Sequential Multiple Assignment Randomized Trial for Bipolar Depression
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 2,726
- 试验地点
- 18
- 主要终点
- The Remission from Depression Questionnaire
研究概览
简要总结
This is a sequential multiple assignment randomized trial for adults (ages > 18) with a bipolar disorder type 1 and type 2 diagnosis currently experiencing a depressive episode. It is a randomized pragmatic trial that will compare four commonly prescribed treatments for bipolar depression, which includes three FDA-approved medications (Cariprazine, Quetiapine and Lurasidone) and one antipsychotic/antidepressant combination (Aripiprazole/Escitalopram).
详细描述
This is a comparative effectiveness study to address the critical questions of how best to treat people with bipolar disorder who have a major depressive episode: how to get them well, provide second-line treatment when they don't initially get well, and keep them well after they get well. This is a multisite Sequential Multiple Assignment Randomized Trial (SMART) comparative effectiveness design. Investigators will recruit 2726 participants who have BD I or II with a current major depressive episode lasting at least 2 weeks. In Stage 1, investigators will compare four treatment arms, including three FDA approved monotherapies and the most widely used, but understudied, treatment for BD major depressive episode (i.e., a non-FDA approved combination of an antipsychotic and antidepressant). In Stage 2, participants who do not remit will be re-randomized to treatments not used in Stage 1. Investigators will follow all participants for a total of 52 weeks. This study will be conducted in two phases, a feasibility phase and a full study phase. In the feasibility phase, investigators will recruit at 8 of the 19 study sites based on readiness and interest, to ensure the efficacy of the study design before launching the full study phase.
Feasibility Aim 1: To ensure that 8 of the 19 selected sites can recruit, randomize, and retain participants. During the feasibility phase, the selected sites will recruit 133 participants, administer baseline assessments, randomize the participants (at baseline and again at 6-weeks for non-remitters), and conduct follow-up assessments at the end of Stage 1 (6-weeks) and the end of Stage 2 (12-weeks) and end of study (52 weeks or end of feasibility phase, whichever is sooner) and all other scheduled visits.
Feasibility Aim 2: To refine and finalize all study standard operating procedures for the full-scale study. After Aim 1 is complete, any changes in standard operating procedures will be made as needed to be implemented in the full study phase.
Full Scale Study Full-Scale Study Aim 1: To compare the effectiveness, tolerability, and safety of the four treatments for BD major depressive episodes.
Hypothesis 1a: There will be significant differences across the Stage 1 treatments in the proportion of remitters at week 6 (primary endpoint, effectiveness) and in the average adverse event burden and suicidal ideation/behavior at week 6 (secondary endpoints, tolerability and safety).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between 18 years to 75 years
- •Meets criteria for DSM-V Bipolar I or II disorder with a history of manic or hypomanic episodes and current major depressive episode lasting at least 2 weeks
- •Can be managed as an outpatient and participate in the study
- •Willing to be randomized; able to perform study assessments
- •Women of childbearing potential must agree to use adequate contraception (e.g. oral contraceptives, intrauterine device, barrier methods, or total abstinence; Depo Provera is acceptable if it is started 3 months prior to enrollment), and inform staff of their plans to conceive.
排除标准
- •Meets current criteria for a manic episode, rapid cycling within the past year (history of 4 or more mood episodes per year)
- •History of schizophrenia or other nonaffective psychosis
- •Current substance use disorder that will interfere with participation in the study
- •Currently taking the study medications or a history of serious adverse events to any of the study medications, to the extent that as determined by site PI, another trial would not be clinically indicated
- •A history of non-response for depressive episodes, to any of the study medications, when given at adequate doses for at least 6 weeks
- •Current acute suicidal risk that requires inpatient treatment
- •Pregnancy or breastfeeding
研究组 & 干预措施
Aripiprazole /Escitalopram combination
干预措施: Aripiprazole/Escitalopram combination (Drug)
Lurasidone
干预措施: Lurasidone (Drug)
Quetiapine
干预措施: Quetiapine (Drug)
Cariprazine
干预措施: Cariprazine (Drug)
结局指标
主要结局
The Remission from Depression Questionnaire
时间窗: Investigators will administer this measure every 2 weeks for the first 12 weeks (weeks:0,2,4,6,8,10,12), and then at each study visit during the follow up phase until they are discharged from the study (weeks:20,28,36,44,52 ).
RDQ is a 41 items self report questionnaire used to assess the seven domains found in extensive previous research to be important to patients: depressive symptoms, anxiety, coping ability, positive mental health, functioning, life satisfaction and a general sense of well-being. Using a score of 27 as the cutoff, the RDQ scale has a sensitivity of 83.7% and specificity of 77.9% in predicting self-reported remission status. The RDQ has excellent internal consistency reliability (Cronbach's alpha of 0.97 for the total scale and above 0.80 for each of the 7 subscales with test-retest reliability of the total scale = 0.85 and \> 0.60 for each subscale). The primary outcome will be remission as defined by a RDQ score \< 27. This test will be administered in all assessment visits. The RDQ scale ranges from 0-27 per domain, with higher scores indicating greater remission rates.
次要结局
- Frequency and Intensity of Side Effects Ratings - Intensity(Investigators will administer this measure every 2 weeks for the first 12 weeks (weeks:0,2,4,6,8,10,12), and then at each study visit during the follow up phase until they are discharged from the study (weeks:20,28,36,44,52 ).)
- Frequency and Intensity of Side Effects Ratings - Frequency(Investigators will administer this measure every 2 weeks for the first 12 weeks (weeks:0,2,4,6,8,10,12), and then at each study visit during the follow up phase until they are discharged from the study (weeks:20,28,36,44,52 ).)
- Safety: Concise Health Risk Tracking Scale(Investigators will administer this measure every 2 weeks for the first 12 weeks (weeks:0,2,4,6,8,10,12), and then at each study visit during the follow up phase until they are discharged from the study (weeks:20,28,36,44,52 ).)
- Frequency and Intensity of Side Effects Ratings - Burden(Investigators will administer this measure every 2 weeks for the first 12 weeks (weeks:0,2,4,6,8,10,12), and then at each study visit during the follow up phase until they are discharged from the study (weeks:20,28,36,44,52 ).)
研究者
Andrew A. Nierenberg, MD
Director, Dauten Family Center for Bipolar Treatment Innovation
Massachusetts General Hospital