Sequential Multiple Assignment Treatment for Bipolar Disorder

NCT01588457 | Completed Phase 4 Results DMC

• 2 other identifiers: HSC20110361H1P30MH086045-01A2
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to compare which of the two mood stabilizers (drugs that help to steady/stabilize mood in patients with bipolar disorder (BD)), lithium and divalproex, is more effective in patients with bipolar disorder over 26 weeks. The study will also compare if lithium or divalproex used alone versus lithium or divalproex used with quetiapine versus lithium or divalproex used with lamotrigine is more effective when symptoms of depression develop.

Conditions

Bipolar I Disorder; Bipolar II Disorder

Outcome Measures

Primary Outcomes (1)

• Bipolar Inventory of Symptoms Scale (BISS)

  The BISS uses a structured interview to assess the full spectrum of symptoms associated with all primary clinical states in bipolar disorder, yielding a total severity, a depression, a mania, as well as dimensional scale scores. There are 42 items; each item is rated on a 0-4 scale. The BISS is a clinician-rated instrument. The Scale is rated as follows: 0 Not at all 1. Slight 2. Mild 3. Moderate 4. Severe Each of the 42 items is rated separately, with a score, based on the most recent 7 day period. The mean score is calculated from the total score, giving an overall score out of 4, where 0 is slight and 4 is the most severe symptoms. A negative score indicated an improvement from baseline to 26 weeks.

  Change from Baseline to 26 weeks

Secondary Outcomes (3)

• Global Assessment of Functioning

  Change from Baseline to 26 weeks

• Baseline Randomization Percentage of Bipolar Types

  Baseline

• Demographic in Randomization 1 Group

  Baseline

Study Arms (6)

Lithium

ACTIVE COMPARATOR

This open methods advancement study will randomize BD patients with clinically significant symptoms to treatment with one of two mood stabilizers, lithium \[Li\] at baseline. Lithium is one of these two mood stabilizers. The person may or may not stay solely on lithium throughout the study.

Drug: Lithium

Divalproex

ACTIVE COMPARATOR

This open methods advancement study will randomize BD patients with clinically significant symptoms to treatment with one of two mood stabilizers, divalproex (DV)at baseline. Divalproex is one of these two mood stabilizers. The person may or may not stay solely on divalproex throughout the study.

Drug: Divalproex

Lithium plus Quetiapine

ACTIVE COMPARATOR

Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + quetiapine \[QT\].

Drug: Lithium; Drug: Quetiapine

Lithium plus Lamotrigine

ACTIVE COMPARATOR

Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + lamotrigine (LM).

Drug: Lithium; Drug: Lamotrigine

Divalproex plus Quetiapine

ACTIVE COMPARATOR

Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + quetiapine \[QT\].

Drug: Divalproex; Drug: Quetiapine

Divalproex plus Lamotrigine

ACTIVE COMPARATOR

Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + lamotrigine (LM).

Drug: Divalproex; Drug: Lamotrigine

Interventions

Lithium DRUG

Therapeutic dosage as indicated by participants condition with blood levels. LI will be dosed to attain Li of ≥0.5mEq/L (milliequivalents per liter).

Also known as: Lithium Carbonate

Lithium; Lithium plus Lamotrigine; Lithium plus Quetiapine

Divalproex DRUG

DV will be dosed to attain DV levels of ≥45mg/L.

Also known as: Depakote, Depakote ER

Divalproex; Divalproex plus Lamotrigine; Divalproex plus Quetiapine

Lamotrigine DRUG

LM will be incrementally dosed up to 400 mg/day, or, in combination with DV, 200 mg/day. Dosage may be reduced for adverse effects to one half of the target dose.

Also known as: Lamictal

Divalproex plus Lamotrigine; Lithium plus Lamotrigine

Quetiapine DRUG

QT will be started at 50 mg/day and titrated up to 300 mg as tolerated. QT will be discontinued if not tolerated at 100mg/day and the patient will be treated according to guidelines.

Also known as: Seroquel

Divalproex plus Quetiapine; Lithium plus Quetiapine

Eligibility Criteria

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

You may qualify if:

• DSM-IV TR (Diagnostic and Statistical Manual Edition IV Text Revision) diagnosis BD I or II as assessed by MINI PLUS (Mini International Neuropsychiatric Interview PLUS)
• Male or female ≥ 18 years old
• Currently symptomatic with a CGI-BP-S ≥3 for mania/hypomania \&/or depression for ≥ 2 weeks
• One of the following indicators of recent active illness: a depressive or manic or hypomanic or mixed episode in the past 12 months
• If female of child bearing age must use effective birth control.

You may not qualify if:

• Unwilling or unable to comply with study requirements
• Renal impairment (serum creatinine \> 1.5 mg/dL)
• If maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1
• Patients who have had intolerable side effects to QTP, Li, Div, or LTG
• Patients whose clinical status requires inpatient care
• Drug/alcohol dependence within the past 30 days
• Pregnancy as determined by serum pregnancy test or breastfeeding
• History of poor response to Li at a serum Li of ≥ 0.5 mEq/L (milliequivalents per Liter) or Div at a serum level of ≥ 45 mg/dL for at least 2 weeks.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78229-3900, United States

Location

Related Publications (1)

• Hashimoto Y, Kotake K, Watanabe N, Fujiwara T, Sakamoto S. Lamotrigine in the maintenance treatment of bipolar disorder. Cochrane Database Syst Rev. 2021 Sep 15;9(9):CD013575. doi: 10.1002/14651858.CD013575.pub2.

  PMID: 34523118 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Lithium; Lithium Carbonate; Valproic Acid; Lamotrigine; Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Charles Bowden, MD
• Organization: UT Health San Antonio

bowdenc@uthscsa.edu

2105675393

Study Officials

• Charles L. Bowden, M.D.

  University of Texas

  PRINCIPAL INVESTIGATOR

• Joseph R Calabrese, M.D.

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: May 1, 2012
• Study Start: June 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: August 19, 2020
• Results First Posted: August 14, 2020

Record last verified: 2020-08

Locations

US (2)