Computational Assessment of GABA Receptor Modulation in PTSD
ConditionStress Disorders, Post-Traumatic
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-65
SponsorVA Office of Research and Development
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Veteran;
18-65 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;
Disqualifiers
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;
Trial design
Design model
Crossover
Treatments tested in this trial
Lorazepam 1 mg tablet
DrugLorazepam is an oral medication which is FDA approved to treat anxiety.
Placebo tablet
DrugPlacebo will match the study drug in mode of administration, color, size, and taste.
Treatment groups
150 Participants
are divided into 2 treatment groupsGroup A: Lorazepam 1 mg, then placeboExperimental treatment 2 interventions
Group B: Placebo, then lorazepam 1 mgExperimental treatment 2 interventions
Trial outcomes
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.
Time frame
1.5 hours after dosingSecondary outcomes
1
Neural activity during sensorimotor control
Blood oxygen level dependent (BOLD) response in the dorsal anterior cingulate cortex (dACC), insula, and amygdala (defined according to the Harvard-Oxford anatomical atlas) and in the whole brain will be measured during sensorimotor control performance on the rapid assessment of motor processing (RAMP) task. Bonferroni corrections will be performed based on the number of regions-of-interest (ROIs).
Time frame
1.5 hours after dosing2
Change from baseline in the the Positive and Negative Affect Schedule - Expanded Form (PANAS X) Fear score
The change from baseline in the PANAS X Fear score will be measured. The PANAS X Fear subscale consists of 6 items. Items are answered on a 5 point scale, 1 (very slightly or not at all) to 5 (extremely). PANAS X Fear scores range from 6-30, with higher scores representing higher levels of fear.
Time frame
Baseline, 1.5 hours after dosingSponsors and contacts
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Source ClinicalTrials.gov