<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04464148</url>
  </required_header>
  <id_info>
    <org_study_id>STU 2020-0171</org_study_id>
    <nct_id>NCT04464148</nct_id>
  </id_info>
  <brief_title>Feasibility Trial of Pregnenolone for Posttraumatic Stress Disorder and Alcohol Use Disorder</brief_title>
  <official_title>Feasibility Trial of Pregnenolone for Posttraumatic Stress Disorder and Alcohol Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pregnenolone is a neurosteroid and an over-the-counter supplement that has shown promise in&#xD;
      clinical studies of stress-related disorders, such as anxiety, depression and posttraumatic&#xD;
      stress disorder (PTSD). Epidemiological studies suggest that patients with PTSD are at higher&#xD;
      risk of developing addiction, including alcohol use disorder (AUD).The following hypothesis&#xD;
      will be tested in this trial: pregnenolone is associated with a reduction in both PTSD&#xD;
      symptoms and the number of standard drinks per week in outpatients with PTSD and AUD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Investigators will conduct an 8-week, non-randomized, open label trial of pregnenolone in 20&#xD;
      persons with PTSD and AUD. The study will serve as a pilot study to determine feasibility and&#xD;
      collect pilot data for NIH R01 proposals. All participants will be titrated to 800 mg/day of&#xD;
      pregnenolone over the course of 4 weeks and maintain this dose for the remainder of the&#xD;
      study. The study will consist of a screening visit to determine eligibility (Baseline I) and&#xD;
      a Baseline II visit where participants will receive study medication, and follow-up visits at&#xD;
      Weeks 1, 2, 3, 4, 6, and 8. Participants will complete a variety of assessments at each study&#xD;
      visit, including clinician-rated and self-report measures of PTSD, alcohol use, depressive&#xD;
      symptoms, cognitive performance, and side effects. Blood work will be done to ensure&#xD;
      participant health and safety prior to randomization into the study, as well as to assess&#xD;
      pregnenolone blood levels. All participants will meet with a study clinician at each visit to&#xD;
      monitor safety and assess any adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Feasibility study was not initiated.&#xD;
  </why_stopped>
  <start_date type="Anticipated">December 2021</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Standard alcoholic drinks per week</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Timeline Followback (TLFB) heavy drinking days</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Systematic Assessment for Treatment Emergent Events (SAFTEE)</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <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 &quot;none&quot; (0), &quot;mild&quot; (1), &quot;moderate&quot; (2), &quot;severe&quot; (3). The higher total score (all items summed together) indicates a higher level of side effect burden.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient-rated PTSD Checklist for DSM-5 (PCL-5).</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <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 &quot;Not at all&quot; (0), &quot;A little bit&quot; (1), &quot;Moderately&quot; (2), &quot;Quite a bit&quot; (3), and &quot;Extremely&quot; (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.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Post Traumatic Stress Disorder</condition>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Pregnenolone 250 BID &gt; Pregnenolone 400 BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pregnenolone 250 mg</intervention_name>
    <description>Pregnenolone 250 mg capsule BID (500 mg QD total)</description>
    <arm_group_label>Pregnenolone 250 BID &gt; Pregnenolone 400 BID</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pregnenolone 400 mg</intervention_name>
    <description>Pregnenolone 400 mg capsule BID (800 mg QD total)</description>
    <arm_group_label>Pregnenolone 250 BID &gt; Pregnenolone 400 BID</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Outpatient adults (males and females) 18-70 years of age&#xD;
&#xD;
          -  Meet criteria for current PTSD based on SCID-CV for DSM 5.&#xD;
&#xD;
          -  Meet criteria for current AUD based on SCID-CV for DSM 5.&#xD;
&#xD;
          -  Alcohol use of 14 standard drinks per week for men and 7 for women based on TLFB in&#xD;
             the last week.&#xD;
&#xD;
          -  Able to read and speak in English.&#xD;
&#xD;
          -  If taking psychotropic medications, taking a stable dose for the past 2 weeks and&#xD;
             during the study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Vulnerable populations (e.g., pregnancy/nursing, severe cognitive impairment,&#xD;
             incarcerated).&#xD;
&#xD;
          -  Current DSM-5 diagnosis of bipolar disorder, schizophrenia or other psychotic&#xD;
             disorders based on SCID-CV.&#xD;
&#xD;
          -  High risk for suicide (active SI with plan/intent or &gt; 3 lifetime attempts in lifetime&#xD;
             or any in the past 3 months).&#xD;
&#xD;
          -  Coronary artery disease, atrial fibrillation, stroke, deep vein thrombosis, pulmonary&#xD;
             embolism or blood clotting disorder, uncontrolled hypertension, cirrhosis or any&#xD;
             severe, life threatening or unstable, medical condition as determined by clinician&#xD;
             assessment.&#xD;
&#xD;
          -  Clinically significant laboratory or physical examination findings.&#xD;
&#xD;
          -  AST or ALT &gt; 3 times the upper limit of normal.&#xD;
&#xD;
          -  Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar&#xD;
             score of ≥ 10.&#xD;
&#xD;
          -  Current (last 14 days) treatment with naltrexone, acamprosate, disulfiram, topiramate.&#xD;
&#xD;
          -  Intensive outpatient treatment (defined as ≥ 3 visits each week) for substance abuse&#xD;
             (AA, NA meetings, or less intensive counseling at baseline will be allowed) or&#xD;
             intensive psychosocial treatment for PTSD.&#xD;
&#xD;
          -  Hormone-sensitive conditions (i.e. breast cancer; uterine/ovarian cancer,&#xD;
             endometriosis, uterine fibroids).&#xD;
&#xD;
          -  Use of oral contraceptives or hormone replacement therapy.&#xD;
&#xD;
          -  History of allergic reaction or side effects with prior pregnenolone use.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>E. Sherwood Brown, MD, PhD, MBA</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Southwestern Medical Center</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>August 19, 2021</last_update_submitted>
  <last_update_submitted_qc>August 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Sherwood Brown, MD, PhD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Pregnenolone</keyword>
  <keyword>PTSD</keyword>
  <keyword>Alcohol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Alcohol Drinking</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04464148
org study id: STU 2020-0171
nct id: NCT04464148
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
time frame: Baseline to 8 weeks
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.
measure: Standard alcoholic drinks per week
time frame: Baseline to 8 weeks
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.
measure: Timeline Followback (TLFB) heavy drinking days
time frame: Baseline to 8 weeks
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.
measure: Systematic Assessment for Treatment Emergent Events (SAFTEE)
time frame: Baseline to 8 weeks
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.
measure: Patient-rated PTSD Checklist for DSM-5 (PCL-5).
time frame: Baseline to 8 weeks
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.
arm group label: Pregnenolone 250 BID > Pregnenolone 400 BID
arm group type: Experimental
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: Pregnenolone 250 mg
description: Pregnenolone 250 mg capsule BID (500 mg QD total)
arm group label: Pregnenolone 250 BID > Pregnenolone 400 BID
intervention type: Drug
intervention name: Pregnenolone 400 mg
description: Pregnenolone 400 mg capsule BID (800 mg QD total)
arm group label: Pregnenolone 250 BID > Pregnenolone 400 BID
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: E. Sherwood Brown, MD, PhD, MBA
role: Principal Investigator
affiliation: UT Southwestern Medical Center
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Sherwood Brown, MD, PhD
investigator title: Professor
mesh term: Alcoholism
mesh term: Stress Disorders, Traumatic
mesh term: Alcohol Drinking
mesh term: Stress Disorders, Post-Traumatic
sharing ipd: No