Specialized Pro-resolving Lipid Mediators and Treatment Resistant Depression
概览
- 阶段
- 2 期
- 干预措施
- Omega 3
- 疾病 / 适应症
- Treatment Resistant Depression
- 发起方
- Massachusetts General Hospital
- 入组人数
- 80
- 试验地点
- 3
- 主要终点
- 18-HEPE (18-hydroxy eicosapentaeoic acid) Change
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
The goal of this clinical trial is to determine the impact of omega-3 fatty acids on the production of anti-inflammatory effects and clinical improvement in people with depression who have not responded well to standard antidepressant treatment. The main questions it seeks to answer are:
- Do omega-3 fatty acids added to ineffective antidepressant treatment increase production of compounds that reduce inflammation?
- Is the increase in these anti-inflammatory compounds associated with a stronger antidepressant effect?
Participants taking antidepressants that have not worked completely will be assigned at random for a 12-week period to one of the following:
- an omega-3 preparation
- an inactive placebo
During the course of the study, blood tests will be obtained for compounds associated with inflammation, and questionnaires to measure clinical improvement in depressive symptoms will be administered.
详细描述
This R33 application builds directly on a previous collaborative R01 (NCT00517036) and UG3 (NCT02553915) grants. The investigators will carry out a 12-week, randomized placebo-controlled, double-masked, augmentation trial of 4 g/day eicosapentaenoic acid (EPA)-enriched omega-3 treatment in adults with major depressive disorder (MDD), an inadequate response to antidepressants (treatment-resistant depression \[TRD\]), body mass index (BMI) \>25 kg/m2 and ≤ 40 kg/m2, and inflammation (high sensitivity C reactive protein \[hs-CRP\] ≥ 3 mg/L and ≤ 10 mg/L). It is hypothesized that 4 g/day of EPA-enriched omega-3 will: 1) Significantly increase plasma 18-hydroxy eicosapentaeoic acid \[18-HEPE\] concentrations compared to placebo (primary biological endpoint); 2) produce significantly greater increases in plasma 18-HEPE concentration since baseline for sustained MADRS responders (those with at least 50% reduction since baseline in MADRS scores at both treatment week 8 and week 12) than for (a) unsustained/non-responders to EPA-enriched n-3 as well as (b) placebo-supplemented sustained responders (secondary biological endpoint).
研究者
David Mischoulon, MD, PhD
Director, Depression Clinical and Research Program
Massachusetts General Hospital
入排标准
入选标准
- •Age: 18 to 65 years
- •Patients with treatment-resistant MDD who have not responded to at least 2 and no more than 5 antidepressant trials of at least 8 weeks duration during the current episode and have been on a current stable antidepressant regiment for at least 4 weeks. The diagnosis of MDD will be confirmed using the MINI and the historical failure to respond to antidepressant therapy will be documented using the Antidepressant Treatment Response Questionnaire (ATRQ), with failure to respond defined as less than 50% improvement by subject history.
- •hs-CRP ≥ 3 mg/L and ≤ 10 mg/L
- •BMI \>25 kg/m2 and ≤ 40 kg/m2
- •17-item Hamilton Depression Rating Scale (HAM-D) score ≥15, and \<25% decrease in score between screen and baseline
排除标准
- •Diagnostic Exclusions:
- •Meeting lifetime DSM-5 criteria for: a neurocognitive disorder, psychotic disorder, bipolar disorder, obsessive compulsive disorder, bulimia nervosa, or anorexia nervosa in the 3 months prior to the screening; any substance use disorder (except for nicotine or caffeine use disorder).
- •Patients who, in the investigator's judgment, pose a current, serious suicidal or homicidal risk
- •Presence of a serious or unstable medical illness, including insulin-dependent diabetes mellitus or bleeding disorder which, in the investigator's opinion, could compromise response to treatment, participant safety, or interpretation of study results.
- •Currently breastfeeding, pregnant women, or women of childbearing ability, who do NOT agree to use a study approved method of birth control (described in the MOP) for the duration of the study.
- •Currently or within 90 days of screen participating in another clinical trial (excluding large natural cohort trials such as 'All of Us').
- •Treatment and Concomitant Medication Exclusions:
- •Failure to respond during the course of the current major depressive episode to \>5 adequate antidepressant trials
- •Current use of antipsychotic medications or lithium
- •Having received ketamine therapy within 90 days of the screening visit
研究组 & 干预措施
Omega-3
Omega-3 fatty acid (ProEPA Xtra) capsules containing a total of 4 g/day of eicosapentaenoic acid (EPA), administered for 12 weeks.
干预措施: Omega 3
Placebo
Placebo capsules containing soybean oil (about 54% omega-6 and 6% omega-3, but no EPA or docosahexaenoic acid (DHA)), and matched to the ProEPA Xtra capsules in terms of appearance, odor, and taste.
干预措施: Placebo
结局指标
主要结局
18-HEPE (18-hydroxy eicosapentaeoic acid) Change
时间窗: 12 weeks
Evaluate change in plasma 18-HEPE (18-hydroxy eicosapentaeoic acid) levels associated with 12 weeks of 4 g/day EPA-enriched n-3 treatment vs placebo.
次要结局
- 18-HEPE (18-hydroxy eicosapentaeoic acid) Change in Treatment Responders(12 weeks)