Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 17
- 主要终点
- Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline
研究概览
简要总结
This is a study that will test a predictive biomarker algorithm based on results from a previous study. The goal of this study is to integrate clinical, imaging, EEG, and molecular data across 8 sites to predict treatment outcome for patients experiencing a major depressive episode (MDE).
详细描述
This is a multi-site, randomized study with two treatment phases: a double-blind primary treatment phase of 8 weeks, and an open-label secondary extension phase of 4 weeks. This study aims to test a predictive biomarker algorithm to select medication treatment for patients with major depressive disorder (MDD) based on results from the recently completed Canadian Biomarker Integration Network in Depression (CAN-BIND)-1 study. This will be accomplished through collection of clinical, neurophysiological, and molecular measures from both MDD patients and healthy controls. This is not a study to evaluate efficacy of medications; medications in this study have been approved by Health Canada and are widely used for the treatment of MDD.
In this study, individuals diagnosed with MDD in a current major depressive episode (MDE) will be randomly assigned to one of the two treatment groups: Personalized Assignment group or Random Assignment group. Patients in the Random Assignment group will randomly receive open-label escitalopram with the addition of either blinded placebo or brexpiprazole for 8 weeks. Patients in the Personalized Assignment group will receive open-label escitalopram with the addition of either placebo or blinded brexpiprazole for 8 weeks depending on what the predictive biomarker algorithm suggests.
At Week 8, participants will be assessed for treatment response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale score). All patients who initially received both open-label escitalopram and blinded brexpiprazole (regardless of treatment group) will continue to receive these medications for another 4 weeks but the brexpiprazole will no longer be blinded. For those patients who initially received open-label escitalopram and blinded placebo (regardless of treatment group), nonresponders will receive open-label escitalopram and open-label brexpiprazole for another 4 weeks and responders will receive open-label escitalopram only for another 4 weeks.
Over the 12 weeks, participants will attend 7 study visits where they will complete clinical assessments (clinician administered and self-report) and cognitive tests; provide blood, urine, and stool samples; undergo neuroimaging procedures (MRI and EEG); and provide speech samples. At the end of the study, modeling methods will be used to integrate data from these measures to determine the features that best predict treatment outcome.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion Criteria:
- •Outpatients 18 to 65 years of age.
- •Meet DSM-5 criteria for MDE in MDD as determined by SCID-
- •Free of psychotropic medications for at least 5 half-lives (e.g. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1 (exceptions: stable use of hypnotics; stable use of stimulants for attention-deficit/hyperactive disorder).
- •MADRS score ≥
- •Fluency in English, sufficient to complete the interviews and self-report questionnaires.
排除标准
- •Any diagnosis, other than MDD, that is considered the primary diagnosis.
- •Bipolar I or Bipolar-II diagnosis.
- •Presence of a significant Axis II diagnosis (borderline, antisocial).
- •High suicidal risk, defined by clinician judgment.
- •Substance dependence/abuse in the past 6 months.
- •Presence of significant neurological disorders, head trauma, or other unstable medical conditions.
- •Pregnant or breastfeeding.
- •Failure of 4 or more adequate pharmacologic interventions (as determined by the Antidepressant Treatment History Form).
- •Started psychological treatment within the past 3 months with the intent of continuing treatment.
- •Patients who have previously failed escitalopram or showed intolerance to escitalopram or brexpiprazole, and patients at risk for hypomanic switch (i.e. with a history of antidepressant induced hypomania).
- •Healthy Comparison (HC) Participants
- •Inclusion Criteria:
- •18 to 65 years of age.
- •No history of psychiatric disorders (as determined by SCID-5) or significant physical conditions (e.g. arthritis, fibromyalgia).
- •Fluency in English, sufficient to complete the interviews and self-report questionnaires.
研究组 & 干预措施
Random Allocation; Placebo
Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.
干预措施: Escitalopram (Drug)
Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole
Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted as non-responders to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.
干预措施: Escitalopram (Drug)
Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole
Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted as non-responders to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.
干预措施: Brexpiprazole (Drug)
Random Allocation; Escitalopram + Brexpiprazole
Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.
干预措施: Escitalopram (Drug)
Allocation by Predictive Biomarker Algorithm; Placebo
Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted to respond to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.
干预措施: Escitalopram (Drug)
Random Allocation; Escitalopram + Brexpiprazole
Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.
干预措施: Brexpiprazole (Drug)
结局指标
主要结局
Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline
时间窗: Baseline to Week 8
Measured as clinical response, defined as a decrease in Montgomery Asberg Depression Rating Scale (MADRS) score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit (i.e., lower MADRS scores = better outcome)
次要结局
- Remission at Week 8(Week 8)
- Clinical response(Baseline to Week 8)
- Time to clinical response(Baseline to Week 8)
研究者
Rudolf Uher
Staff Psychiatrist, Independent Investigator, Professor
Nova Scotia Health Authority