Post-traumatic Stress Disorder
Conditions
Keywords
post-traumatic stress disorder
Brief summary
In this study, we propose to employ a randomized, double-blind, placebo-controlled, outpatient clinical trial to test the efficacy, safety, and tolerability of a 160 mg and 40 mg challenge of the mGlu2/3 agonist pomaglumetad methionil relative to placebo in modulating fear-potentiated startle response and behavior in adults with post-traumatic stress disorder (PTSD) (N=30). Each participant will receive a single dose of the study drug (40 mg vs 160 mg vs placebo in a 1:1:1 ratio).
Interventions
DRUGPomaglumetad Methionil 160mg
Pomaglumetad Methionil 160mg, one dose, one time
DRUGPomaglumetad Methionil 40mg
Pomaglumetad Methionil 40mg, one dose, one time
DRUGPlacebo
Placebo, one dose, one time
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Men and women between 18 and 60 years of age, any race * Primary, current Axis I diagnosis of post traumatic stress disorder (PTSD) according to Diagnostic and Statistical Manual of Mental Disorders - IV (DSM-IV) criteria * Able to provide written informed consent
Exclusion criteria
* Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia, schizoaffective disorder, bipolar disorder * History of moderate or severe traumatic brain injury (TBI) with loss of consciousness * Lifetime history of seizure disorder * Current diagnosis of obsessive-compulsive disorder (OCD) * Current diagnosis of bulimia nervosa or anorexia nervosa; or substance use disorder * Alcohol or drug abuse in the past 90 days, or dependence in the past year. * Individuals with a cumulative lifetime history of intravenous substance abuse longer than 1 year. * Severe dissociation, defined as a Clinician Administered Dissociative States Scale (CADSS) score greater than 60 at baseline * Patients with creatinine clearance \<60 milliliters (mL)/min (moderate renal impairment) * Current pregnancy or breast feeding; medical conditions that could interfere with correct interpretation of study data, i.e., individuals with the following medical conditions will be excluded: cancer in the past year, stroke, heart attack, angina, neurological disease (multiple sclerosis, epilepsy, Parkinson's disease), central nervous system (CNS) lesions including TBI with loss of consciousness, dementing illness, and/or liver or kidney disease. Patients with QT interval \>450 msec (males) and \>470 msec (females). * Participants who have started new medication regimen for PTSD within 3 months prior to study start and subjects taking fluoxetine * Current suicidality defined by emergent Columbia Suicide Severity Rating Scale (CSSRS)-defined suicidal behavior, a suicidal ideation score of 5 (indicating active suicidal ideation with specific plan and some level of intent) or 4 (indicating active suicidal ideation with some intent to act, without specific plan) on the CSSRS or in the absence of a CSSRS suicidal ideation score of 5 or 4 or CSSRS-defined suicidal behavior, if the investigator determines the patient to have a significant short-term risk for a suicide attempt. * Individuals with active suicidal risk, active self-mutilation or aggressive behavior with threatening behavior toward others within the past year, as judged by the Principal Investigator * Pregnant or lactating women * Legal and Financial: Current legal proceedings resulting from the traumatic events. People whose continued receipt of financial benefits is contingent upon maintaining PTSD symptoms or who are waiting for a decision concerning the receipt of financial benefits based upon PTSD symptoms
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Effect of 160mg and 40mg of Pomaglumetad Methionil | 6 months | To evaluate the effect of 160mg and 40mg challenge of the mGlu2/3 receptor agonist pomaglumetad methionil relative to placebo in mitigating fear-potentiated startle using the neutral-predictable-unpredictable fear-potentiated startle paradigm in adults with post-traumatic stress disorder (PTSD). The primary index of unpredictable fear will be the difference score between startle magnitude in safe and unpredictable conditions in the absence of the cue. |
Participant flow
Recruitment details
No Outcome Measures Analyzed; Study Terminated
Pre-assignment details
No Outcome Measures Analyzed; Study Terminated
Participants by arm
| Arm | Count |
|---|---|
| Placebo | 6 |
| 40 mg Poma | 4 |
| 160 mg Poma | 4 |
| Total | 14 |
Baseline characteristics
| Characteristic | Placebo | 40 mg Poma | 160 mg Poma | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 4 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 1 / 6 | 0 / 4 | 2 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 | 0 / 4 |
Outcome results
Primary
To Evaluate the Effect of 160mg and 40mg of Pomaglumetad Methionil
To evaluate the effect of 160mg and 40mg challenge of the mGlu2/3 receptor agonist pomaglumetad methionil relative to placebo in mitigating fear-potentiated startle using the neutral-predictable-unpredictable fear-potentiated startle paradigm in adults with post-traumatic stress disorder (PTSD). The primary index of unpredictable fear will be the difference score between startle magnitude in safe and unpredictable conditions in the absence of the cue.
Time frame: 6 months
Population: 10 patients were enrolled and data for these 10 patients was not analyzed. Assuming a 2-tailed test,power=0.80, alpha=0.05, a total sample size of 30 (10 per group) is required to detect a moderate differential effect size change of a 160mg or 40 mg dose of pomaglumated methionil relative to placebo.