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Riluzole to Treat Depression in Bipolar Disorder

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ClinicalTrials.gov Identifier: NCT00054704
Recruitment Status : Terminated (Placebo was better than active drug.)
First Posted : February 7, 2003
Results First Posted : May 2, 2016
Last Update Posted : May 19, 2016
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Treatment
Condition Bipolar Disorder
Interventions Drug: Riluzole
Drug: Placebo
Enrollment 20
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Riluzole Placebo
Hide Arm/Group Description Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study. Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.
Period Title: Overall Study
Started 9 11
Completed 4 6
Not Completed 5 5
Reason Not Completed
Lack of Efficacy             1             3
Adverse Event             3             2
Lost to Follow-up             1             0
Arm/Group Title Riluzole Placebo Total
Hide Arm/Group Description Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study. Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study. Total of all reporting groups
Overall Number of Baseline Participants 9 11 20
Hide Baseline Analysis Population Description
All participants randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 11 participants 20 participants
46.78  (15.14) 48.27  (11.15) 47.60  (12.75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 11 participants 20 participants
Female
1
  11.1%
5
  45.5%
6
  30.0%
Male
8
  88.9%
6
  54.5%
14
  70.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 9 participants 11 participants 20 participants
9 11 20
1.Primary Outcome
Title Montgomery-Asberg Depression Rating Scale
Hide Description The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-rated assessment of depression symptoms. Patients were rated weekly on 10 symptoms on a scale of 0 to 6 for each item, where 0 indicated no symptoms and 6 indicated the highest severity of that symptom. Total scores range from 0 to 60, where a moderate severity of depression would be present with a score of at least 20.
Time Frame 8 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data from all patients were included in the analysis.
Arm/Group Title Riluzole Placebo
Hide Arm/Group Description:
Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.
Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.
Overall Number of Participants Analyzed 9 11
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
29.551  (2.481) 23.723  (1.916)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riluzole, Placebo
Comments The primary intent of this study was to compare the efficacy of riluzole to placebo in the treatment of overall depressive symptomatology of bipolar disorder subjects who were acutely depressed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .086
Comments A linear mixed model included drug, visit and their interaction as fixed factors. Subject was a random factor. The test here is for the main effect of drug.
Method Mixed Models Analysis
Comments Baseline score was a covariate. Restricted maximum likelihood estimates were used with a compound symmetry covariance structure.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.828
Confidence Interval (2-Sided) 95%
-12.590 to 0.934
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.182
Estimation Comments Significant omnibus effects were examined using Bonferroni post hoc tests.
Time Frame Adverse event data was collected systematically on a weekly basis throughout the course of the study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Riluzole Placebo
Hide Arm/Group Description Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study. Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.
All-Cause Mortality
Riluzole Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Riluzole Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/9 (0.00%)      0/11 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Riluzole Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/9 (88.89%)      8/11 (72.73%)    
Gastrointestinal disorders     
Gastrointestinal Problems   5/9 (55.56%)  5 1/11 (9.09%)  1
General disorders     
Dizziness   3/9 (33.33%)  3 0/11 (0.00%)  0
Headache   1/9 (11.11%)  1 2/11 (18.18%)  2
Dry mouth   1/9 (11.11%)  1 1/11 (9.09%)  1
Sleep problems   5/9 (55.56%)  5 4/11 (36.36%)  4
Memory problems   2/9 (22.22%)  2 1/11 (9.09%)  1
Concentration difficulty   3/9 (33.33%)  3 2/11 (18.18%)  2
Fatigue   3/9 (33.33%)  3 2/11 (18.18%)  2
Musculoskeletal and connective tissue disorders     
Muscle, joint, or bone pain   2/9 (22.22%)  2 1/11 (9.09%)  1
Psychiatric disorders     
Suicidal ideation   2/9 (22.22%)  2 1/11 (9.09%)  1
Reproductive system and breast disorders     
Decreased libido   2/9 (22.22%)  2 3/11 (27.27%)  3
Respiratory, thoracic and mediastinal disorders     
Coughing   1/9 (11.11%)  1 3/11 (27.27%)  3
Nasal and throat problems   3/9 (33.33%)  3 3/11 (27.27%)  3
Skin and subcutaneous tissue disorders     
Skin irritation   1/9 (11.11%)  1 1/11 (9.09%)  1
Indicates events were collected by systematic assessment
The study was terminated due to results suggesting the active drug was leading to worse outcomes than placebo.
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: Dr. Carlos Zarate
Organization: NIMH, DIRP, Experimental Therapeutics and Pathophysiology Branch
Phone: 3014510861
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier: NCT00054704     History of Changes
Other Study ID Numbers: 030092
03-M-0092 ( Other Identifier: NIH CNS IRB )
First Submitted: February 6, 2003
First Posted: February 7, 2003
Results First Submitted: December 10, 2015
Results First Posted: May 2, 2016
Last Update Posted: May 19, 2016