Effect of Ketamine on Laboratory-induced Stress in Healthy Subjects: A Proof-of-Concept Translational Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change in The Profile of Mood States - Bipolar Version (POMS - Bi) Composed-Anxious Subscale
研究概览
简要总结
The objective of this study is to examine the effect of a single IV dose of ketamine (0.5 mg/kg) on laboratory-induced stress in healthy participants.
详细描述
Stress exposure is one of the greatest risk factors for psychiatric illnesses like major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Stress resilience is the ability to experience stress without developing psychopathology. Enhancing stress resilience in at-risk populations could potentially protect against the development of stress-induced psychiatric disorders. Despite this, no resilience-enhancing pharmaceuticals have been identified yet. Pre-clinical studies showed that the administration of the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine one week before an acute stress prevents the developing of depressive-like behavior in animals. In this project the study team proposes a pilot study to test if this stress prophylactic effect of ketamine applies also to humans. Ketamine will be compared to an active placebo control condition, the anesthetic midazolam, in a sample of healthy volunteers. The specific aims of this project are to test the effect of ketamine administered 1-week prior a laboratory-induced stress (1) on the positive and negative affect as measured with the Profile of Mood States (POMS) - Bipolar and (2) on the hypothalamic-pituitary-adrenal axis (HPA axis), adrenaline-noradrenaline axis (ANS axis), and self-reports of anxiety. The study team expects that subjects treated with ketamine, compared to midazolam, will experience reduced symptoms of negative affect and anxiety and a blunted hormonal response to an acute stress.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Midazolam has similar acute anesthetic effects compared to ketamine. This makes midazolam an appropriate substance to gauge whether ketamine can affect stress response thereby acting as an active control.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females aged 18-45 years;
- •Does not meet for any current or past psychiatric diagnoses as defined by DSM-V criteria;
- •Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.
排除标准
- •Any current or lifetime psychiatric disorder as determined by the Structured Clinical Interview for DSM-V Axis Disorders (SCID-5);
- •Concomitant use of any medication with central nervous system activity, including treatment with antidepressants (classified as SSRIs, SNRIs, Atypical Antidepressants, TCAs);
- •Any unstable medical illnesses including hepatic, renal impairment, gastroenterologic (including gastro-esophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
- •Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) at screening or immediately prior to treatment with ketamine/midazolam;
- •Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG; clinically significant is defined by an abnormality that suggests a disease and/or organ toxicity that is new or has worsened from screening, or if the abnormality is of a degree that requires additional active management (e.g., further diagnostic investigation).
- •Patients who have a positive urine toxicology test for illicit substances at screening and on the treatment day.
- •Previous recreational use of PCP or ketamine.
- •Subjects who have received ketamine in the past.
研究组 & 干预措施
Ketamine group
One 0.5mg/kg intravenous dose of ketamine
干预措施: Ketamine (Drug)
Midazolam group
One 0.045mg/kg intravenous dose of midazolam
干预措施: Midazolam (Drug)
结局指标
主要结局
Change in The Profile of Mood States - Bipolar Version (POMS - Bi) Composed-Anxious Subscale
时间窗: baseline and 1 week after infusion
Change from pre- to post-TSST in The Profile of Mood States - Bipolar Version (POMS - Bi) scale measures moods and feelings primarily in clinical rather than nonclinical settings. The POMS-Bi consists of 72 adjectives that form six bipolar sub-scale scores (Composed - Anxious, Clear - Confused, Confident - Unsure, Agreeable - Hostile, Energetic - Tired, Elated - Depressed). Each of the 12 adjectives within each subscale is rated on a 4-point Likert scale with anchors of 0 = "much unlike this," 1 = "slightly unlike this," 2 = "slightly like this," and 3 = "much like this." The Composed-Anxious Subscale score is the sum of positive minus the sum of negative responses plus a constant of 18. The subscale score range is from 0 to 36. Higher score indicates higher functioning. Each subscale is separate and there is no overall score.
次要结局
- Change in Heart Rate(baseline and 1 week after infusion)
- Change in Salivary Cortisol(baseline and 1 week after infusion)
- Change in Systolic Blood Pressure(baseline and 1 week after infusion)
- Change in Beck Anxiety Inventory (BAI)(baseline and 1 week after infusion)
- Change in Diastolic Blood Pressure(baseline and 1 week after infusion)
- Change in Salivary Alpha-amylase Level(baseline and 1 week after infusion)
- Change in Positive and Negative Affect Scale (PANAS)(baseline and 1 week after infusion)
- Change in Visual Analog Scale: Stressed (VAS-Stressed)(baseline and 1 week after infusion)
研究者
James Murrough
Associate Professor
Icahn School of Medicine at Mount Sinai