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

Primary Purpose

Post Traumatic Stress Disorder, Alcohol Use Disorder

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Pregnenolone 250 mg
Pregnenolone 400 mg
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Post Traumatic Stress Disorder focused on measuring Pregnenolone, PTSD, Alcohol

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Pregnenolone 250 BID > Pregnenolone 400 BID

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    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.
    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.
    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.
    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.
    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.

    Secondary Outcome Measures

    Full Information

    First Posted
    July 3, 2020
    Last Updated
    August 19, 2021
    Sponsor
    University of Texas Southwestern Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04464148
    Brief Title
    Feasibility Trial of Pregnenolone for Posttraumatic Stress Disorder and Alcohol Use Disorder
    Official Title
    Feasibility Trial of Pregnenolone for Posttraumatic Stress Disorder and Alcohol Use Disorder
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2021
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Feasibility study was not initiated.
    Study Start Date
    December 2021 (Anticipated)
    Primary Completion Date
    December 2021 (Anticipated)
    Study Completion Date
    December 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Texas Southwestern Medical Center

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.
    Detailed Description
    Investigators will conduct an 8-week, non-randomized, open label trial of pregnenolone in 20 persons with PTSD and AUD. The study will serve as a pilot study to determine feasibility and collect pilot data for NIH R01 proposals. All participants will be titrated to 800 mg/day of pregnenolone over the course of 4 weeks and maintain this dose for the remainder of the study. The study will consist of a screening visit to determine eligibility (Baseline I) and a Baseline II visit where participants will receive study medication, and follow-up visits at Weeks 1, 2, 3, 4, 6, and 8. Participants will complete a variety of assessments at each study visit, including clinician-rated and self-report measures of PTSD, alcohol use, depressive symptoms, cognitive performance, and side effects. Blood work will be done to ensure participant health and safety prior to randomization into the study, as well as to assess pregnenolone blood levels. All participants will meet with a study clinician at each visit to monitor safety and assess any adverse events.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Post Traumatic Stress Disorder, Alcohol Use Disorder
    Keywords
    Pregnenolone, PTSD, Alcohol

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Pregnenolone 250 BID > Pregnenolone 400 BID
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Pregnenolone 250 mg
    Intervention Description
    Pregnenolone 250 mg capsule BID (500 mg QD total)
    Intervention Type
    Drug
    Intervention Name(s)
    Pregnenolone 400 mg
    Intervention Description
    Pregnenolone 400 mg capsule BID (800 mg QD total)
    Primary Outcome Measure Information:
    Title
    Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
    Description
    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.
    Time Frame
    Baseline to 8 weeks
    Title
    Standard alcoholic drinks per week
    Description
    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.
    Time Frame
    Baseline to 8 weeks
    Title
    Timeline Followback (TLFB) heavy drinking days
    Description
    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.
    Time Frame
    Baseline to 8 weeks
    Title
    Systematic Assessment for Treatment Emergent Events (SAFTEE)
    Description
    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.
    Time Frame
    Baseline to 8 weeks
    Title
    Patient-rated PTSD Checklist for DSM-5 (PCL-5).
    Description
    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.
    Time Frame
    Baseline to 8 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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. Exclusion Criteria: 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    E. Sherwood Brown, MD, PhD, MBA
    Organizational Affiliation
    UT Southwestern Medical Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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

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