Combination Therapy for the Treatment of Bipolar Disorders

This study has been terminated.
(Funding Expiration)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dr. Keming Gao, University Hospital Case Medical Center
ClinicalTrials.gov Identifier:
NCT00063362
First received: June 25, 2003
Last updated: December 23, 2013
Last verified: December 2013
Results First Received: November 4, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Bipolar Disorder
Interventions: Drug: Lithium
Drug: Lamotrigine
Drug: Divalproex
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted by the Mood Disorders Program at Case Western Reserve University/University Hospitals Case Medical Center (Cleveland, OH, USA) from August 2002 to June 2007.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Lithium + Divalproex + Lamotrigine

Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.

Lamotrigine : Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum.

dose of 200 mg per day.

Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 milliequivalent/L (mEq/L).

Lithium + Divalproex + Placebo

Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.

Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.


Participant Flow:   Overall Study
    Lithium + Divalproex + Lamotrigine     Lithium + Divalproex + Placebo  
STARTED     23     26  
COMPLETED     19     22  
NOT COMPLETED     4     4  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Lithium + Divalproex + Lamotrigine

Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.

Lamotrigine : Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum.

dose of 200 mg per day.

Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.

Lithium + Divalproex + Placebo

Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.

Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.

Total Total of all reporting groups

Baseline Measures
    Lithium + Divalproex + Lamotrigine     Lithium + Divalproex + Placebo     Total  
Number of Participants  
[units: participants]
  23     26     49  
Age  
[units: years]
Mean ± Standard Deviation
  35.7  ± 11.0     43.0  ± 9.6     37.9  ± 11.1  
Gender  
[units: participants]
     
Female     12     15     27  
Male     11     11     22  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     2     2     4  
White     21     24     45  
More than one race     0     0     0  
Unknown or Not Reported     0     0     0  
Bipolar Subtype [1]
[units: participants]
     
Bipolar I disorder     11     16     27  
Bipolar II disorder     12     10     22  
[1]

Bipolar I Disorder is mainly defined by manic or mixed episodes that last at least seven days, or by manic symptoms that are so severe that the person needs immediate hospital care.

Bipolar II Disorder is defined by a pattern of depressive episodes shifting back and forth with hypomanic episodes, but no full manic or mixed episodes




  Outcome Measures

1.  Primary:   The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response   [ Time Frame: Baseline and Week 28 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Dr. Keming Gao
Organization: University Hospitals Case Medical Center
phone: 216-844-2865
e-mail: keming.gao@UHhospitals.org


No publications provided


Responsible Party: Dr. Keming Gao, University Hospital Case Medical Center
ClinicalTrials.gov Identifier: NCT00063362     History of Changes
Other Study ID Numbers: R21 MH62650, R21MH062650, DSIR AT-SO
Study First Received: June 25, 2003
Results First Received: November 4, 2013
Last Updated: December 23, 2013
Health Authority: United States: Food and Drug Administration