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

Conditions

• Post Traumatic Stress Disorder

Eligibility Criteria

Sex

ALL

Age

18 Years - 55 Years

Healthy Volunteers

Accepted

Interventions

• Experiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigm — BEHAVIORAL
  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.
• Allopregnanolone (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. — DRUG
  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.
• Experiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigm — BEHAVIORAL
  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.
• Matching IV Placebo — OTHER
  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.
• Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigm — BEHAVIORAL
  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.
• Allopregnanolone (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. — DRUG
  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.
• Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigm — BEHAVIORAL
  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.
• Matching IV Placebo — OTHER
  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.

Study Details

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.

Key Dates

Start date

Aug 4, 2025

Status verified

Jul 2025

Primary completion

Apr 30, 2027

Completion

Apr 30, 2027

Study Design

Enrollment

96 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Arms

• Experimental: IV Allopregnanolone (Allo) for Extinction Retention (Expt. 1)
  Arm 1 of Expt. 1 includes women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV Allo immediately after completion of extinction training.
• Placebo Comparator: IV Placebo for Extinction Retention (Expt. 1)
  Arm 2 of Expt. 1 includes women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV placebo immediately after completion of extinction training.
• Experimental: IV Allo for Reconsolidation Blockade (Expt. 2)
  Arm 1 of Expt. 2 will include women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV Allo immediately after reactivation of the conditioned aversive memory by exposure to one conditioned stimulus (CS+).
• Placebo Comparator: IV Placebo for Reconsolidation Blockade (Expt. 2)
  Arm 2 of Expt. 2 will include will include women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV placebo immediately after reactivation of the conditioned aversive memory by exposure to one conditioned stimulus (CS+).

Primary Outcome Measure

Experiment 1: Extinction retention [ Time Frame: Day 3 ]

Central Contacts

• Kristen Curran
  (617) 726-8508
  [email protected]

Locations (1)

Find similar trials in Boston, MA

Related Studies

• CO2 Reactivity as a Biomarker of Non-Response to Exposure-Based Therapy
  Recruiting · Jasper A. Smits · Boston, Massachusetts
• Mechanisms Underlying Efficacy of Prolonged Exposure
  Recruiting · Massachusetts General Hospital · Boston, Massachusetts
• Mental Health, Intellectual and Neurodevelopmental Disorder Detection With Artificial Intelligence Models
  Enrolling By Invitation · Psyrin Inc. · Brookline, Massachusetts
• Evaluation of a Trauma-Informed Partner Violence Intervention Program
  Enrolling By Invitation · Boston University · Boston, Massachusetts