A mGlu2/3 Agonist in the Treatment of PTSD

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).

Study Overview

• Status: Terminated
• Conditions: Post-traumatic Stress Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Pomaglumetad Methionil 40mg; Drug: Pomaglumetad Methionil 160mg

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo, one dose	Drug: Placebo; Placebo, one dose, one time
Experimental: Pomaglumetad Methionil 40mg; Pomaglumetad Methionil 40mg, one dose, one time	Drug: Pomaglumetad Methionil 40mg; Pomaglumetad Methionil 40mg, one dose, one time; Other Names: LY2140023
Experimental: Pomaglumetad Methionil 160mg; Pomaglumetad Methionil 160mg, one dose, one time	Drug: Pomaglumetad Methionil 160mg; Pomaglumetad Methionil 160mg, one dose, one time; Other Names: LY2140023

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Charles Marmar, MD, NYU School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): February 11, 2016
• Study Completion (Actual): September 11, 2016

Study Registration Dates

• First Submitted: September 3, 2014
• First Submitted That Met QC Criteria: September 4, 2014
• First Posted (Estimate): September 9, 2014

Study Record Updates

• Last Update Posted (Actual): November 2, 2018
• Last Update Submitted That Met QC Criteria: March 8, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: post-traumatic stress disorder
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: 13-00609

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No