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Levetiracetam in the Management of Bipolar Depression

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ClinicalTrials.gov Identifier: NCT00566150
Recruitment Status : Completed
First Posted : December 3, 2007
Results First Posted : November 2, 2015
Last Update Posted : September 30, 2016
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by (Responsible Party):
Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Bipolar Depression
Interventions Drug: Levetiracetam
Drug: Placebo
Enrollment 35
Recruitment Details Subjects were recruited from 2005-2008 from New Haven, CT and surrounding areas.
Pre-assignment Details  
Arm/Group Title Levetiracetam Placebo
Hide Arm/Group Description Subjects on active study medication. Subjects assigned to placebo control group.
Period Title: Overall Study
Started 19 16
Completed 10 11
Not Completed 9 5
Arm/Group Title Levetiracetam Placebo Total
Hide Arm/Group Description Subjects on active study medication. Subjects assigned to placebo control group. Total of all reporting groups
Overall Number of Baseline Participants 19 16 35
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 16 participants 35 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
19
 100.0%
16
 100.0%
35
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 16 participants 35 participants
45.5  (10.7) 42.4  (9.6) 44.1  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 16 participants 35 participants
Female
11
  57.9%
9
  56.3%
20
  57.1%
Male
8
  42.1%
7
  43.8%
15
  42.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants 16 participants 35 participants
19 16 35
1.Primary Outcome
Title Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6.
Hide Description Change is observed value at each visit minus baseline value. HDRS-21 is a 21-item instrument measuring depression. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 60.
Time Frame Baseline to week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Weeks 1-6 are Intent to treat (ITT) population Observed Cases. All participants included received at least 1 dose of study intervention and at least 1 assessment post-baseline.
Arm/Group Title Levetiracetam Placebo
Hide Arm/Group Description:
Subjects on active study medication.
Subjects assigned to placebo control group.
Overall Number of Participants Analyzed 17 15
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
Week 1 (n=17, n=15) -2.7647  (1.4138) -4  (1.5051)
Week 2 (n=15, n=14) -3.4259  (1.4618) -6.5875  (1.5327)
Week 3 (n=13, n=14) -2.1243  (1.5441) -6.3625  (1.5458)
Week 4 (n=11, n=13) -4.3534  (1.6582) -6.3851  (1.583)
Week 5 (n=11, n=13) -6.952  (1.7105) -6.4368  (1.6006)
Week 6 (n=10, n=11) -4.8136  (1.7806) -7.0712  (1.6838)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Placebo
Comments Comparison of changes in outcome between treatment groups at week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.29
Comments Unadjusted. Statistical significance was p<0.05.
Method Mixed Models Analysis
Comments Fixed categorical effects: group (as a between-subjects factor), time (as a within-subjects factor), group x time interaction.
2.Secondary Outcome
Title Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6.
Hide Description Change is observed value at each visit minus baseline value. MADRS is a 10-item instrument measuring depression: scale range between 0(normal) - 6(most abnormal)for each item. Total possible score is 0 - 60.
Time Frame Baseline to week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Weeks 1-6 are Intent to treat (ITT) population Observed Cases. All participants included received at least 1 dose of study intervention and at least 1 assessment post-baseline.
Arm/Group Title Levetiracetam Placebo
Hide Arm/Group Description:
Subjects on active study medication.
Subjects assigned to placebo control group.
Overall Number of Participants Analyzed 17 15
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
Week 1 (n=17, n=15) -3.2941  (2.0145) -2.7333  (2.1446)
Week 2 (n=15, n=14) -5.2319  (2.1105) -7.256  (2.1999)
Week 3 (n=13, n=14) -3.384  (2.2162) -9.0417  (2.1999)
Week 4 (n=11, n=13) -5.5505  (2.3441) -8.7608  (2.2514)
Week 5 (n=11, n=12) -9.9142  (2.3441) -6.6591  (2.3061)
Week 6 (n=10, n=11) -6.5208  (2.4183) -4.5153  (2.3691)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Placebo
Comments Comparison of changes in outcome between treatment groups at week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments Unadjusted. Statistical significance was p<0.05.
Method Mixed Models Analysis
Comments Fixed categorical effects: group (as a between-subjects factor), time (as a within-subjects factor), group x time interaction.
3.Secondary Outcome
Title Number of Subjects Who Achieve Remission.
Hide Description

Remission response is measured as an HDRS-21 total score is less than or equal to 7.

HDRS-21 measures range of depressive symptoms. Endpoint is LOCF.

Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Placebo
Hide Arm/Group Description:
Subjects on active study medication.
Subjects assigned to placebo control group.
Overall Number of Participants Analyzed 17 15
Measure Type: Number
Unit of Measure: Participants
Remitted 0 4
Not remitted 17 11
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Placebo
Comments Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .038
Comments Statistical significance was p<0.05
Method Fisher Exact
Comments Fisher's exact test was used to test for significance between groups.
4.Secondary Outcome
Title Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6.
Hide Description Change is observed value at each visit minus baseline value. CGI-BP depression severity is an instrument which measures severity of depression in bipolar disorder. Scale range: 1=normal, not ill; 7=very severely ill
Time Frame Baseline to week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Weeks 1-6 are Intent to treat (ITT) population Observed Cases. All participants included received at least 1 dose of study intervention and at least 1 assessment post-baseline.
Arm/Group Title Levetiracetam Placebo
Hide Arm/Group Description:
Subjects on active study medication.
Subjects assigned to placebo control group.
Overall Number of Participants Analyzed 17 15
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
Week 1 (n=17, n=15) -0.2941  (0.1982) -0.4667  (0.211)
Week 2 (n=14, n=14) -0.3186  (0.211) -0.6956  (0.2161)
Week 3 (n=13, n=14) -0.1984  (0.2207) -0.7753  (0.2177)
Week 4 (n=11, n=13) -0.3729  (0.2386) -0.8403  (0.2238)
Week 5 (n=11, n=12) -0.7325  (0.244) -0.8739  (0.2322)
Week 6 (n=10, n=10) -0.5742  (0.2539) -0.9294  (0.2505)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Placebo
Comments Comparison of changes in outcome between treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments Unadjusted. Statistical significance was p<0.05.
Method Mixed Models Analysis
Comments Fixed categorical effects: group (as a between-subjects factor), time (as a within-subjects factor), group x time interaction.
Time Frame Adverse events were collected during course of the study and for two weeks after last study intervention.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Levetiracetam Placebo
Hide Arm/Group Description Subjects on active study medication. Subjects assigned to placebo control group.
All-Cause Mortality
Levetiracetam Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Levetiracetam Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)   0/16 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Levetiracetam Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   17/19 (89.47%)   15/16 (93.75%) 
Cardiac disorders     
Cardiac *  0/19 (0.00%)  1/16 (6.25%) 
Gastrointestinal disorders     
GI symptoms *  6/19 (31.58%)  5/16 (31.25%) 
Dry mouth *  2/19 (10.53%)  2/16 (12.50%) 
Drooling *  1/19 (5.26%)  0/16 (0.00%) 
Taste *  0/19 (0.00%)  1/16 (6.25%) 
General disorders     
Genitourinary *  1/19 (5.26%)  0/16 (0.00%) 
Unusual dreams/nightmares *  0/19 (0.00%)  1/16 (6.25%) 
Nosebleed *  0/19 (0.00%)  1/16 (6.25%) 
Cold *  0/19 (0.00%)  2/16 (12.50%) 
Musculoskeletal and connective tissue disorders     
Rash *  0/19 (0.00%)  1/16 (6.25%) 
Muscle soreness *  0/19 (0.00%)  1/16 (6.25%) 
Nervous system disorders     
Somnolence *  10/19 (52.63%)  7/16 (43.75%) 
Coordination *  4/19 (21.05%)  0/16 (0.00%) 
Shakiness *  2/19 (10.53%)  2/16 (12.50%) 
Dizziness *  3/19 (15.79%)  2/16 (12.50%) 
Weakness *  3/19 (15.79%)  0/16 (0.00%) 
Headache *  3/19 (15.79%)  6/16 (37.50%) 
Slurred speech *  1/19 (5.26%)  0/16 (0.00%) 
Blurred vision *  0/19 (0.00%)  1/16 (6.25%) 
Psychiatric disorders     
Irritability *  5/19 (26.32%)  1/16 (6.25%) 
Hypomanic symptoms *  2/19 (10.53%)  0/16 (0.00%) 
Worsening of depressive symptoms *  2/19 (10.53%)  1/16 (6.25%) 
Insomnia *  1/19 (5.26%)  1/16 (6.25%) 
Sunstance Abuse Relapse *  2/19 (10.53%)  1/16 (6.25%) 
Increase in suicidality *  1/19 (5.26%)  0/16 (0.00%) 
Cognitive *  1/19 (5.26%)  1/16 (6.25%) 
*
Indicates events were collected by non-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
Layout table for Results Point of Contact information
Name/Title: Dr. Zubin Bhagwagar
Organization: Yale University
Phone: 203-974-7560
EMail: zubin.bhagwagar@yale.edu
Layout table for additonal information
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00566150     History of Changes
Other Study ID Numbers: 05T-681
HIC#0508000506 ( Other Identifier: Yale University IRB )
First Submitted: November 29, 2007
First Posted: December 3, 2007
Results First Submitted: October 2, 2009
Results First Posted: November 2, 2015
Last Update Posted: September 30, 2016