Induction of Dreaming With EEG and Anesthesia for Post-traumatic Stress Disorder

Phase 2RecruitingNCT06577636

Stanford University42 enrolled

Overview

The goal of this study is to test whether anesthesia-induced dreaming can help alleviate symptoms of PTSD in an (1) open-label trial (Phase I) and (2) double-blind, randomized controlled trial (Phase II) in a non-surgical setting. The investigators predict that inducing and sustaining a dream state prior to emergence from anesthesia will result in reduced symptoms of PTSD. Participants will undergo EEG-guided propofol anesthesia during which they will be either (1) receiving deep sedation leading to loss of responsiveness, designed to elicit dream reports upon emergence (Dream Protocol), and/or (2) light sedation without loss of responsiveness, designed to elicit non-dream experiential reports while responsive (e.g., simple imagery, sounds, thoughts, bodily sensations, hypnagogic-like experiences) (Non-Dream Protocol). The investigators will then investigate whether the deep-sedation Dream Condition is associated with a larger reduction in PTSD symptoms than the light-sedation Non-Dream Condition.

GENERAL BACKGROUND Post-traumatic stress disorder (PTSD) affects millions of Americans, and it can make everyday life very challenging. PTSD is characterized by recurrent distressing memories and nightmares, flashbacks, hyperarousal, and avoidance of things that remind individuals of their traumatic event. Nightmares reflect impaired emotion regulation occurring during sleep. There is evidence that therapeutic applications of dreaming may help target nightmares and other PTSD symptoms because dreaming is involved in memory (re)processing and emotion regulation. There is preliminary evidence that dreaming during anesthesia may reduce symptoms of PTSD. However, larger studies are needed to systematically test this. AIM AND HYPOTHESES The aim of this study is to test the efficacy of anesthesia-induced dreaming for PTSD in a (1) open-label trial (Phase I) and (2) double-blind, randomized controlled trial (Phase II) in a non-surgical setting. The investigators predict that inducing and sustaining a dream state prior to emergence from anesthesia will result in reduced symptoms of PTSD. STUDY DESIGN Design: Phase I : Open-label study Phase II: Double-blind, sham-controlled RCT Sample Size: Phase I: N = 15 Phase II: N = 42 (21 in Dream Condition, 21 in Non-Dream Condition) Variables: Phase I and II: Outcome variables include: (1) Clinician-Administered PTSD Scale for DSM-5 (CAPS-5); (2) PTSD Checklist for DSM-5 (PCL-5) STUDY PROCEDURES AND MEASURES This research study is expected to take approximately 3 months to complete (per participant). During this time, participants will make 1 screening visit via zoom and 1 in-person screening visit at Stanford Hospital. Participants will also complete daily assessments of sleep quality and dream experiences 2 weeks before and 2 weeks after the anesthesia session. In Phase I, participants will also wear the Muse headband to measure sleep quantity and quality daily for 2 weeks before and 2 weeks after the intervention session. Participants will fill in pre-anesthesia and post-anesthesia questionnaires measuring mental health and well-being and, complete follow-up measures 1 week, 2 weeks, 1 month, and 3 months after the anesthesia session. During the anesthesia session, participants will undergo EEG-guided infusion of propofol. In Phase I, all participants will undergo at least two sessions: (1) an emergence-from-loss of responsiveness (LOR) protocol intended to elicit dream reports (Dream Condition); and (ii) light sedation without loss of responsiveness, designed to elicit non-dream experiential reports while responsive (e.g., simple imagery, sounds, thoughts, bodily sensations, hypnagogic-like experiences) (Non-Dream Condition). In Phase II, participants will be randomized into either the Dream or Non-Dream Group, undergoing either the protocol designed to elicit dream experiences or non-dream experiences during no-LOR, respectively. Immediately upon emerging from anesthesia, participants will be interviewed using the modified Brice questionnaire and their responses audio recorded.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: A subject will be eligible for inclusion when all of the following criteria are met: 1. Male or female, 18 to 70 years of age 2. Able to read, understand, and provide written, dated informed consent prior to screening. 3. Diagnosed with PTSD prior to screening, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition. The diagnosis of PTSD will be made by a trained study staff member and supported by the Structured Clinical Interview for DSM Disorders (SCID). 4. Meet the threshold of CAPS-5 score of \>20 during screening. 5. 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 I or II. 6. If female, a status of non-childbearing potential or use of an acceptable form of birth control 7. Body mass index between 17-35 kg/m2. Exclusion Criteria: A potential participant will NOT be eligible for participation if any of the following criteria are met: 1. Female who is pregnant or breastfeeding. 2. Total CAPS-5 score ≤20 at either the screening. 3. Current diagnosis of a Substance Use Disorder (SUD; Abuse or Dependence, as defined by DSM-V) rated "moderate" or "severe" per criteria of the SCID, or Alcohol Use Disorder rated "moderate" or "severe" per SCID criteria. 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. 4. 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 (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more) 5. History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes. 6. History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, within five years of screening. 7. Any Axis I or Axis II Disorder, which at screening is clinically predominant to their PTSD or has been predominant to their PTSD at any time within six months prior to screening. 8. 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. 9. A neurological disorder 10. A cardiovascular disorder 11. A pulmonary/respiratory disorder 12. Clinically significant liver disease 13. Clinically significant kidney disease 14. 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 III or higher 15. An endocrine disorder 16. Any other abnormal laboratory result at the time of the screening exam that in the view of the investigator poses a risk for participation in the study. 17. If, in the view of the participant's current primary mental health care provider this study poses a risk for participation (if a participant has a current mental health care provider). 18. 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.

Outcomes

Primary Outcomes

Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

The CAPS-5 is a structured interview that is considered the gold standard for assessing post-traumatic stress disorder (PTSD). The CAPS-5 is designed to assess the 20 symptoms of PTSD as defined by the DSM-5, as well as the impact of these symptoms on social and occupational functioning. The CAPS-5 includes 20 items corresponding to the DSM-5 criteria for PTSD. Each item is rated for both frequency and intensity, with a 5-point scale (0-4) for each dimension. The total score ranges from 0 to 80, with higher scores indicating more severe symptoms. A score of \>20 points indicates clinically significant PTSD symptoms. Superiority of "Dream Experiences Group" over "Non-Dream Experiences Group" will be demonstrated by a statistically significant greater decrease in the CAPS-5 when comparing pre-anesthesia scores to post-anesthesia scores.

Time frame: 1 month post-intervention

Secondary Outcomes

Number of Participants With Clinical Response

Clinical response is defined as a reduction of ≥15 points (or ≥30% - 50%) in the score of CAPS-5 in the Dream Experiences Group, comparing baseline pre-anesthesia scores to post-anesthesia scores.

Time frame: 1 month post-intervention

Number of Participants With Remission

Remission is defined as obtaining a score of ≤20 points on the CAPS-5 in the Dream Experiences Group post-intervention.

Time frame: 1 month post-intervention

PTSD Checklist for DSM-5 (PCL-5)

The PCL-5 is a self-report measure designed to assess the 20 symptoms of post-traumatic stress disorder (PTSD) as defined by the DSM-5. Includes 20 items that correspond directly to the DSM-5 criteria for PTSD. Each item is rated on a 5-point Likert scale from 0 (Not at all) to 4 (Extremely), indicating how much the symptom has bothered the individual in the past week/month. The total score can range from 0 to 80, with higher scores indicating more severe PTSD symptoms. A score of 31-33 or higher is considered indicative of symptomatic PTSD. Superiority of the Dream vs No-Dream group will be demonstrated by a reduction of ≥30% - 50% in the self-reported PTSD symptoms, as measured with the PCL-5, comparing baseline pre-anesthesia scores to post-anesthesia scores.

Time frame: 1 month post-intervention

Induction of Dreaming With EEG and Anesthesia for Post-traumatic Stress Disorder

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts