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

Phase 2

Not yet recruiting

• Conditions: Post-traumatic Stress Disorder; PTSD
• Interventions: Procedure: Propofol anesthesia

• Registration Number: NCT06577636
• Lead Sponsor: Stanford University

Brief Summary

The goal of this study is to test the efficacy of anesthesia-induced dreaming for PTSD in a double-blind, randomized controlled trial in a non-surgical setting (Phase II). We predict that inducing and sustaining a dream state prior to emergence from anesthesia will result in reduced symptoms of PTSD. Half of the participants will be randomly allocated to a Dream Group, while the other half will be in the No-Dream group.

Detailed Description

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. We have preliminary evidence that dreaming during anesthesia may reduce symptoms of PTSD (Chow et al., 2022; Hack, Sikka et al., 2024). 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 double-blind, randomized controlled trial in a non-surgical setting (Phase II). We predict that inducing and sustaining a dream state prior to emergence from anesthesia will result in reduced symptoms of PTSD.

STUDY DESIGN

Randomization: Double-blind, sham-controlled RCT

Sample Size: 42 (21 in Dream group, 21 in No-Dream group)

Variables: Outcome variables include: (1) Clinician-Administered PTSD Scale (CAPS-5; Weathers et al., 2013); (2) PTSD Checklist for DSM-5 (PCL-5; Weathers et al., 2013)

STUDY PROCEDURES AND MEASURES

This research study is expected to take approximately 3 months to complete (per participant). During this time, we will ask participants to make 1 screening visit via zoom and 1 in-person screening visit at Stanford Hospital. We also ask participants to complete daily assessments of sleep quality and dream experiences 2 weeks before and 2 weeks after the anesthesia 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 targeted to reach a Dream or No-Dream state. Immediately upon emerging from anesthesia, participants will be interviewed using the modified Brice questionnaire and their responses audio recorded.

Study Timeline

• Status Verified: 2024-08
• Study First Submitted: 2024-08-27
• Study First Submitted QC: 2024-08-27
• Last Update Submitted: 2024-08-27
• Study First Posted: 2024-08-29
• Last Update Posted: 2024-08-29
• Study Start: 2024-12
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 42

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, inclusive, at screen.

2. 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.

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. Concurrent psychotherapy will be allowed if the type (e.g., supportive, cognitive behavioral, insight-oriented, et al) and frequency (e.g., weekly or monthly) of the therapy has been stable for at least 4 weeks prior to screening and if the type and frequency of the therapy is expected to remain stable during the course of the subject's participation in the study.

6. Concurrent antidepressant therapy (e.g. SSRI or SNRI) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study.

7. 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.

8. If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:

   1. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her last menses at least one year prior to screening); or
   2. Childbearing potential, and meets the following criteria:

   i. Childbearing potential, including women using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or is sexually abstinent.

   ii. Negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test at randomization prior to receiving study treatment.

   iii. Willing and able to continuously use one of the following methods of birth control during the course of the study, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly: implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence. The form of birth control will be documented at screening and baseline.

9. Body mass index between 17-32 kg/m2.

Exclusion Criteria

A potential participant will NOT be eligible for participation if any of the following criteria are met:

1. Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.

2. Female that is pregnant or breastfeeding.

3. Female with a positive pregnancy test at screening or baseline.

4. Total CAPS-5 score ≤20 at either the screening or day of infusion visits.

5. 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.

6. 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)

7. History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes.

8. History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, within five years of screening.

9. 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.

10. 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.

11. A neurological disorder including:

    1. Has dementia, delirium, amnestic, or any other cognitive disorder
    2. Lifetime history of surgical procedures involving the brain or meninges
    3. Encephalitis, meningitis, degenerative central nervous system disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation
    4. Any other disease/procedure/accident/intervention of the central nervous system (CNS) that in the view of the investigator poses a risk for participation in this study

12. A cardiovascular disorder including:

13. Uncontrolled hypertension

14. Congestive heart failure NYHA Criteria >Stage 2

15. Atrial fibrillation or resting heart rate <50 or >105 beats per minute at screening or randomization

16. Any clinically significant conduction abnormalities (eg 2nd degree AV nodal block or left bundle branch block)

17. QTcF (Fridericia-corrected) >= 450 msec at screening or randomization

18. Any cardiovascular disorder that would merit categorization of patient as ASA Class III or higher 11. A pulmonary/respiratory disorder including:

a. Diagnosed Obstructive Sleep Apnea or STOPBANG score of 3 or higher b. History of difficult airway in surgical setting c. Any pulmonary / respiratory disorder that would merit categorization of patient as ASA Class III or higher 12. Clinically significant liver disease, determined by LFTs within the past 6 months.

13. Clinically significant kidney disease determined by GFR (<40 mL/min, Cockcroft-Gault Equation) within the past 6 months.

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. Any endocrine disorder including:

15. Uncontrolled diabetes, type 1 or 2

16. 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.)

17. History of hyperthyroidism which was treated (medically or surgically) less than six months prior to screening.

18. Other endocrine disorder that would merit categorization of patient as ASA Class 3 or higher 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. Has 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 III or higher.

    18. 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).

    19. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dream Group	Propofol anesthesia	Dream Group (n=21) will be subjected to an anesthetic protocol resulting in dream experiences during anesthesia.
No-Dream Group	Propofol anesthesia	No-Dream Group (n=21) will be subjected to an anesthetic protocol resulting in no dream experiences during anesthesia.

Primary Outcome Measures

Name	Time	Method
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)	1 month post-intervention	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 group" over "No-Dream group" will be demonstrated by a statistically significant greater decrease in the CAPS-5 when comparing pre-anesthesia scores to post-anesthesia scores.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Response	1 month post-intervention	Clinical response is defined as a reduction of ≥15 points (or ≥30% - 50%) in the score of CAPS-5 in the Dream Group, comparing baseline pre-anesthesia scores to post-anesthesia scores.
Number of Participants With Remission	1 month post-intervention	Remission is defined as obtaining a score of ≤20 points on the CAPS-5 in the Dream Group post-intervention.
PTSD Checklist for DSM-5 (PCL-5)	1 month post-intervention	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.

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States