Overview

This trial is active, not recruiting.

Conditions bipolar i disorder, bipolar ii disorder
Treatments lithium/lithium carbonate, divalproex, lamotrigine, quetiapine
Phase phase 4
Sponsor The University of Texas Health Science Center at San Antonio
Collaborator National Institute of Mental Health (NIMH)
Start date June 2011
End date December 2016
Trial size 200 participants
Trial identifier NCT01588457, 1P30MH086045-01A2, HSC20110361H

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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.
lithium/lithium carbonate Lithium Carbonate
Therapeutic dosage as indicated by participants condition with blood levels. LI will be dosed to attain LI of ≥0.5mEq/L.
(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.
divalproex Depakote
DV will be dosed to attain DV levels of ≥45mg/L.
(Active Comparator)
Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + quetiapine [QT].
lithium/lithium carbonate Lithium Carbonate
Therapeutic dosage as indicated by participants condition with blood levels. LI will be dosed to attain LI of ≥0.5mEq/L.
quetiapine Seroquel
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.
(Active Comparator)
Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + lamotrigine (LM).
lithium/lithium carbonate Lithium Carbonate
Therapeutic dosage as indicated by participants condition with blood levels. LI will be dosed to attain LI of ≥0.5mEq/L.
lamotrigine Lamictal
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.
(Active Comparator)
Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + quetiapine [QT].
divalproex Depakote
DV will be dosed to attain DV levels of ≥45mg/L.
quetiapine Seroquel
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.
(Active Comparator)
Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + lamotrigine (LM).
divalproex Depakote
DV will be dosed to attain DV levels of ≥45mg/L.
lamotrigine Lamictal
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.

Primary Outcomes

Measure
Bipolar Inventory of Symptoms Scale (BISS)
time frame: Baseline and 26 weeks

Secondary Outcomes

Measure
Global Assessment of Functioning Scale (GAF)
time frame: Baseline and 26 weeks

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - DSM-IV TR diagnosis BD I or II as assessed by MINI 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. Exclusion Criteria: - 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 QT, LI, DV, or LM - 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 or DV at a serum level of ≥ 45 mg/dL for at least 2 weeks.

Additional Information

Official title Sequential Multiple Assignment Randomized Treatment (SMART) for Bipolar Disorder
Principal investigator Charles L. Bowden, M.D.
Description This open methods advancement study will randomize BD patients with clinically significant symptoms to treatment with one of two mood stabilizers (MS), lithium [LI] or divalproex [DV]. Those who develop protocol defined depression will then be randomized to a MS alone, MS + quetiapine [QT] or MS + lamotrigine [LM]. A SMART strategy employs a rule for adding new treatments based on each patient's current illness state and response during the trial, mimicking the adaptive nature of treatment selection which occurs in clinical settings, but in a controlled way which allows application of causal inference. By using early indices of response to dynamically alter treatment decisions to improve outcome, SMART eliminates unmeasured confounders associated with treatment decisions that are not randomized, as occurs in data mining exercises and in other non-randomized decisions in studies which randomize one variable at baseline. This sequential adaptive design represents a methodological innovation in bipolar trial history which will have particular implications for effectiveness studies. Specific Aim A.1: Assess the feasibility of a SMART design in the conduct of an effectiveness study over 26 weeks in patients with BD. Aim A.2 Compare the effectiveness of LI to DV as a primary component of treatment for BD over 26 weeks. Aim A.3: Assess the effectiveness of MS + QT and MS + LM versus MS in subjects who develop depression. A4. Exploratory Aims: 1.Determine the effects of ethnicity, language facility, education and stress as moderators of treatment outcomes; 2. Explore the use of novel statistical methodologies to more informatively characterize illness trajectories in response to the interventions. In the aggregate these aims also will clarify whether the SMART confirms results provided by traditional, single point randomized controlled trials (RCTs).
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by The University of Texas Health Science Center at San Antonio.