Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Number of Participants With 50% or Greater Improvement in MADRS Scores From Baseline
研究概览
简要总结
The investigators will compare 3 treatment groups (ketamine plus naltrexone vs. ketamine alone vs. placebo) for treating major depressive disorder (MDD) and alcohol use disorder (AUD) in an 8-week randomized, double-blind, placebo-controlled, between-subjects trial. First, prior to the double-blind trial, the investigators will conduct an open-label trial that will include 5 patients with comorbid MDD and AUD to test safety and efficacy of repeated ketamine treatment (0.5 mg/kg; once a week for 4 weeks; a total of 4 ketamine infusions) with a follow-up of 4 weeks. Second, after reviewing the safety and efficacy of repeated ketamine treatment from the open-label trial, the investigators will conduct an 8-week, randomized, double-blind, placebo-controlled trial that will include 60 patients with comorbid MDD and AUD to test safety and efficacy of repeated ketamine treatment (0.5 mg/kg; once a week for 4 weeks; a total of 4 ketamine infusions) plus naltrexone with a follow-up of 4 weeks. The 4-month follow-up session will also occur.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female veterans and civilians, 21-65 years old
- •Current major depressive disorder without psychotic features by DSM-5 (antidepressant regimens can be allowed and changed during the trial)
- •Montgomery-Asberg Depression Rating Scale (MADRS) 20 or higher
- •A minimum of 4 of 11 current alcohol use disorder symptoms by DSM-5
- •Heavy drinking at least 4 times in the past month ('heavy drinking' defined as 5 standard drinks per day for men and 4 standard drinks per day for women
- •Able to provide written informed consent
排除标准
- •Current substance use disorder by DSM-5 in the past 3 months (except alcohol, tobacco, or cannabis)
- •Current or past history of psychotic features or psychotic disorder
- •Current dementia
- •Current uncontrolled hypertension (systolic BP > 170 mm Hg or diastolic BP > 100 mm Hg)
- •Unstable medical condition or allergy to ketamine, midazolam, naltrexone, or lorazepam---clinically determined by a physician
- •Imminent suicidal or homicidal risk
- •Pregnant or nursing women, positive pregnancy test, or inadequate birth control methods in women of childbearing potential
- •Positive opioid or illicit drug screen test (except marijuana)
- •Opioid use within 10 days prior to study medication (injectable naltrexone) or risks for opioid use during the study
- •Liver enzymes that are three times higher than the upper limit of normal
- •Current use of benzodiazepine
- •Acute narrow-angle glaucoma
- •Severe sleep apnea---clinically determined by a physician
研究组 & 干预措施
Ketamine + Naltrexone
Subjects in this arm will receive (1) intravenous ketamine treatment once a week for 4 weeks (a total of 4 infusions) with a follow-up of 4 weeks and (2) intramuscular naltrexone once a month (a total of 2 injections).
干预措施: Ketamine + Naltrexone (Drug)
Ketamine + Placebo
Subjects in this arm will receive (1) intravenous ketamine treatment once a week for 4 weeks (a total of 4 infusions) with a follow-up of 4 weeks and (2) intramuscular placebo once a month (a total of 2 injections).
干预措施: Ketamine + Placebo (Drug)
Placebo (psychoactive placebo midazolam) + Placebo
Subjects in this arm will receive (1) intravenous placebo treatment (psychoactive placebo midazolam) once a week for 4 weeks (a total of 4 infusions) with a follow-up of 4 weeks and (2) intramuscular placebo once a month (a total of 2 injections).
干预措施: Placebo (psychoactive placebo midazolam) + Placebo (Drug)
结局指标
主要结局
Number of Participants With 50% or Greater Improvement in MADRS Scores From Baseline
时间窗: Day 21 (after 4th infusion, 240 minutes)
Our primary analysis (severity of depression) was to compare the proportions of subjects with clinical response in symptoms of major depressive disorder (response defined as a 50% or greater improvement from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores) at the end-of-treatment time point (Day 21, after 4th infusion, T+240 minutes).
Rate of Complete Abstinence From Alcohol
时间窗: Day 28
Alcohol consumption was measured using the Time Line Follow Back (TLFB) method. The rates of complete abstinence from alcohol across visits 3 (day 0) through visit 7 (day 28) were compared among the three study groups.
次要结局
未报告次要终点