Feasibility Trial of Pregnenolone for Posttraumatic Stress Disorder and Alcohol Use Disorder

NCT04464148 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: STU 2020-0171
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Pregnenolone is a neurosteroid and an over-the-counter supplement that has shown promise in clinical studies of stress-related disorders, such as anxiety, depression and posttraumatic stress disorder (PTSD). Epidemiological studies suggest that patients with PTSD are at higher risk of developing addiction, including alcohol use disorder (AUD).The following hypothesis will be tested in this trial: pregnenolone is associated with a reduction in both PTSD symptoms and the number of standard drinks per week in outpatients with PTSD and AUD.

Conditions

Post Traumatic Stress Disorder; Alcohol Use Disorder

Keywords

Pregnenolone; PTSD; Alcohol

Outcome Measures

Primary Outcomes (5)

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

  CAPS-5 is a 30-item questionnaire, corresponding to the DSM-5 diagnosis for PTSD. CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms. Similarly, CAPS-5 symptom cluster severity scores are calculated by summing the individual item severity scores for symptoms corresponding to a given DSM-5 cluster: Criterion B (items 1-5); Criterion C (items 6-7); Criterion D (items 8-14); and, Criterion E (items 15-20). A symptom cluster score may also be calculated for dissociation by summing items 19 and 20. The higher scores are associated with greater PTSD severity.

  Baseline to 8 weeks

• Standard alcoholic drinks per week

  The Timeline Followback will be used to assess the change in the number of standard alcoholic drinks per week. The TLFB will be administered by an interviewer and involves asking participants to retrospectively estimate their alcohol use 28 days prior to the first appointment and between each visit. The reported drinks are then converted to standard drinks based on the drink's alcohol by volume (ABV). The higher number is associated with more standard drinks and worse outcome.

  Baseline to 8 weeks

• Timeline Followback (TLFB) heavy drinking days

  The Timeline Followback will be used to assess the change in the number of standard alcoholic drinks per week. The TLFB will be administered by an interviewer and involves asking participants to retrospectively estimate their alcohol use 28 days prior to the first appointment and between each visit. The reported drinks are then converted to heavy drinking days based on the drink's alcohol by volume (ABV) and participant's sex (male/female) - 5 drinks per day for males and 4 for females. Each day during which 4-5 drinks are consumed is counted as a heavy drinking day within a given assessment period. The higher number is associated with more heavy drinking days and worse outcome.

  Baseline to 8 weeks

• Systematic Assessment for Treatment Emergent Events (SAFTEE)

  SAFTEE is a side effect self-report assessment scale that consists of 56 potential side effects. Participants rate how bothersome each side effect is on a scale of "none" (0), "mild" (1), "moderate" (2), "severe" (3). The higher total score (all items summed together) indicates a higher level of side effect burden.

  Baseline to 8 weeks

• Patient-rated PTSD Checklist for DSM-5 (PCL-5).

  The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The self-report rating scale is 0-4 for each symptom, reflecting a change from 1-5 in the DSM-IV version. Rating scale descriptors correspond to "Not at all" (0), "A little bit" (1), "Moderately" (2), "Quite a bit" (3), and "Extremely" (4).A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items. The higher score is associated with poorer outcome.

  Baseline to 8 weeks

Study Arms (1)

Pregnenolone 250 BID > Pregnenolone 400 BID

EXPERIMENTAL

For week 0-5 participants will receive pregnenolone 250 mg twice a day (total 500 mg/day). For weeks 6-8 participants will receive 400 mg twice a day (800 mg/day), if the drug is well tolerated.

Drug: Pregnenolone 250 mg; Drug: Pregnenolone 400 mg

Interventions

Pregnenolone 250 mg DRUG

Pregnenolone 250 mg capsule BID (500 mg QD total)

Pregnenolone 250 BID > Pregnenolone 400 BID

Pregnenolone 400 mg DRUG

Pregnenolone 400 mg capsule BID (800 mg QD total)

Pregnenolone 250 BID > Pregnenolone 400 BID

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatient adults (males and females) 18-70 years of age
• Meet criteria for current PTSD based on SCID-CV for DSM 5.
• Meet criteria for current AUD based on SCID-CV for DSM 5.
• Alcohol use of 14 standard drinks per week for men and 7 for women based on TLFB in the last week.
• Able to read and speak in English.
• If taking psychotropic medications, taking a stable dose for the past 2 weeks and during the study treatment.

You may not qualify if:

• Vulnerable populations (e.g., pregnancy/nursing, severe cognitive impairment, incarcerated).
• Current DSM-5 diagnosis of bipolar disorder, schizophrenia or other psychotic disorders based on SCID-CV.
• High risk for suicide (active SI with plan/intent or \> 3 lifetime attempts in lifetime or any in the past 3 months).
• Coronary artery disease, atrial fibrillation, stroke, deep vein thrombosis, pulmonary embolism or blood clotting disorder, uncontrolled hypertension, cirrhosis or any severe, life threatening or unstable, medical condition as determined by clinician assessment.
• Clinically significant laboratory or physical examination findings.
• AST or ALT \> 3 times the upper limit of normal.
• Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar score of ≥ 10.
• Current (last 14 days) treatment with naltrexone, acamprosate, disulfiram, topiramate.
• Intensive outpatient treatment (defined as ≥ 3 visits each week) for substance abuse (AA, NA meetings, or less intensive counseling at baseline will be allowed) or intensive psychosocial treatment for PTSD.
• Hormone-sensitive conditions (i.e. breast cancer; uterine/ovarian cancer, endometriosis, uterine fibroids).
• Use of oral contraceptives or hormone replacement therapy.
• History of allergic reaction or side effects with prior pregnenolone use.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Alcoholism

Interventions

Pregnenolone

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• E. Sherwood Brown, MD, PhD, MBA

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 3, 2020
• First Posted: July 9, 2020
• Study Start: December 1, 2021
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: August 23, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share