RecruitingPhase 2NCT07079761

Facilitation of Extinction Retention and Reconsolidation Blockade by IV Allopregnanolone in PTSD.

Sponsor

Massachusetts General Hospital

Enrollment

96 participants

Start Date

Aug 4, 2025

Study Type

INTERVENTIONAL

Conditions

Post Traumatic Stress Disorder

Summary

Purpose: About 6.4% of the U.S. population suffers from posttraumatic stress disorder (PTSD). Trauma-focused psychotherapies are generally effective in PTSD, but responses vary greatly across individuals and PTSD subpopulations. Neurobiological factors impacted by life experiences, stress, and genetics can affect treatment responses. These factors can alter brain capacities needed to reprocess traumatic memories prevent them from triggering intensely distressing, disruptive, out-of-place responses. For example, during psychotherapy for PTSD, trauma memory activation engages two competing brain processes that affect recovery: "extinction" versus "reconsolidation" of trauma-related emotional, physiological, and behavioral responses. This study tests whether a single intravenous (IV) dose of allopregnanolone (Allo) compared to placebo (which is non-active): promotes consolidation of extinction learning (sub-study 1) or blocks reconsolidation of physiological responses triggered by aversive memories (sub-study 2). The study also tests whether Allo compared to placebo affects retention of non-aversive memories.

Eligibility

Min Age: 18 YearsMax Age: 55 Years

Plain Language Summary

Simplified for easier understanding

This study is testing whether an intravenous (IV) infusion of a naturally occurring hormone called allopregnanolone can help reduce the fear and distress associated with PTSD (post-traumatic stress disorder). The study focuses on whether this treatment can help the brain "unlearn" traumatic memories during therapy sessions. **You may be eligible if...** - You are between 18 and 55 years old and speak English - You have been diagnosed with chronic PTSD lasting more than 3 months - You are generally healthy and not taking certain prohibited medications - You are willing to abstain from alcohol and drugs for several weeks during the study - Women must have a natural menstrual cycle (no hormonal birth control, with exceptions for certain IUDs) **You may NOT be eligible if...** - You have a moderate or severe substance use disorder within the past 3 months - You have bipolar I disorder, schizophrenia, or active psychotic symptoms - You have had a suicide attempt in the past year - You have severe kidney disease, sleep apnea, or resting blood oxygen below 96% - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BEHAVIORALExperiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigm

Day 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Extinction training will occur followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on extinction retention as well as reinstatement of conditioned psychophysiological reactions will be assessed.

DRUGAllopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.

On Day 2 of Experiment 1, a 1.7 mcg/kg dose of IV Allo will be administered over 5 minutes at the completion of extinction training to raise resting plasma Allo plus pregnanolone (PA) levels by 1500 pg/ml. This will be followed by a 4-5-hour continuous infusion of IV Allo at 2.6 mcg/kg/hr to maintain resting plasma Allo levels at the target level.

BEHAVIORALExperiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigm

OTHERMatching IV Placebo

On Day 2 of Experiment 1, participants randomized to placebo will receive IV matching placebo over 5 minutes at the completion of extinction training followed by a continuous infusion of matching placebo over the next 4-5 hours. The matching IV placebo will be administered according to the same per kg dosing regimen as that for active drug.

BEHAVIORALExperiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigm

Day 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Brief exposure to the conditioned stimulus will be followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on reconsolidation blockade and reinstatement of conditioned psychophysiological reactions will be assessed.

On Day 2 of Experiment 2, a 28 mcg/kg dose of IV Allo will be infused over 30 minutes following brief reactivation of aversively conditioned psychophysiological reactions, after which IV fluid only (0.9% normal saline) will be administered over 4-5 hours.

BEHAVIORALExperiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigm

Day 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Brief exposure to the conditioned stimulus will be followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on reconsolidation blockade and reinstatement of conditioned psychophysiological reactions will be assessed.

OTHERMatching IV Placebo

On Day 2 of Experiment 2, matching IV placebo will be infused over 30 minutes following brief reactivation of aversively conditioned psychophysiological reactions, after which IV fluid only (0.9% normal saline) will be administered over the 4-5 hours. The matching IV placebo will be administered according to the same per kg dosing regimen as that for active drug.