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Citalopram for Agitation in Alzheimer's Disease (CitAD)

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ClinicalTrials.gov Identifier: NCT00898807
Recruitment Status : Completed
First Posted : May 12, 2009
Results First Posted : June 27, 2014
Last Update Posted : June 27, 2014
Sponsor:
Collaborators:
National Institute on Aging (NIA)
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Dave Shade, Johns Hopkins University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Alzheimer's Disease
Agitation
Interventions Drug: citalopram
Drug: placebo
Enrollment 186
Recruitment Details Recruitment activities included chart review, telephone interviews and screens, discussion with physicians, and recruitment in the clinic waiting areas and assisted living facilities affiliated with the clinics. The recruitment period lasted from August 2009 to December 2012.
Pre-assignment Details  
Arm/Group Title Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention
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Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention

citalopram : target dose 30mg daily for 9 weeks

Matching placebo, oral, and psychosocial intervention

placebo : daily for 9 weeks

Period Title: Overall Study
Started 94 92
Completed 86 83
Not Completed 8 9
Reason Not Completed
Withdrawal by Subject             5             3
Family pressure to discontinue             2             2
Lost to Follow-up             1             3
Death             0             1
Arm/Group Title Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention Total
Hide Arm/Group Description

Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention

citalopram : target dose 30mg daily for 9 weeks

Matching placebo, oral, and psychosocial intervention

placebo : daily for 9 weeks

Total of all reporting groups
Overall Number of Baseline Participants 94 92 186
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 94 participants 92 participants 186 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
   6.4%
7
   7.6%
13
   7.0%
>=65 years
88
  93.6%
85
  92.4%
173
  93.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 94 participants 92 participants 186 participants
78  (9) 79  (8) 78  (8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 94 participants 92 participants 186 participants
Female
44
  46.8%
41
  44.6%
85
  45.7%
Male
50
  53.2%
51
  55.4%
101
  54.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 94 participants 92 participants 186 participants
United States 82 79 161
Canada 12 13 25
1.Primary Outcome
Title NeuroBehavior Rating Scale-- Agitation
Hide Description NeuroBehavioral Rating Scale- Agitation(NBRS-A) assesses multiple types of psychopathology common in dementia and is based on a seven point Likert scale of increasing severity for each item(i.e., 0=not present, 1=very mild, 2-mild, 3=moderate, 4=moderately severe, 5=severe, 6=extremely severe). The NBRS agitation subscore includes NBRS 'inhibition’, ‘agitation’, and ‘hostility’. The range is 0 to 18 points. Higher scores indicate more symptoms.
Time Frame 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was an intention-to-treat analysis; analysis was conducted "as randomized". Data from the 186 randomized participants were used in the analytic model. 167 of the 186 patients had week 9 data on the NBRS.
Arm/Group Title Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention
Hide Arm/Group Description:

Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention

citalopram : target dose 30mg daily for 9 weeks

Matching placebo, oral, and psychosocial intervention

placebo : daily for 9 weeks

Overall Number of Participants Analyzed 90 85
Mean (Standard Error)
Unit of Measure: units on a scale
4.33  (0.31) 5.26  (0.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Citalopram and Psychosocial Intervention, Placebo and Psychosocial Intervention
Comments Primary assessment of efficacy was based on intention-to-treat comparison of the difference in the NBRS-A scores at week 9 and comparison at week 9 for the CGIC. For the NBRS-A, the study was designed to have 85% power to detect a standardized difference at week 9 of 40% for citalopram compared to placebo at week 9.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments P-value was not adjusted for multiple comparisons. All p-values are two-sided and p<0.05 was the threshold for statistical significance.
Method Mixed Models Analysis
Comments Mixed effects model w/ random intercept for patient, visit indicator, treatment by visit interactions and adjusted for baseline NBRS-A & cognition.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.93
Confidence Interval (2-Sided) 95%
-1.80 to -0.06
Estimation Comments Negative numbers favor citalopram group.
2.Primary Outcome
Title Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change in Agitation(CGIC)
Hide Description Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change in agitation(CGIC) accesses clinically significant change in agitation. A trained clinician, blind to treatment assignment, uses a 7-point Likert scale to rate change of each patient along a continuum from “marked improvement”(1), “no change”(4), and “marked worsening”(7). A number of aspects of the agitation is considered such as emotional agitation, mood liability/distress, psychomotor agitation, verbal aggression, and physical aggression. Range is 1-7.
Time Frame Baseline to 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was an intention-to-treat analysis; analysis was conducted "as randomized". Data from the 186 randomized participants were used in the analytic model. 167 of the 186 patients had week 9 data on CGIC.
Arm/Group Title Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention
Hide Arm/Group Description:

Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention

citalopram : target dose 30mg daily for 9 weeks

Matching placebo, oral, and psychosocial intervention

placebo : daily for 9 weeks

Overall Number of Participants Analyzed 86 81
Measure Type: Number
Unit of Measure: percentage moderate/marked improvement
40 26
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Citalopram and Psychosocial Intervention, Placebo and Psychosocial Intervention
Comments Primary assessment of efficacy was based on intention-to-treat comparison of the difference in the NBRS-A scores at week 9 and comparison at week 9 for the CGIC. For the CGIC proportional odds analysis, the study was designed to have power greater than 80% to detect a difference of 20% between citalopram and placebo in the proportions of patients who improve (or worsen).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments All p-values are two-sided and p <0.05 was the threshold for statistical significance. No adjustments were made for multiple comparisons.
Method Proportional odds
Comments estimated treatment effect from the proportional odds model
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.13
Confidence Interval (2-Sided) 95%
1.23 to 3.69
Estimation Comments Positive numbers favors citalopram.
3.Secondary Outcome
Title Cohen-Mansfield Agitation Inventory (CMAI)
Hide Description CMAI examines several agitated behaviors including verbal, physical agitation, and other behaviors. Sub-items are summed. Range is 14-70. Higher scores indicate more severe symptoms.
Time Frame 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was an intention-to-treat analysis; analysis was conducted "as randomized". Data from the 186 randomized participants were used in the analytic model. 169 of the 186 patients had week 9 data.
Arm/Group Title Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention
Hide Arm/Group Description:

Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention

citalopram : target dose 30mg daily for 9 weeks

Matching placebo, oral, and psychosocial intervention

placebo : daily for 9 weeks

Overall Number of Participants Analyzed 90 85
Mean (Standard Deviation)
Unit of Measure: units on a scale
27.7  (6.7) 28.7  (6.7)
4.Secondary Outcome
Title Neuropsychiatric Inventory (NPI)-- Agitation Subscore
Hide Description NPI agitation score is based on responses from an informed caregiver involved in the patient's life. Symptom severity (1=mild, 2=moderate, 3=severe) is multiplied by frequency (1=occasionally, less than once/week; 4 = very frequently, once or more/day or continuously) to obtain the NPI agitation score.Range is 0-12. Higher scores indicate more severe symptoms.
Time Frame 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was an intention-to-treat analysis; analysis was conducted "as randomized". Data from the 186 randomized participants were used in the analytic model. 169 of the 186 patients had week 9 data.
Arm/Group Title Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention
Hide Arm/Group Description:

Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention

citalopram : target dose 30mg daily for 9 weeks

Matching placebo, oral, and psychosocial intervention

placebo : daily for 9 weeks

Overall Number of Participants Analyzed 90 85
Mean (Standard Deviation)
Unit of Measure: units on a scale
7.8  (2.2) 8.0  (2.4)
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
 
Arm/Group Title Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention
Hide Arm/Group Description

Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention

citalopram : target dose 30mg daily for 9 weeks

Matching placebo, oral, and psychosocial intervention

placebo : daily for 9 weeks

All-Cause Mortality
Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention
Affected / at Risk (%) Affected / at Risk (%)
Total   8/94 (8.51%)   7/92 (7.61%) 
Cardiac disorders     
Hypotension *  1/94 (1.06%)  0/92 (0.00%) 
Chest pain *  1/94 (1.06%)  0/92 (0.00%) 
Infections and infestations     
Sepsis *  1/94 (1.06%)  0/92 (0.00%) 
Surgical removal of infected plate in wrist *  1/94 (1.06%)  0/92 (0.00%) 
Musculoskeletal and connective tissue disorders     
Abdominal pain *  0/94 (0.00%)  1/92 (1.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung cancer *  0/94 (0.00%)  1/92 (1.09%) 
Nervous system disorders     
Fall *  1/94 (1.06%)  1/92 (1.09%) 
Psychiatric disorders     
Mental status change *  1/94 (1.06%)  2/92 (2.17%) 
Increased agitation *  1/94 (1.06%)  2/92 (2.17%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia *  1/94 (1.06%)  0/92 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Citalopram and Psychosocial Intervention Placebo and Psychosocial Intervention
Affected / at Risk (%) Affected / at Risk (%)
Total   90/90 (100.00%)   86/86 (100.00%) 
Gastrointestinal disorders     
Abdominal pain   14/90 (15.56%)  19/86 (22.09%) 
Anorexia   40/90 (44.44%)  26/86 (30.23%) 
Nausea   5/90 (5.56%)  6/86 (6.98%) 
Diarrhea   25/90 (27.78%)  12/86 (13.95%) 
Dry mouth   21/90 (23.33%)  24/86 (27.91%) 
Indigestion   23/90 (25.56%)  18/86 (20.93%) 
Constipation   13/90 (14.44%)  22/86 (25.58%) 
Vomiting   5/90 (5.56%)  0/86 (0.00%) 
General disorders     
Fatigue   54/90 (60.00%)  53/86 (61.63%) 
Drug allergy   4/90 (4.44%)  4/86 (4.65%) 
Infections and infestations     
Fever   9/90 (10.00%)  2/86 (2.33%) 
Musculoskeletal and connective tissue disorders     
Asthenia   29/90 (32.22%)  30/86 (34.88%) 
Muscle pain   29/90 (32.22%)  34/86 (39.53%) 
Joint pain   40/90 (44.44%)  48/86 (55.81%) 
Nervous system disorders     
Sweating   9/90 (10.00%)  12/86 (13.95%) 
Tremor   23/90 (25.56%)  16/86 (18.60%) 
Dizziness   22/90 (24.44%)  19/86 (22.09%) 
Gait instability   50/90 (55.56%)  44/86 (51.16%) 
Yawning   11/90 (12.22%)  17/86 (19.77%) 
Falls   15/90 (16.67%)  10/86 (11.63%) 
Headache   21/90 (23.33%)  18/86 (20.93%) 
Visual disturbance   12/90 (13.33%)  14/86 (16.28%) 
Psychiatric disorders     
Somnolence   47/90 (52.22%)  42/86 (48.84%) 
Insomnia   28/90 (31.11%)  39/86 (45.35%) 
Anxiety   65/90 (72.22%)  66/86 (76.74%) 
Deceased libido   14/90 (15.56%)  18/86 (20.93%) 
Confusion   69/90 (76.67%)  72/86 (83.72%) 
Suicidal thoughts   6/90 (6.67%)  4/86 (4.65%) 
Reproductive system and breast disorders     
Ejaculatory dysfunction   6/48 (12.50%)  3/48 (6.25%) 
Respiratory, thoracic and mediastinal disorders     
Upper respiratory infection   17/90 (18.89%)  9/86 (10.47%) 
Rhinitis   33/90 (36.67%)  30/86 (34.88%) 
Pneumonia   1/90 (1.11%)  0/86 (0.00%) 
Cough   27/90 (30.00%)  26/86 (30.23%) 
Bronchitis   3/90 (3.33%)  2/86 (2.33%) 
Nasal congestion   22/90 (24.44%)  22/86 (25.58%) 
Sore throat   7/90 (7.78%)  7/86 (8.14%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Anne Casper
Organization: Johns Hopkins
Phone: 410-955-8183
Responsible Party: Dave Shade, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00898807     History of Changes
Other Study ID Numbers: IA0155
R01AG031348 ( U.S. NIH Grant/Contract )
First Submitted: May 11, 2009
First Posted: May 12, 2009
Results First Submitted: March 19, 2014
Results First Posted: June 27, 2014
Last Update Posted: June 27, 2014