Comparison of Ketamine Versus Saline During Sedation in Patients With Major Depressive Disorder: a Double-blind Trial
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Protocol-concordant experiential report
研究概览
简要总结
This open-label, randomized crossover study in healthy adults tests two propofol protocols to produce distinct experiential states. One induces brief loss of responsiveness with spontaneous emergence, intended to elicit dream reports; the other maintains light sedation without loss of responsiveness, intended to elicit non-dream experiences while participants remain responsive. The main goals are to (a) measure the protocol-concordant experiential report rate (how often each method produces its intended experience), (b) explore EEG correlates of these experiences in the two states, and (c) describe their phenomenology (what they are like). We will also examine short-term changes in well-being and sleep related to these experiences. Participants complete four sessions (two of each method) with EEG and routine monitoring, immediate post-session interviews, and brief questionnaires and daily sleep/dream logs before and after anesthesia sessions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
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
- 是
入选标准
- •Male or female, 18 to 70 years of age, inclusive, at screen.
- •Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
- •In sufficiently good health to proceed with a low risk elective procedure, characterized using the American Society of Anesthesiologists (ASA) physical status classification system as Class 1 or
- •If female, a status of non-childbearing potential or use of an acceptable form of birth control
- •Body mass index between 17-35 kg/m2.
排除标准
- •Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
- •Female that is pregnant or breastfeeding.
- •Female with a positive pregnancy test at screening or baseline.
- •Current diagnosis of a Substance Use Disorder (SUD; Abuse or Dependence, as defined by DSM-V) rated "moderate" or "severe", or Alcohol Use Disorder rated "moderate" or "severe". The following categories of SUD will NOT be excluded: nicotine dependence; alcohol or substance use disorder rated "mild"; alcohol or substance use disorder of any severity in remission, either early (3-12 months) or sustained (>12 months) time frames.
- •Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, Specific Phobia, or Bipolar II Disorder
- •History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms
- •History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, within five years of screening.
- •In the judgment of the investigator, the subject is at significant risk for suicidal behavior during the course of his/her participation in the study.
- •A neurological disorder including:
- •Has dementia, delirium, amnestic, or any other cognitive disorder.
- •Lifetime history of surgical procedures involving the brain or meninges,
- •encephalitis, meningitis, degenerative central nervous system disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation
- •any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system (CNS),
- •history of significant head trauma within the past two years.
- •A cardiovascular disorder including:
- •uncontrolled hypertension
- •Congestive heart failure NYHA Criteria >Stage 2
- •Atrial fibrillation or resting heart rate <50 or >105 beats per minute at screening or randomization
- •Any conduction abnormalities including AV nodal block of any type or intraventricular conduction delay.
- •QTcF (Fridericia-corrected) >= 450 msec at screening or randomization
- •any cardiovascular disorder that would merit categorization of patient as ASA Class 3 or higher
- •A pulmonary/respiratory disorder including:
- •diagnosed Obstructive Sleep Apnea or STOPBANG score of 3 or higher
- •History of difficult airway in surgical setting
- •any pulmonary / respiratory disorder that would merit categorization of patient as ASA Class 3 or higher
- •Clinically significant liver disease, determined by LFTs within the past 6 months.
- •Clinically significant kidney disease determined by creatinine / GFR within the past 6 months.
- •Symptomatic gastroesophageal reflux disease, hiatal hernia, or other gastrointestinal disorder placing patient at risk for aspiration or that would merit categorization of patient as ASA Class 3 or higher
- •Any endocrine disorder including:
- •uncontrolled diabetes, type 1 or 2
- •History of hypothyroidism and has been on a stable dosage of thyroid replacement medication for less than six months prior to screening. (Subjects on a stable dosage of thyroid replacement medication for at least six months or more prior to screening are eligible for enrollment.)
- •History of hyperthyroidism which was treated (medically or surgically) less than six months prior to screening.
- •Other endocrine disorder that would merit categorization of patient as ASA Class 3 or higher
- •Patients taking any of the following daily medications:
- •opioids including buprenorphine and methadone
- •naltrexone or other opioid antagonist
- •Any other clinically significant abnormal laboratory result at the time of the screening exam.
- •Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation or confound interpretation of study results, including any condition that would merit categorization of patient as ASA Class 3 or higher.
- •Participation in any clinical trial with an investigational drug or device that conflicts with this trial, within the past month or concurrent to study participation.
研究组 & 干预措施
No-LOR Light Sedation Protocol
Participants receive propofol titrated stepwise to light sedation without LOR, maintaining responsiveness. This protocol is designed to elicit non-dream experiential reports while responsive (e.g., simple imagery, sounds, thoughts, bodily sensations, hypnagogic-like experiences).
干预措施: Propofol - Light Sedation Protocol (Drug)
Emergence-from-LOR Protocol
Participants receive propofol titrated to loss of responsiveness (LOR) followed by maintenance and spontaneous emergence. This protocol is designed to elicit dream reports upon emergence (i.e., reports of subjective experiences occurring during the unresponsiveness period)
干预措施: Propofol - Emergence-from-LOR Protocol (Drug)
结局指标
主要结局
Protocol-concordant experiential report
时间窗: Assessed within 5 minutes of return of responsiveness (LOR protocol) or within 5 minutes of session end (light-sedation protocol).
Presence vs absence of an experiential report elicited via a structured interview (modified Brice). "Protocol-concordant" is defined as: LOR protocol-success = any dream report upon emergence; Light-sedation (no-LOR) protocol-success = any experiential report that is not a dream (e.g., imagery, sounds, thoughts, bodily sensations, hypnagogic-like experiences) while the participant remained behaviorally responsive.
次要结局
- Change in dream outcomes(Baseline (2-week pre-session) to follow-up (2-week post-session).)
- Change in well-being: psychological (eudaimonic) well-being(Baseline (2-weeks pre-anesthesia) to follow-up (2-weeks post-anesthesia))
- EEG correlates of protocol-concordant experiential outcome(Matched-duration EEG windows during the 30-minute maintenance period: pre-emergence window prior to return of responsiveness in the LOR protocol, and a time-matched window during maintenance in the no-LOR protocol.)
- Phenomenology of anesthesia experiences (analysis of narrative reports)(Interview immediately post-session)
- Phenomenology of anesthesia experiences (self-ratings)(Interview immediately post-session)
- Change in well-being: peace of mind(Baseline (2-weeks pre-anesthesia) to follow-up (2-weeks post-anesthesia))
- Dream vs dream-like experiences (within-anesthesia) - phenomenological differences(Interview immediately post-session)
- Home dreams vs anesthesia dreams - phenomenological differences(Home dream logs (2 weeks pre-session and 2 weeks post-session) vs anesthesia interview (immediate post-session).)
- Change in well-being: life satisfaction(Baseline (2-weeks pre-anesthesia) to follow-up (2-weeks post-anesthesia))
- Safety outcomes(From pre-anesthesia baseline to post-anesthesia discharge)
- Changes in daily mood(Baseline (2-week pre-session average) to follow-up (2-week post-session average))
- Change in sleep quality(Baseline (2-week pre-session) to follow-up (2-week post-session))
- Change in well-being: harmony in life(Baseline (2-weeks pre-anesthesia) to follow-up (2-weeks post-anesthesia))
- Change in alexithymia score(Baseline (2-weeks pre-anesthesia) to follow-up (2-weeks post-anesthesia))
- Change in emotion regulation(Baseline (2-weeks pre-anesthesia) to follow-up (2-weeks post-anesthesia))
- Change in symptoms of depression(Baseline (2-weeks pre-anesthesia) to follow-up (2-weeks post-anesthesia))
- Change in symptoms of anxiety(Baseline (2-weeks pre-anesthesia) to follow-up (2-weeks post-anesthesia))
- Change in perceived loneliness(Baseline (2-weeks pre-anesthesia) to follow-up (2-weeks post-anesthesia))
研究者
Boris D. Heifets
Associate Professor of Anesthesiology, Perioperative and Pain Medicine
Stanford University