A Safe Ketamine-Based Therapy for Treatment Resistant Depression
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
研究概览
简要总结
Treatment resistant depression (TRD) is a major public health problem. Current therapeutic options for this patient population remain limited. With all available treatments, only a sub-set of those patients who achieve an antidepressant response are likely to achieve treatment-induced remission. The need for antidepressant medication that can provide both rapid and long lasting relief of TRD symptoms is widely recognized. There is new evidence that drugs that block NMDA glutamate receptors (NMDA antagonists) are promising candidates for meeting this need. Existing studies in TRD have used only a low-dose, brief infusion of ketamine that would not be expected to re-sensitize the NMDA receptor; in agreement with this theory, these prior studies have found only temporary improvements of depression. Our key hypothesis is that a higher-dose, longer-term ketamine infusion, such as that used in chronic pain studies, would provide a more robust and lasting improvement from depression.
Accordingly, we will test whether a 100-hour ketamine infusion would be more effective than the standard 40-minute ketamine infusion currently used in other TRD studies. We will randomize subjects to one of 2 arms: (1) 100-hour (+/- 4 hours) ketamine infusion plus clonidine for the entire infusion (2) 40-minute ketamine infusion (plus clonidine) following a 100+/- hour saline infusion. All subjects will receive clonidine, an alpha-2 agonist, to minimize side effects of ketamine (namely, brief/mild psychotic and cognitive symptoms).
详细描述
This experiment is a pilot study involving up to 20 healthy males or females between the ages of 18-65 to test whether a 100-hour ketamine infusion plus clonidine would be more effective, with longer lasting results, then the standard 40-minute ketamine infusion (plus clonidine). Each of the 2 arms, will be evaluated using a between subject, double-blind, randomized design.
- a. Controlled up to 100-hour IV ketamine infusion b. clonidine safener PO prior to infusion
- a. Controlled 40-minute IV ketamine infusion b. clonidine safener PO prior to infusion c. up to 100-hour(+/-)IV placebo (saline) infusion
- a. Controlled up to 100-hour IV ketamine infusion b. clonidine safener PO prior to infusion
- a.Controlled up to 100-hour IV ketamine infusion b. clonidine safener PO prior to infusion
In both conditions, participants will be admitted to the Washington University School of Medicine Clinical Research Unit at Barnes-Jewish Hospital for approximately 108-hours (Monday morning-Friday evening). Pulse, blood pressure, pulse-oximetry, and an electrocardiogram strip will be routinely monitored. Serial labs and clinical/safety ratings will be done pre-, during, and post-infusion, with the last assessments being used to assure that subjects have returned to their "baseline" prior to discharge from the research unit. Participants will continue to see their primary psychiatrist throughout the study.
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, Outcomes Assessor)
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
- 否
入选标准
- 未提供
排除标准
- •confirmed bipolar disorder, schizophrenia, or schizoaffective disorder;
- •current or recent substance abuse/dependence (or any lifetime recreational ketamine or PCP use);
- •any severe Axis II personality disorder or schizophrenia spectrum disorder that, in the PI's judgment, could confound diagnosis or adherence to treatment;
- •the presence of any abnormal laboratory findings or serious medical disorder or condition that may, in the judgment of the PI, confound the assessment of relevant biologic measures or diagnoses including: clinically significant organ system dysfunction; significant and uncontrolled endocrine disease, including diabetes mellitus; hypothyroidism; cardiovascular disease; coagulopathy; significant anemia; significant acute infection; glaucoma; dehydration; epilepsy; any diagnosed cardiac condition causing documented hemodynamic compromise or dysfunction of the SA or AV node; any diagnosed respiratory condition causing documented or clinically recognized hypoxia (e.g., chronic obstructive or restrictive pulmonary disease); after evaluation, anyone determined to have a potentially compromised airway that could be difficult to intubate; fever; BMI less than 14.5; or any medical condition known to interfere with cognitive performance; medication-related exclusions include memantine, or any medication that could be considered contraindicated ketamine;
- •current treatment with any medication contraindicated with ketamine or clonidine;
- •lifetime illegal use of PCP or ketamine; no clinical use of ketamine for past 3 months
- •meets DSM-IV criteria for Mental Retardation;
- •currently hospitalized;
- •acutely suicidal or homicidal (i.e., in imminent danger with plan, urges and intent to harm oneself or others) including any prior serious attempts (e.g., those requiring hospitalization) at the PI's discretion;
- •is pregnant or breast-feeding; unwilling to use birth control if female of child bearing potential
- •unable to provide informed consent.
研究组 & 干预措施
ketamine 100-hour infusion
100-hour infusion of ketamine plus a safener (clonidine)
干预措施: Ketamine (Drug)
ketamine 100-hour infusion
100-hour infusion of ketamine plus a safener (clonidine)
干预措施: Clonidine (Drug)
ketamine 40-minute infusion
40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine)
干预措施: Ketamine (Drug)
ketamine 40-minute infusion
40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine)
干预措施: Clonidine (Drug)
ketamine 40-minute infusion
40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine)
干预措施: placebo (Drug)
结局指标
主要结局
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
时间窗: 8 weeks
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item scale that measures the severity of depression, with a higher score indicating a higher level of depression. The range of scores is 0 to 60.
Clinical Global Impression (CGI) Global Improvement Score.
时间窗: 8 weeks
The Clinical Global Improvement is a 7-point scale where the anchors range from 1 (very much improved) to 7 (very much worse).
次要结局
未报告次要终点