PTSDPhase 1/2NCT02155829
Safety Study of Riluzole to Treat Post-traumatic Stress Disorder (PTSD)
A Phase 1/2 study testing Riluzole in people with PTSD, run by Uniformed Services University of the Health Sciences at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- PTSD
- What is being tested?
- Riluzole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2013to 30 Nov 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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.
- Subjects with an artificial cardiac pacemaker or metallic implants within their body will be enrolled at WRNMMC for the placebo-control clinical trial portion of the study only. These individuals, due to their pre-existing medical condition, are medically ineligible to participate in the 1H MRS imaging portion of the study. Further, the Magnetic Resonance (MRI) Screening Form is use at WRNMMC will be used for participant screening prior to any imaging procedures.
- Use of benzodiazepines.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Walter Reed National Military Medical Center
Bethesda, Maryland, 20814
Syracuse VA Medical Center, Center for Integrated Healthcare (116C)
Syracuse, New York, 13210
About this study
Official title: Riluzole for PTSD: Efficacy of a Glutamatergic Modulator as Augmentation Treatment for Posttraumatic Stress Disorder
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.
Read the detailed description
Riluzole is a glutamatergic modulator that inhibits glutamate release and enhances AMPA trafficking and clearance of excessive synaptic glutamate resulting in neuroprotective properties. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis (ALS) and has been found to have antidepressant and anxiolytic properties in animals and in humans (Zarate et al., 2004). Posttraumatic stress disorder (PTSD) is a chronic and seriously debilitating anxiety disorder that develops following exposure to severe trauma, such as combat exposure. Structural magnetic resonance imaging has been used to measure the volume of crucial structures implicated in the pathophysiology of PTSD, with several morphometric studies confirming smaller hippocampal volume in PTSD patients. Current pharmacological treatment for PTSD, and particularly combat-related PTSD, is suboptimal. Drugs that alter neuronal survival pathways through reduction of glutamate activity may play a role in reversing the loss of neuronal integrity and possible focal atrophy in regions of the brain implicated in the pathophysiology of PTSD, potentially improving the symptoms of PTSD, as well as TBI. This study will evaluate the efficacy of acute riluzole treatment in active duty and Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), and Operation New Dawn (OND) veterans with PTSD, with or without mild TBI (mTBI), who are sub-optimally responsive to other medication treatments. A total of 158 active duty and OIF, OEF and OND veterans, aged 18 to 65 will be enrolled from WRNMMC and the Syracuse VA Medical Center to participate in this 8-week randomized, double- blind, placebo-controlled, parallel study. Patients who are suboptimal responders to their current psychotropic drugs will continue these at stable dosage for at least 2 weeks prior to randomization during the screening period. We hypothesize that those subjects with PTSD, with or without mTBI, who are only partially responsive to initial therapy and are subsequently randomized to augmentation therapy with Riluzole (100-200mg/day) will have a superior response rate compared to those subjects randomized to placebo.
- Conditions
- PTSD
- Being tested
- Riluzole, Placebo (for Riluzole)
- Keywords
- PTSD, TBI, Riluzole, Rilutek, augmentation, supplement, double blinded, clinical trial, placebo, RCT, Randomized Control Trial
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiluzoleDrug
Also called Rilutek
Placebo (for Riluzole)Drug
Also called Inert tablet manufactured to be indistinguishable from a Riluzole 50 mg tablet
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Placebo (for Riluzole) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 1 and 8
Secondary outcomes (6)
PTSD Check List Specific (PCL-S)
A 17-item self-report measure used to assess PTSD symptoms related to a specific traumatic event.
Scoring: A sum of all 17 items. Minimum: 17 (no symptoms) Maximum: 85 (very severe symptoms)
PCL-S scores were measured at every study visit. For outcome analyses, differences between pre-treatment and post-treatment scores were used.
Measured: Week 1 and 8
Montgomery-Åsberg Depression Rating Scale (MADRS) Score
A ten-item diagnostic questionnaire to measure the severity of depressive episodes.
Scoring: A sum of all 10 items. Minimum: 0 (no symptoms) Maximum: 60 (very severe symptoms)
MADRS scores were measured at every study visit. For outcome analyses, differences between pre-treatment and post-treatment scores were used.
Measured: Week 1 and 8
Hamilton Anxiety Rating Scale (HAM-A)
A 14-item clinician-administered assessment measuring anxiety symptoms.
Scoring: A sum of all 14 items. Minimum: 0 (no symptoms) Maximum: 56 (very severe symptoms)
HAM-A scores were measured at baseline, mid-treatment, and post-treatment. For outcome analyses, differences between pre-treatment and post-treatment scores were used.
Measured: Week 1 and 8
Sheehan Disability Scale (SDS) Score
A 3-item self-report measure to assess functional impairment in work/school, social, and family life.
Scoring: A sum of all 3 items. Minimum: 0 (no symptoms) Maximum: 30 (very severe symptoms)
SDS scores were measured at baseline, mid-treatment, and post-treatment. For outcome analyses, differences between pre-treatment and post-treatment scores were used.
Measured: Week 1 and 8
Clinician Administered PTSD Subscale D (CAPS-D)
Subscale D (items 13-17 on the CAPS-IV) measures Hyperarousal symptoms of PTSD
Scoring: A sum of items 13-17. Minimum: 0 (no symptoms) Maximum: 40 (very severe symptoms)
CAPS-D scores were measured at baseline, mid-treatment, and post-treatment. For outcome analyses, differences between pre-treatment and post-treatment scores were used.
Measured: Week 1 and 8
PTSD Checklist - D (PCL-D)
The subscale D (items 13-17 on the PCL) measures hyperarousal symptoms of PTSD. Scoring: A sum of items 13 to 17. Minimum: 5 (no symptoms) Maximum: 25 (very severe symptoms)
PCL-D scores were measured at baseline, mid-treatment, and post-treatment. For outcome analyses, differences between pre-treatment and post-treatment scores were used.
Measured: Week 1 and week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2014 (estimated)
- Study startJul 2013
- Primary completion30 Oct 2017
- Study completion30 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uniformed Services University of the Health Sciences
- Sponsor type
- US federal agency
- Collaborators
- U.S. Army Medical Research and Development Command
- Responsible party
- Principal investigator, David M. Benedek, Uniformed Services University of the Health Sciences
- Investigators
- David M Benedek, MD, Principal investigator, USUHS, WRNMMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02155829
- Sponsor's protocol ID
- 380797
- Status last verified
- Apr 2021
- First submitted
- 15 Nov 2013
- Last updated
- 24 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 33113596
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Riluzole for PTSD: Efficacy of a Glutamatergic Modulator as Augmentation Treatment for Posttraumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT02155829
- Acronym / sponsor ID
- 380797
- Conditions
- PTSD
- Keywords
- PTSD, TBI, Riluzole, Rilutek, augmentation, supplement, double blinded, clinical trial
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Uniformed Services University of the Health SciencesUS federal agency
- Collaborators
- U.S. Army Medical Research and Development Command
- Study start
- Jul 2013
- Primary completion
- 30 Oct 2017 (actual)
- Study completion
- 30 Nov 2017 (actual)
- First posted
- 4 Jun 2014 (estimated)
- Results
- Posted 25 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Riluzole is a glutamatergic modulator that inhibits glutamate release and enhances AMPA trafficking and clearance of excessive synaptic glutamate resulting in neuroprotective properties. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis (ALS) and has been found to have antidepressant and anxiolytic properties in animals and in humans (Zarate et al., 2004). Posttraumatic stress disorder (PTSD) is a chronic and seriously debilitating anxiety disorder that develops following exposure to severe trauma, such as combat exposure. Structural magnetic resonance imaging has been used to measure the volume of crucial structures implicated in the pathophysiology of PTSD, with several morphometric studies confirming smaller hippocampal volume in PTSD patients. Current pharmacological treatment for PTSD, and particularly combat-related PTSD, is suboptimal. Drugs that alter neuronal survival pathways through reduction of glutamate activity may play a role in reversing the loss of neuronal integrity and possible focal atrophy in regions of the brain implicated in the pathophysiology of PTSD, potentially improving the symptoms of PTSD, as well as TBI. This study will evaluate the efficacy of acute riluzole treatment in active duty and Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), and Operation New Dawn (OND) veterans with PTSD, with or without mild TBI (mTBI), who are sub-optimally responsive to other medication treatments. A total of 158 active duty and OIF, OEF and OND veterans, aged 18 to 65 will be enrolled from WRNMMC and the Syracuse VA Medical Center to participate in this 8-week randomized, double- blind, placebo-controlled, parallel study. Patients who are suboptimal responders to their current psychotropic drugs will continue these at stable dosage for at least 2 weeks prior to randomization during the screening period. We hypothesize that those subjects with PTSD, with or without mTBI, who are only partially responsive to initial therapy and are subsequently randomized to augmentation therapy with Riluzole (100-200mg/day) will have a superior response rate compared to those subjects randomized to placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Riluzole | Experimental | Drug: RiluzoleWeeks 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 |
| Placebo | Placebo comparator | Drug: Placebo (for Riluzole)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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RiluzoleAlso: Rilutek | Drug | Riluzole |
| Placebo (for Riluzole)Also: Inert tablet manufactured to be indistinguishable from a Riluzole 50 mg tablet | Drug | Placebo |
Primary outcome
Clinician Administered PTSD Scale (CAPS) Score
Time frame: Week 1 and 8
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.
6 secondary outcomes
PTSD Check List Specific (PCL-S)
Time frame: Week 1 and 8
Montgomery-Åsberg Depression Rating Scale (MADRS) Score
Time frame: Week 1 and 8
Hamilton Anxiety Rating Scale (HAM-A)
Time frame: Week 1 and 8
Sheehan Disability Scale (SDS) Score
Time frame: Week 1 and 8
Clinician Administered PTSD Subscale D (CAPS-D)
Time frame: Week 1 and 8
PTSD Checklist - D (PCL-D)
Time frame: Week 1 and week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33113596Spangler 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.
- Study conducted by the Center for the Study of Traumatic StressLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David M Benedek, MD principal investigator
USUHS, WRNMMC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Riluzole in people with PTSD, run by Uniformed Services University of the Health Sciences at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinician Administered PTSD Scale (CAPS) Score (time frame: Week 1 and 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02155829, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2021.