System Diseases
Slow Virus Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012