Computational Assessment of GABA Receptor Modulation in PTSD

NCT06852469 | Recruiting Phase 4 FDA Drug

• 1 other identifier: MHBP-009-24S
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

A substantial majority of Veterans with posttraumatic stress disorder (PTSD) continue to suffer even with the best current medications. Progress in developing more effective medications is hampered by the substantial variability within Veterans with PTSD, meaning the most effective medication likely varies from individual to individual. New scientific tools to help identify distinct subgroups of Veterans with PTSD who are likely to respond to specific medications could help improve treatment in this population. Research has indicated that a specific subgroup of Veterans with PTSD with a high level of anxious arousal may benefit from medications which boost signaling of the neurotransmitter gamma-aminobutyric acid (GABA). This project aims to validate a clinical test to identify these individuals using new computational and neuroimaging methods combined with the medication lorazepam, a positive GABA modulator. The ultimate goal is to use these methods in future clinical trials of new medications to target the best treatments to individual Veterans with PTSD.

Conditions

Stress Disorders, Post-Traumatic

Keywords

Arousal; gamma-Aminobutyric Acid; Lorazepam; Neuroimaging; Stress Disorders, Post-Traumatic

Outcome Measures

Primary Outcomes (1)

• Dynamic inhibition during sensorimotor control

  A dynamic inhibition parameter will be computed for each participant and session using a proportional-derivative (PD) model of sensorimotor control performance on the rapid assessment of motor processing (RAMP) task.

  1.5 hours after dosing

Secondary Outcomes (2)

• Neural activity during sensorimotor control

  1.5 hours after dosing

• Change from baseline in the the Positive and Negative Affect Schedule - Expanded Form (PANAS X) Fear score

  Baseline, 1.5 hours after dosing

Study Arms (2)

Lorazepam 1 mg, then placebo

EXPERIMENTAL

Participants will first receive a single dose of lorazepam 1 mg on the first testing session. After a 1 week washout period, participants will then receive a single dose of placebo on the second testing session.

Drug: Lorazepam 1 mg tablet; Drug: Placebo tablet

Placebo, then lorazepam 1 mg

EXPERIMENTAL

Participants will first receive a single dose of placebo on the first testing session. After a 1 week washout period, participants will then receive a single dose of lorazepam 1 mg on the second testing session.

Drug: Lorazepam 1 mg tablet; Drug: Placebo tablet

Interventions

Lorazepam 1 mg tablet DRUG

Lorazepam is an oral medication which is FDA approved to treat anxiety.

Also known as: Ativan

Lorazepam 1 mg, then placebo; Placebo, then lorazepam 1 mg

Placebo tablet DRUG

Placebo will match the study drug in mode of administration, color, size, and taste.

Lorazepam 1 mg, then placebo; Placebo, then lorazepam 1 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veteran;
• years of age, inclusive;
• Participants must be willing to abstain from alcohol 24 hours prior to and 24 hours after the testing session;
• Participants must be able to participate and willing to give written informed consent and to comply with the study restrictions;
• (a) Current diagnosis of PTSD based on CAPS-5.

You may not qualify if:

• Has uncontrolled, clinically significant neurologic (including seizure disorders), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the subject to participate or potentially confound the study results;
• Pregnancy (assessed by urine test at time of screening and prior to administration of study medication) or lactation;
• Lifetime history of a chronic psychotic disorder or bipolar disorder type I as assessed by MINI;
• Current moderate or severe substance use disorder as assessed by MINI;
• Positive urine toxicology (drugs of abuse as determined by a positive urine test) at screening and before drug administration. Subjects who screen positive for THC will be given an opportunity to be included in the event of a negative urine test 2 weeks later. THC is not infrequently used for medicinal purposes and, in California, is legal for recreational use. Subjects who are positive for THC will therefore not be excluded, but will be retested to ensure that THC is unlikely to be influencing results;
• Self-report or observable signs of drug or alcohol intoxication or withdrawal;
• Current benzodiazepine or opioid use; other psychotropic medications are allowed as long as they are at a stable dose for at least 2 weeks and do not exhibit an unsafe interaction with the study medication;
• Current or recent use of any medication deemed by the study physician (Dr. Howlett) to exhibit an unsafe interaction with lorazepam;
• Past intolerance (including allergic) to lorazepam or another benzodiazepine;
• Active suicidal ideation or otherwise considered at high suicidal risk by trained study staff using the C-SSRS;
• History of a traumatic brain injury (TBI) resulting in loss of consciousness for more than 30 minutes;
• Volunteers who do not have sufficient command of the English language, or who have any other impairment that would prevent them from reading and understanding the informed consent form(s) and completing the study procedures including clinical testing;
• Any other reason why, per study physician, the subject should not participate in this study, including concomitant disease or condition that could interfere with, or for which the study drug might interfere with, the conduct of the study, or that would, in the opinion of the study physician, pose an unacceptable risk to the subject in this study.
• (a) Axis I disorder as assessed by MINI.
• Contraindication to magnetic resonance imaging.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Lorazepam; Tablets

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Jonathan R Howlett, MD

  VA San Diego Healthcare System, San Diego, CA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vitaliana R Vasquez, BA

CONTACT

(858) 642-1256; Vitaliana.Vasquez@va.gov

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Assignment will be balanced using a randomly permuted block design. Medication will be prepared and labeled by a research pharmacist not otherwise involved in the study, and both participant and study personnel will be blinded to the study drug being administered. In case of medical emergency, unblinding can be performed. The pharmacy will blind drug and placebo through identical encapsulation. Placebo will match the study drug in mode of administration, color, size, and taste.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Each included participant will be administered a dose of lorazepam 1 mg and placebo in a crossover design, with the order of lorazepam and placebo determined in double-blind, randomized fashion (using a randomly permuted block design), with a one-week washout period

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: February 28, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)