A mGlu2/3 Agonist in the Treatment of PTSD

• Sponsor: NYU Langone Health (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02234687
• Collaborator: (none)
• Enrollment: 10
• Arms: 3
• Actual Duration (Months): 24.3

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Post-traumatic Stress Disorder	Drug: Pomaglumetad Methionil 160mg; Drug: Pomaglumetad Methionil 40mg; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A mGlu2/3 Agonist in the Treatment of PTSD
• Actual Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Feb 11, 2016
• Actual Study Completion Date: Sep 11, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• NYU Langone Health

Investigators

• Principal Investigator: Charles Marmar, MD, NYU School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT02234687
• Other Study ID Numbers: 13-00609
• First Posted: Sep 9, 2014
• Last Update Posted: Nov 2, 2018
• Last Verified: Mar 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by NYU Langone Health: post-traumatic stress disorder
• Additional relevant MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic

Study Results

Participant Flow

Recruitment Details	No Outcome Measures Analyzed; Study Terminated
Pre-assignment Detail	No Outcome Measures Analyzed; Study Terminated

Arm/Group Title	40 mg Poma	Placebo	160 mg Poma
Arm/Group Description	Study Terminated. No outcome measures were analyzed	Study Terminated. No outcome measures were analyzed	Study Terminated. No outcome measures were analyzed
Period Title: Overall Study
STARTED	6	4	4
COMPLETED	0	0	0
NOT COMPLETED	6	4	4

Baseline Characteristics

Arm/Group Title	Placebo	40 mg Poma	160 mg Poma	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	6	4	4	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	4 100%	4 100%	14 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 50%	2 50%	2 50%	7 50%
Male	3 50%	2 50%	2 50%	7 50%

Outcome Measures

1. Primary Outcome

Title	To Evaluate the Effect of 160mg and 40mg of Pomaglumetad Methionil
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Pomaglumetad Methionil 160mg	Pomaglumetad Methionil 40mg
Arm/Group Description	Placebo: Placebo, one dose, one time	Pomaglumetad Methionil 160mg, one dose, one time Pomaglumetad Methionil 160mg: Pomaglumetad Methionil 160mg, one dose, one time	Pomaglumetad Methionil 40mg, one dose, one time Pomaglumetad Methionil 40mg: Pomaglumetad Methionil 40mg, one dose, one time
Measure Participants	0	0	0

Adverse Events

Time Frame	6 Months
Arm/Group Title	Placebo		Pomaglumetad Methionil 160mg		Pomaglumetad Methionil 40mg
Arm/Group Description	Placebo, one dose Placebo: Placebo, one dose, one time		Pomaglumetad Methionil 160mg, one dose, one time		Pomaglumetad Methionil 40mg, one dose, one time
All Cause Mortality
	Placebo		Pomaglumetad Methionil 160mg		Pomaglumetad Methionil 40mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/4 (0%)		0/4 (0%)
Serious Adverse Events
	Placebo		Pomaglumetad Methionil 160mg		Pomaglumetad Methionil 40mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Pomaglumetad Methionil 160mg		Pomaglumetad Methionil 40mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/4 (0%)		2/4 (50%)
Gastrointestinal disorders
Vomiting after receiving medication	0/6 (0%)	0	0/4 (0%)	0	2/4 (50%)	2
General disorders
PTSD symptoms became worse after the study	1/6 (16.7%)	1	0/4 (0%)	0	0/4 (0%)	0

Limitations/Caveats

10 patients were enrolled and data for these 10 patients was not analyzed because enrollment must reach a certain threshold for reporting.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.