Combination Therapy for the Treatment of Bipolar Disorders

NCT00063362 | Terminated Phase 3 Results DMC

• 2 other identifiers: R21MH062650DSIR AT-SO
• Study Type: interventional
• Target: 49
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will compare triple and double drug regimens in the treatment of patients with depression, hypomania, or mania.

Conditions

Bipolar Disorder

Keywords

Depression

Outcome Measures

Primary Outcomes (1)

• 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: 1. Montgomery Asberg Depression Rating Scale (MADRS) total score of \<= 19 2. Young Mania Rating Scale (YMRS) total score of \<= 12.5 3. 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.

  Baseline and Week 28

Study Arms (2)

Lithium + divalproex + lamotrigine

EXPERIMENTAL

Drug: Lithium; Drug: Lamotrigine; Drug: Divalproex

Lithium + divalproex + placebo

PLACEBO COMPARATOR

Drug: Lithium; Drug: Divalproex; Drug: Placebo

Interventions

Lithium DRUG

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).

Also known as: Lithium Carbonate

Lithium + divalproex + lamotrigine; Lithium + divalproex + placebo

Lamotrigine DRUG

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.

Also known as: Lamictal

Lithium + divalproex + lamotrigine

Divalproex DRUG

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

Also known as: Depakote, Valproic Acid

Lithium + divalproex + lamotrigine; Lithium + divalproex + placebo

Placebo DRUG

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 + divalproex + placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• History of intolerability of lithium, divalproex, or lamotrigine

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• National Institute of Mental Health (NIMH): collaborator

MeSH Terms

Conditions

Bipolar Disorder; Depression

Interventions

Lithium; Lithium Carbonate; Lamotrigine; Valproic Acid

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Keming Gao
• Organization: University Hospitals Case Medical Center

keming.gao@UHhospitals.org

216-844-2865

Study Officials

• Keming Gao, MD, PhD

  Case Western Reserve University / University Hospitals of Cleveland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Mood and Anxiety Clinic

Study Record Dates

• First Submitted: June 25, 2003
• First Posted: June 27, 2003
• Study Start: February 1, 2002
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: November 7, 2016
• Results First Posted: January 30, 2014

Record last verified: 2016-10