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Combination Therapy for the Treatment of Bipolar Disorders

Primary Purpose

Bipolar Disorder

Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Lithium
Lamotrigine
Divalproex
Placebo
Sponsored by
University Hospitals Cleveland Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Disorder focused on measuring Depression

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Bipolar I or II Disorder Meet criteria for rapid cycling, defined as four or more episodes over the past 12 months Meet criteria for a major depressive episode Exclusion Criteria: History of intolerability of lithium, divalproex, or lamotrigine

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Lithium + divalproex + lamotrigine

    Lithium + divalproex + placebo

    Arm Description

    Outcomes

    Primary Outcome Measures

    The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response
    A marked bimodal response is defined by the following three conditions over four consecutive weeks while on triple therapy and after three weeks of ltg: Montgomery Asberg Depression Rating Scale (MADRS) total score of <= 19 Young Mania Rating Scale (YMRS) total score of <= 12.5 Global Assessment Scale (GAS) score >= 51 The MADRS measures the severity of a subject's depression symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe depression. The YMRS measures the severity of a subject's manic symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe mania. The GAS measures a used to rate subjectively the social, occupational, and psychological functioning of a subject and ranges in score from 0-100, with a higher score indicating better social, occupational, and psychological functioning.

    Secondary Outcome Measures

    Full Information

    First Posted
    June 25, 2003
    Last Updated
    October 3, 2016
    Sponsor
    University Hospitals Cleveland Medical Center
    Collaborators
    National Institute of Mental Health (NIMH)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00063362
    Brief Title
    Combination Therapy for the Treatment of Bipolar Disorders
    Official Title
    Combination Therapy in Bipolar Rapid Cycling
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2016
    Overall Recruitment Status
    Terminated
    Why Stopped
    Funding Expiration
    Study Start Date
    February 2002 (undefined)
    Primary Completion Date
    July 2007 (Actual)
    Study Completion Date
    July 2007 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University Hospitals Cleveland Medical Center
    Collaborators
    National Institute of Mental Health (NIMH)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study will compare triple and double drug regimens in the treatment of patients with depression, hypomania, or mania.
    Detailed Description
    Early studies have shown lithium to produce a high percentage of satisfactory clinical response in patients with bipolar disorders. These studies, however, do not include lithium-refractory subgroups, such as bipolar II disorder patients. When the wide spectrum of bipolar disorders is considered, the lithium response rate decreases significantly. More broadly effective regimens are needed. Participants in this study will be randomly assigned to receive either lithium plus divalproex or lithium, divalproex, and lamotrigine for 7 months. Symptoms of depression and mania will be assessed with scales and patient questionnaires.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Bipolar Disorder
    Keywords
    Depression

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    49 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Lithium + divalproex + lamotrigine
    Arm Type
    Experimental
    Arm Title
    Lithium + divalproex + placebo
    Arm Type
    Placebo Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Lithium
    Other Intervention Name(s)
    Lithium Carbonate
    Intervention Description
    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).
    Intervention Type
    Drug
    Intervention Name(s)
    Lamotrigine
    Other Intervention Name(s)
    Lamictal
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Divalproex
    Other Intervention Name(s)
    Depakote, Valproic Acid
    Intervention Description
    Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response
    Description
    A marked bimodal response is defined by the following three conditions over four consecutive weeks while on triple therapy and after three weeks of ltg: Montgomery Asberg Depression Rating Scale (MADRS) total score of <= 19 Young Mania Rating Scale (YMRS) total score of <= 12.5 Global Assessment Scale (GAS) score >= 51 The MADRS measures the severity of a subject's depression symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe depression. The YMRS measures the severity of a subject's manic symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe mania. The GAS measures a used to rate subjectively the social, occupational, and psychological functioning of a subject and ranges in score from 0-100, with a higher score indicating better social, occupational, and psychological functioning.
    Time Frame
    Baseline and Week 28

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    16 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Bipolar I or II Disorder Meet criteria for rapid cycling, defined as four or more episodes over the past 12 months Meet criteria for a major depressive episode Exclusion Criteria: History of intolerability of lithium, divalproex, or lamotrigine
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Keming Gao, MD, PhD
    Organizational Affiliation
    Case Western Reserve University / University Hospitals of Cleveland
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Combination Therapy for the Treatment of Bipolar Disorders

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