Clinical trial NCT01588457
Conditions: Bipolar I Disorder Bipolar II Disorder
Sponsor: The University of Texas Health Science Center at San Antonio
Start date: 2011-06-01; Completion date: 2016-12-01
Enrollment: 112 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Detailed 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 \[Div\]. Those who develop protocol defined depression will then be randomized to a MS alone, MS + quetiapine \[QTP\] or MS + lamotrigine \[LTG\]. 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 (bipolar disorder).

Aim A.2 Compare the effectiveness of Li to Div as a primary component of treatment for BD over 26 weeks.

Aim A.3: Assess the effectiveness of MS + QTP and MS + LTG 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).

Arms: arm 1: 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. arm 2: 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. arm 3: Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + quetiapine \[QT\]. arm 4: Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + lamotrigine (LM). arm 5: Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + quetiapine \[QT\]. arm 6: Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + lamotrigine (LM).
Interventions: intervention 1: Lithium intervention 2: Divalproex intervention 3: Lamotrigine intervention 4: Quetiapine
Intervention descriptions: intervention 1: Therapeutic dosage as indicated by participants condition with blood levels. LI will be dosed to attain Li of ≥0.5mEq/L (milliequivalents per liter). intervention 2: DV will be dosed to attain DV levels of ≥45mg/L. intervention 3: 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. intervention 4: 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.

Protocol documents: