Brexanolone to Target Concurrent PTSD and Stress Induced Alcohol Use in Veterans: A Dose Finding Study
NCT Number: NCT06580444
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Alcohol Use Disorder (AUD)|Post Traumatic Stress Disorder (PTSD)
Interventions: DRUG: Brexanolone
Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance
Collaborators: United States Department of Defense|Congressionally Directed Medical Research Programs|VA Connecticut Healthcare System|Yale University|Sage Therapeutics|RTI International
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: OTHER
Start Date: 2024-10-24
Completion Date: 2027-03-19

Summary:
The purpose of this research study is to find out how Zulresso®/brexanolone influences Posttraumatic Stress Disorder (PTSD) symptoms and alcohol use.

Primary Outcome Measures: Severity and numbers of treatment-emergent AEs, The number and proportion of individuals experiencing any adverse event, any SAE, and any related adverse event overall will be summarized using frequency tables. No formal statistical tests will be conducted, rather the safety will be evaluated from a risk/benefit perspective. Any p-values reported will be for descriptive purposes only., From onset of Brexanolone administration until 30-day follow up.|Change in Heart Rate from onset of Brexanolone administration until discharge from the drug administration session., The change in heart rate a physiological safety/stress measure are continuous and obtained multiple times after study drug administration which occurs on day 1. This measure will be analyzed using descriptive statistics and graphical summaries including time-specific summary statistics (e.g., box and whisker plots)., An average of 22 hours (From the start of Brexanolone administration on day 1 at 10 am until 7 am on day 2)|Change in Blood Pressure from onset of Brexanolone administration until discharge from the drug administration session., The change in blood pressure a physiological safety/stress measure are continuous and obtained multiple times after study drug administration which occurs on day 2. This measure will be analyzed using descriptive statistics and graphical summaries including time-specific summary statistics (e.g., box and whisker plots)., An average of 22 hours (From the start of Brexanolone administration on day 1 at 10 am until 7 am on day 2)|Change in Cortisol from onset of Brexanolone administration until discharge from the drug administration session., The change in Cortisol a physiological safety/stress measure are continuous and obtained multiple times after study drug administration which occurs on day 2. This measure will be analyzed using descriptive statistics and graphical summaries including time-specific summary statistics (e.g., box and whisker plots)., FAn average of 22 hours (From the start of Brexanolone administration on day 1 at 10 am until 7 am on day 2)|Change in percentage of milliliters of alcohol consumed during the 2-hour ad-libitum drinking paradigm between laboratory sessions (stress vs. neutral)., A set of dose-response models will be tested response using the Multiple Comparisons Procedure Modifications (MCP-Mod) methodology including change in percentage of milliliters consumed during the 2-hour ad-libitum drinking paradigm within laboratory sessions (stress and neutral) as dependent variable, the treatment as factor (90, 60, 30 and 0 mcg/kg/h), and baseline dependent value. These dose-response models with repeated measures will be used to test the effects of the regimens of 90, 60, and 30 mcg/kg/h doses of brexanolone on alcohol consumption in self-administration., During the 2-hour ad-libitum drinking paradigm between lab sessions (stress Vs Neutral)|Change in Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) score from intake until 30-day follow-up, Another set of dose-response models will test Multiple Comparisons Procedure Modifications (MCP-Mod) methodology for the 30-day follow-up in PCL-5 score as dependent variable, the treatment as factor (90, 60, 30 and 0 mcg/kg/h), and baseline dependent value. These dose-response models will be used to test the effects of the regimens of 90, 60, 30 and 0 mcg/kg/h doses of brexanolone on PTSD symptoms.

Scale PCL-5 is 0-4 with 0 being not at all and 4 being extreme; the higher score is worse outcome, From intake, day 0 through day 37 (30-day follow-up).|Change in Change in Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) score from intake until end of dosing., Another set of dose-response models will test Multiple Comparisons Procedure Modifications (MCP-Mod) methodology including change from intake to end of dosing in PCL-5 score as dependent variable, the treatment as factor (90, 60, 30 and 0 mcg/kg/h), and baseline dependent value. The same modeling will be repeated for the 30-day follow-up timepoint. These dose-response models will be used to test the effects of the regimens of 90, 60, 30 and 0 mcg/kg/h doses of brexanolone on PTSD symptoms.

Scale PCL-5 is 0-4 with 0 being not at all and 4 being extreme; the higher score is worse outcome, An average of 22 hours (From intake, day 0 through end of infusion on Day 2)