The Additive Effect of Ketamine in Combination With ElectroConvulsive Stimulation (ECS) in Major Depressive Disorder (MDD): a Translational Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Mean change in depressive symptoms, as measured by MADRS scale
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled phase 3 clinical trial evaluating the additive effect of intravenous ketamine in combination with electroconvulsive therapy (ECT) in patients with treatment-resistant major depressive disorder (MDD). The study aims to determine whether ketamine enhances the antidepressant efficacy of ECT and reduces associated cognitive side effects. Thirty hospitalized patients diagnosed with treatment-resistant MDD will be randomized to receive either ketamine or placebo (saline) during ECT sessions 2, 4, and 6. Primary outcome is the change in depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4 weeks.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects ages 18-70,
- •diagnosed with MDD (according to SCID5-CV interview)
- •treatment resistant (defined as at least 2 different antidepressant agents used without success),
- •ability to give informed consent,
- •adequacy of the score for anesthesia.
排除标准
- •Chronic neurological diseases,
- •Intellectual disability
- •Contraindications to the electroconvulsive therapy (severe aortic valve stenosis, implantable cardiac defibrillators, uncontrolled hypertension, clinically significant respiratory, renal or hepatic disease, abdominal aortic aneurysm, endocrine disorders, neuromuscular diseases, space occupying brain lesions, stroke in the last 6 months),
- •Patients with Alcohol Use Disorder or Substance Use Disorder or Substance Abuse history in the past year,
- •Pregnancy and lactation
- •Cardiovascular conditions,
- •Psychiatric Disorders,
- •Hepatic impairment,
- •Participants with a known hypersensitivity to ketamine or any of its excipients will be excluded from the study,
- •Participants with any contraindications to the use of ketamine, such as a history of severe cardiovascular conditions (e.g., uncontrolled hypertension, significant arrhythmias), intracranial hypertension, or severe liver impairment, will also be excluded to prevent potential adverse events.
研究组 & 干预措施
Placebo
Patients receive standard ECT treatment combined with placebo (0.9% sodium chloride solution), administered intravenously after induction with Propofol, during ECT sessions 2, 4, and 6, mimicking the ketamine group's schedule.
Intervention:
- Drug: Saline solution (NaCl 0.9%)
- Timing: ECT sessions 2, 4, and 6
- Background: Serves as control to assess the specific contribution of ketamine to antidepressant efficacy and cognitive outcomes.
干预措施: Placebo (Drug)
Ketamine
Patients receive standard ECT treatment combined with intravenous ketamine at a subanesthetic dose of 0.5 mg/kg, administered after induction with Propofol. Ketamine is administered during ECT sessions 2, 4, and 6.
Intervention:
- Drug: Ketamine
- Dose: 0.5 mg/kg IV
- Timing: ECT sessions 2, 4, and 6
- Background: Investigating the additive antidepressant and potential cognitive-protective effects of ketamine in patients with treatment-resistant depression undergoing ECT.
干预措施: Ketamine Hydrochloride (Drug)
结局指标
主要结局
Mean change in depressive symptoms, as measured by MADRS scale
时间窗: From baseline (day 0) to day 28 (7 days after the last ECT session). A follow-up assessment at Week 12 (90 days) will be included
The primary efficacy endpoint will be assessed using the MADRS score (Montgomery-Åsberg Depression Rating Scale)
次要结局
- Change in Suicidal Ideation (Beck Scale for Suicide Ideation - BSSI)(Assessment will be performed at: baseline (day 0); Weekly during ECT treatment period (Weeks 1, 2, 3); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session))
- Change in Anxiety Symptoms (Hamilton Anxiety Rating Scale - HAM-A)(Assessment will be performed at: baseline (day 0); Weekly during ECT treatment period (Weeks 1, 2, 3); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session))
- Change in Cognitive Function (Brief Assessment of Cognition in Affective Disorders - BAC-A)(Assessment will be performed at: baseline (day 0); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session))
- Change in Dissociative and Psychotic Symptoms (Clinician-Administered Dissociative States Scale - CADSS; Brief Psychiatric Rating Scale - BPRS)(Assessment will be performed at: Baseline (Day 0, before first ECT session); Week 1 (After ECT session 2); Week 2 (After ECT session 4); Week 3 (After ECT session 6); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT)
- Change in Neurochemical Markers (Plasma Levels of Trp, 5-HT, 5-HIAA, Glutamate, Aspartate)(Assessment will be performed at: Baseline (Day 0, before first ECT session); Weekly during ECT treatment period (Weeks 1, 2, 3))
研究者
Giovanni Landoni
MD, Full Professor
Università Vita-Salute San Raffaele