Trial Outcomes & Findings for Safety Study of Riluzole to Treat Post-traumatic Stress Disorder (PTSD) (NCT NCT02155829)

NCT ID: NCT02155829

Last Updated: 2021-05-24

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 75 participants
• Primary outcome timeframe: Week 1 and 8
• Results posted on: 2021-05-24

Participant Flow

Recruitment from WRNMMC = Walter Reed National Military Medical Center ; SVAMC = Syracuse Veterans Administration Medical Center

Participant milestones

Measure	Riluzole 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	Placebo 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
Overall Study STARTED	37	38
Overall Study COMPLETED	31	35
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Measure	Riluzole 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	Placebo 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
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	3	3
Overall Study Protocol Violation	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Riluzole n=36 Participants 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 Riluzole	Placebo n=38 Participants 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 Placebo (for Riluzole)	Total n=74 Participants Total of all reporting groups
Age, Continuous	37.4 years STANDARD_DEVIATION 8.9 • n=5 Participants	38.1 years STANDARD_DEVIATION 8.2 • n=7 Participants	37.8 years STANDARD_DEVIATION 8.5 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	32 Participants n=7 Participants	63 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	33 Participants n=7 Participants	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants	25 Participants n=7 Participants	51 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Clinician Administered PTSD Scale - IV	70.6 units on a scale STANDARD_DEVIATION 19.8 • n=5 Participants	62.4 units on a scale STANDARD_DEVIATION 16.9 • n=7 Participants	66.4 units on a scale STANDARD_DEVIATION 18.7 • n=5 Participants

PRIMARY outcome

Timeframe: Week 1 and 8

Population: One participant failed to meet minimum Clinician-Administered PTSD Scale IV (CAPS-IV) score for inclusion at phase 2 baseline and was excluded from intent-to treat (ITT) analyses.

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.

Outcome measures

Measure	Riluzole n=36 Participants 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 Riluzole	Placebo n=38 Participants 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 Placebo (for Riluzole)
Clinician Administered PTSD Scale (CAPS) Score	-21.1 score on a scale Standard Deviation 18.9	-16.7 score on a scale Standard Deviation 17.2

SECONDARY outcome

Timeframe: Week 1 and 8

Population: One participant failed to meet minimum Clinician-Administered PTSD Scale IV (CAPS-IV) score for inclusion at phase 2 baseline and was excluded from intent-to treat (ITT) analyses.

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.

Outcome measures

Measure	Riluzole n=36 Participants 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 Riluzole	Placebo n=38 Participants 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 Placebo (for Riluzole)
PTSD Check List Specific (PCL-S)	-15.4 score on a scale Standard Deviation 13.5	-14.5 score on a scale Standard Deviation 11.4

SECONDARY outcome

Timeframe: Week 1 and 8

Population: One participant failed to meet minimum Clinician-Administered PTSD Scale IV (CAPS-IV) score for inclusion at phase 2 baseline and was excluded from intent-to treat (ITT) analyses.

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.

Outcome measures

Measure	Riluzole n=36 Participants 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 Riluzole	Placebo n=38 Participants 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 Placebo (for Riluzole)
Montgomery-Åsberg Depression Rating Scale (MADRS) Score	-7.9 score on a scale Standard Deviation 7.6	-8.2 score on a scale Standard Deviation 9.6

SECONDARY outcome

Timeframe: Week 1 and 8

Population: One participant failed to meet minimum Clinician-Administered PTSD Scale IV (CAPS-IV) score for inclusion at phase 2 baseline and was excluded from intent-to treat (ITT) analyses.

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.

Outcome measures

Measure	Riluzole n=36 Participants 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 Riluzole	Placebo n=38 Participants 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 Placebo (for Riluzole)
Hamilton Anxiety Rating Scale (HAM-A)	-7.8 score on a scale Standard Deviation 7.4	-6.7 score on a scale Standard Deviation 6.9

SECONDARY outcome

Timeframe: Week 1 and 8

Population: One participant failed to meet minimum Clinician-Administered PTSD Scale IV (CAPS-IV) score for inclusion at phase 2 baseline and was excluded from intent-to treat (ITT) analyses.

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.

Outcome measures

Measure	Riluzole n=36 Participants 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 Riluzole	Placebo n=38 Participants 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 Placebo (for Riluzole)
Sheehan Disability Scale (SDS) Score	-6.3 score on a scale Standard Deviation 6.8	-5.7 score on a scale Standard Deviation 5.9

SECONDARY outcome

Timeframe: Week 1 and 8

Population: One participant failed to meet minimum Clinician-Administered PTSD Scale IV (CAPS-IV) score for inclusion at phase 2 baseline and was excluded from intent-to treat (ITT) analyses.

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.

Outcome measures

Measure	Riluzole n=36 Participants 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 Riluzole	Placebo n=38 Participants 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 Placebo (for Riluzole)
Clinician Administered PTSD Subscale D (CAPS-D)	-6.8 score on a scale Standard Deviation 8.2	-3.7 score on a scale Standard Deviation 7.3

SECONDARY outcome

Timeframe: Week 1 and week 8

Population: One participant failed to meet minimum Clinician-Administered PTSD Scale IV (CAPS-IV) score for inclusion at phase 2 baseline and was excluded from intent-to treat (ITT) analyses.

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.

Outcome measures

Measure	Riluzole n=36 Participants 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 Riluzole	Placebo n=38 Participants 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 Placebo (for Riluzole)
PTSD Checklist - D (PCL-D)	-5.9 score on a scale Standard Deviation 5.6	-3.4 score on a scale Standard Deviation 4.9

OTHER_PRE_SPECIFIED outcome

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

The N-acetyl aspartate to creatine ratio (NAA/Cr) in the hippocampus and anterior cingulate, measured using magnetic resonance spectroscopy (1H MRS), will be evaluated for change after 8-week treatment with riluzole.

Outcome measures

Outcome data not reported

Adverse Events

Riluzole

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Riluzole n=37 participants at risk 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	Placebo n=38 participants at risk 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
Gastrointestinal disorders Gastrointestinal Symptoms	5.4% 2/37 • Number of events 2 • 10 weeks	0.00% 0/38 • 10 weeks
Hepatobiliary disorders LFT Elevation	5.4% 2/37 • Number of events 2 • 10 weeks	0.00% 0/38 • 10 weeks
Psychiatric disorders Clinical deterioration	2.7% 1/37 • Number of events 1 • 10 weeks	0.00% 0/38 • 10 weeks

Additional Information

Dr. David M. Benedek

USUHS

Phone: (301) 295-3294

Email: david.benedek@usuhs.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place