RecruitingPhase 2NCT04468360

Facilitation of Extinction Retention and Reconsolidation Blockade in PTSD

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

Sponsor

Boston University

Enrollment

256 participants

Start Date

Mar 4, 2022

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): 1. promotes consolidation of extinction learning (sub-study 1) or 2. blocks reconsolidation 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 a medication called allopregnanolone (a naturally occurring brain hormone) to see if it can help people with PTSD by enhancing the brain's ability to "unlearn" fear memories. This approach targets the root cause of PTSD — difficulty letting go of traumatic memories. **You may be eligible if:** - You have been diagnosed with chronic PTSD - You are generally healthy and not taking medications that could interfere with the study - You are willing to abstain from alcohol (2 weeks) and other substances (4 weeks) before and during the study - Females: you must have a regular menstrual cycle and not be on most forms of hormonal birth control **You may NOT be eligible if:** - You have bipolar I disorder, schizophrenia, or significant psychotic symptoms - You have a moderate or severe substance use disorder in the last 3 months - You have untreated sleep apnea - You have attempted suicide within the past year or are at imminent risk of harm - You have a moderate or severe traumatic brain injury - You are pregnant or breastfeeding - You wear hearing aids or fail a hearing test - You have a medical condition that could affect the results or your safety 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

BEHAVIORAL3-day differential fear conditioning, extinction, and extinction retention testing paradigm

Day 1: Fear acquisition involving the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a conditioned stimuli (CS) (Expts. 1 and 2). The CS will be different colored shapes appearing on a computer monitor. An auditory stimulus will serve as the startle probe. Day 2: Either extinction training (Expt. 1) or fear memory reactivation by a single CS+ with no US (Expt. 2) will occur followed by IV Allo vs. IV placebo administration. Day 3: The effects of IV Allo vs. IV placebo (administered on Day 2) on extinction retention (Expt. 1) or reconsolidation blockade (Expt. 2), as well as reinstatement of conditioned fear (Expts. 1 and 2) will be assessed.

DRUGAllopregnanolone (Allo) with Dexolve in 0.9% saline for injection manufactured by University of California, Davis

Expt. 1 (extinction retention): On Day 2, a 1.7 ug/kg IV bolus of Allo will be administered over 5 minutes at the completion of extinction training and continued as a 5-hour drip to maintain resting plasma Allo levels at \~1500 pg/ml. Expt. 2 (reconsolidation blockade): On Day 2, a 28 ug/kg IV bolus of Allo will be infused over 30 minutes immediately following presentation of a single CS+.

OTHERMatching IV Placebo

Expt. 1 (extinction retention): On Day 2, a 1.7 ug/kg IV bolus of the matching placebo formulation will be administered over 5 minutes at the completion of extinction training and continued as a 5-hour drip to maintain resting plasma Allo levels at \~1500 pg/ml. Expt. 2 (reconsolidation blockade): On Day 2, a 28 ug/kg IV bolus of the matching placebo formulation will be infused over 30 minutes immediately following presentation of a single CS+.