Utility of Brexanolone to Target Stress-induced Alcohol Use Among Men and Women With Posttraumatic Stress Disorder

Sponsor

Yale University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05223829

Collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH), Sage Therapeutics (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

For this protocol, the investigators plan to collect pilot data to: 1. establish the feasibility and safety of administering brexanolone to individuals with concurrent Posttraumatic Stress Disorder (PTSD) and Alcohol Use Disorder (AUD).

Condition or Disease	Intervention/Treatment	Phase
PTSD Alcohol Use Disorder	Drug: Brexanolone	Phase 1

Detailed Description

This project is a Phase 1 (open-label, single arm, proof of concept) laboratory design. It will investigate the feasibility and safety of administering brexanolone to men and women with PTSD/AUD.

Eligibility screening consists of an intake session and a physical exam. Subjects meeting eligibility criteria will be administered brexanolone as a continuous IV infusion over 20 hours. Participants will be monitored during infusion by medical personnel. Forty-eight hours following drug administration, participants will then complete a laboratory session.

During the laboratory session, personalized imagery (stress) will precede a 2 hour alcohol self-administration period. Subjects will then complete a follow-up period, including assessments of alcohol use, PTSD symptoms, and side effects weekly for the next 30 days.

Primary outcome measures include treatment-emergent adverse events following administration of brexanolone for 30-days, as well as the percentage of milliliters consumed during ad-libitum drinking in the laboratory session. Additionally, at each visit the participants will complete a timeline follow-back assessment for a 30-day period (or the number of days in between intake, drug, and laboratory sessions) to explore a sustained reduction in in-vivo alcohol use.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This project is a Phase 1 (open-label, single arm, proof of concept) laboratory design. It will investigate the feasibility and safety of administering brexanolone to men and women and collect preliminary data to understand brexanolone's efficacy to reduce stress-induced drinking in individuals with PTSD/AUD.This project is a Phase 1 (open-label, single arm, proof of concept) laboratory design. It will investigate the feasibility and safety of administering brexanolone to men and women and collect preliminary data to understand brexanolone's efficacy to reduce stress-induced drinking in individuals with PTSD/AUD.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Utility of Brexanolone to Target Stress-induced Alcohol Use Among Men and Women With Posttraumatic Stress Disorder

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brexanaolone In this single-arm study, participants will be administered brexanolone as a continuous IV infusion over 20 hours (titrated up to 90mcg/kg/hour).	Drug: Brexanolone Brexanolone will be administered as a continuous IV infusion over 20 hours under medical observation Other Names: Zulresso

Arm

Intervention/Treatment

Experimental: Brexanaolone

In this single-arm study, participants will be administered brexanolone as a continuous IV infusion over 20 hours (titrated up to 90mcg/kg/hour).

Drug: Brexanolone

Brexanolone will be administered as a continuous IV infusion over 20 hours under medical observation

Other Names:

Zulresso

Outcome Measures

Primary Outcome Measures

Treatment-emergent adverse events [30 days following administration of brexanolone]
Treatment-emergent adverse events will be assessed following administration of brexanolone.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 21-55 years old
Meet DSM-5 diagnostic criteria for AUD within the past 6 months, as well as the following drinking criteria:
Men: drink greater than 14 drinks per week and exceed five drinks per day at least once per week within the past 30 days
Women: drink greater than 7 drinks per week and exceed four drinks per day at least once per week within the past 30 days
Meet DSM-5 diagnostic criteria for PTSD in the past 6 months

Exclusion Criteria:

Actively seeking treatment for AUD
Likely to experience clinically significant alcohol withdrawal during the study procedures (e.g., history of alcohol-related perceptual distortions/hallucinations, seizures, or Clinical Institute Withdrawal Assessment Scale score > 8 at intake)
Current (i.e., past month) active suicidal ideation and/or homicidal ideation
Meets DSM-5 diagnostic criteria for schizophrenia, bipolar disorder, and/or other severe mental illnesses.
Meets criteria for current (past 6 months) substance use disorders (other than tobacco use disorder).
Tests positive for illicit substances during urine toxicology screens (except cannabis) at intake session
Is actively engaged in psychotherapy to treat PTSD
Any significant current medical conditions (neurological, cardiovascular [including hypertension or hypotension: sitting BP >160/100 or <90/60mmHg at baseline screening], endocrine, thyroid, renal, liver), seizures, delirium or hallucinations, or other unstable medical conditions including HIV
Past 30 day use of psychoactive drugs including anxiolytics and antidepressants.
Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or her partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD)
Specific exclusions for the administration of brexanolone not already specified include: Individuals with end stage renal disease, treatment with any opioids or other CNS depressants, such as benzodiazepines.
Subjects likely to exhibit clinically significant alcohol withdrawal during the study. Specifically, we will exclude subjects who a) have a history of perceptual distortions, seizures, delirium, or hallucinations upon withdrawal or b) have a score of > 8 on the Clinical Institute Withdrawal Assessment scale at intake appointments.
Participation within the past 8 weeks in other studies that involve additive blood sampling and/or interventional measures that would be considered excessive in combination with the current application