Safety Study of Riluzole to Treat Post-traumatic Stress Disorder (PTSD)

NCT02155829 | Completed Phase 1 Results DMC

• 1 other identifier: 380797
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine whether Riluzole is effective in the augmentation treatment of post-traumatic stress disorder (PTSD) that is experienced by Active Duty military service members and Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) veterans who have not had symptom reduction after one or more kinds of medications or therapies.

Conditions

PTSD

Keywords

PTSD; TBI; Riluzole; Rilutek; augmentation; supplement; double blinded; clinical trial; placebo; RCT; Randomized Control Trial

Outcome Measures

Primary Outcomes (1)

• Clinician Administered PTSD Scale (CAPS) Score

  CAPS is a 30-item structured interview that can be used to make current (past month) diagnoses of PTSD, make lifetime diagnoses of PTSD, and assess PTSD symptoms over the past week. A summed score of 17 items: Minimum Score: 0 (no symptoms) Maximum Score: 136 (very severe symptoms) Subscales: Subscale B (re-experiencing): items 1-5, a score of 0-40. Subscale C (avoidance): items 6-12, a score of 0-56. Subscale D (hyperarousal): items 13-17, a score of 0-40. CAPS scores were measured at baseline, mid-treatment, and post-treatment. For outcome analyses, differences between pre-treatment and post-treatment scores were used.

  Week 1 and 8

Secondary Outcomes (6)

• PTSD Check List Specific (PCL-S)

  Week 1 and 8

• Montgomery-Åsberg Depression Rating Scale (MADRS) Score

  Week 1 and 8

• Hamilton Anxiety Rating Scale (HAM-A)

  Week 1 and 8

• Sheehan Disability Scale (SDS) Score

  Week 1 and 8

• Clinician Administered PTSD Subscale D (CAPS-D)

  Week 1 and 8

Other Outcomes (1)

• NAA/Cr Ratio

  Measured at study start (Week 0) for baseline and measured at study completion (Week 8)

Study Arms (2)

Riluzole

EXPERIMENTAL

Weeks 1 and 2: Riluzole 50 mg tablet by mouth every 12 hours (100 mg/day) for 2-weeks Weeks 3 to 8 (optional dose increase): 2 Riluzole 50 mg tablets by mouth every 12 hours (200 mg/day) for 6-weeks

Drug: Riluzole

Placebo

PLACEBO COMPARATOR

Weeks 1 and 2: Placebo 50 mg tablet by mouth every 12 hours (100 mg/day) for 2-weeks Weeks 3 to 8 (optional dose increase): 2 Placebo 50 mg tablets by mouth every 12 hours (200 mg/day) for 6-weeks

Drug: Placebo (for Riluzole)

Interventions

Riluzole DRUG

Also known as: Rilutek

Riluzole

Placebo (for Riluzole) DRUG

Also known as: Inert tablet manufactured to be indistinguishable from a Riluzole 50 mg tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Active-duty service member or an Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), or Operation New Dawn (OND) veteran.
• Clinical diagnosis of PTSD and have not achieved remission with an adequate trial of medication treatment (8 weeks) as indicated by self-report at referral and confirmed by baseline CAPS score of greater than or = to 40 after informed consent is obtained.

You may not qualify if:

• Female subjects of childbearing capacity who test positively for ß-HCG, or are either self-reporting as pregnant, planning to become pregnant, or nursing.
• Presence of psychotic features.
• Unable to provide informed consent or comply with study procedures.
• Previous treatment with riluzole.
• Serious, unstable illnesses including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, hematologic disease, or HIV. This includes individuals with a history of COPD by diagnosis as well as persons taking inhalers for Asthma or Reactive Airway Disease.
• Clinically significant abnormal levels (3x ULN or greater) of serum transaminases (ALT/SGPT; AST/SGOT), current or past blood dyscrasia.
• Subjects with uncorrected hypothyroidism or hyperthyroidism.
• DSM-IV alcohol or substance abuse or dependence within 90 days of the screening visit.
• Treatment with a reversible MAOI, guanethidine, or guanadrel within 1 week, or any change in fluoxetine dosing within 8 weeks prior to visit 2. Use of antidepressant and sedative/hypnotic drugs at stable dose is permitted.
• Documented history of hypersensitivity or intolerance to riluzole.
• Subjects with a current or past history of other axis I disorders including schizophrenia, schizoaffective disorder, bipolar disorder or dementia. However, those with a co-morbid history of other Axis I disorder like major depression, dysthymia or other anxiety disorders will be included; the justification for this is that approximately 70% of subjects with PTSD have co-morbid depression and or alcohol abuse, and restricting the sample to PTSD patients without depression will not accurately reflect the scope of this disorder.
• Patients who are currently at high risk for homicide or suicide, as indicated by an affirmative answer to the question: "In the last three months, have you attempted to kill yourself, made specific plans to kill yourself, or had the intention to kill yourself?"
• Current or planned litigation regarding the traumatic event.
• Patients who recently started trauma focused cognitive behavioral psychotherapy (Patient's underlying educational or supportive individual or group therapy will be included).
• Patient's actively enrolled in an evidence based psychotherapy treatment (e.g., Cognitive Processing Therapy or Prolonged Exposure Therapy) will be excluded until that therapy has concluded, but may be re-approached at that time if patient self-report or clinician referral suggests persistent PTSD symptoms upon conclusion of that treatment.

Sponsors & Collaborators

• Uniformed Services University of the Health Sciences: lead
• U.S. Army Medical Research and Development Command: collaborator

Study Sites (2)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20814, United States

Location

Syracuse VA Medical Center, Center for Integrated Healthcare (116C)

Syracuse, New York, 13210, United States

Location

Related Publications (1)

• Spangler PT, West JC, Dempsey CL, Possemato K, Bartolanzo D, Aliaga P, Zarate C, Vythilingam M, Benedek DM. Randomized Controlled Trial of Riluzole Augmentation for Posttraumatic Stress Disorder: Efficacy of a Glutamatergic Modulator for Antidepressant-Resistant Symptoms. J Clin Psychiatry. 2020 Oct 27;81(6):20m13233. doi: 10.4088/JCP.20m13233.

  PMID: 33113596 DERIVED

Related Links

• Study conducted by the Center for the Study of Traumatic Stress

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Riluzole; Tablets

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

Result limited to combat-related PTSD in military and veterans of recent conflict.

Results Point of Contact

• Title: Dr. David M. Benedek
• Organization: USUHS

david.benedek@usuhs.edu

(301) 295-3294

Study Officials

• David M Benedek, MD

  USUHS, WRNMMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 15, 2013
• First Posted: June 4, 2014
• Study Start: July 1, 2013
• Primary Completion: October 30, 2017
• Study Completion: November 30, 2017
• Last Updated: May 24, 2021
• Results First Posted: September 25, 2020

Record last verified: 2021-04

Locations

US (2)