Riluzole in the Treatment of Spasticity in the Traumatic Chronic Spinal Cord Injury Condition (RILUSCI)

Riluzole in the Treatment of Spasticity in the Traumatic Chronic Spinal Cord Injury Condition: Adaptive, Multicenter, Placebo-controlled, Randomised, Double Blind Trial in a Rare Disorder

The study will be conducted in two steps:

1. Determination of the Minimal Effective Dose (MED) among the four doses of the panel
2. Estimation of the probability of response associated to the MED.

Each step has a main objective:

Step 1 Objective: To determine a daily dose of Riluzole that improves spasticity in patients with chronic SCI

Step 2 Objective: To demonstrate, in a phase 2b trial, the efficacy of Riluzole to improve spasticity vs placebo, in patients with chronic SCI.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injury
• Intervention / Treatment: Drug: Placebo; Biological: Blood Samples; Drug: Riluzole

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: OLIVIER BLIN; Email: olivier.blin@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Contact: OLIVIER BLIN; Email: olivier.blin@ap-hm.fr
    • Principal Investigator: jean-michel VITON

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Chronic traumatic SCI defined as:

   a. At least a 12-month history of:

   i. C4-T12 traumatic SCI

   ii. Complete and incomplete ( AIS A,B,C,D)

   iii. With Spasticity (5>MAS>1 on at least adductor muscles and/or triceps surae muscles and NRS ≥ 4)

2. Male or Female
3. Aged 18 to 65 years at the time of screening
4. Judged by site investigator to be able to comply with evaluations at baseline and throughout the study
5. Last injection of BTX-A in striated muscle more than 3 months ago and patients must have returned to their level of spasticity before BTX-A injection
6. Last intrathecal (IT) injection of baclofen or per os administration of any myorelaxant should be more than 14 days ago (Step 1)
7. The dose of myorelaxant or Baclofen should be stable for ≥ 30 days prior to screening and kept at stable daily dose until the end of the protocol (Step 2).
8. Stable on all other chronic medications for ≥ 30 days prior to screening, including analgesics
9. Stable on rehabilitation (methods and frequency) for ≥ 15 days prior to screening
10. Written informed consent provided by subject

Exclusion Criteria:

1. Spinal cord injury of less than 12 months,
2. Associated Brain lesion that might be the cause of spasticity,
3. MAS≤1 or =5 on at least adductor muscles and/or triceps surae muscles or NRS < 4
4. Presence of urinary infection, fever, pressure ulcer or other spasticity-aggravating factors.
5. Presence of other significant neurological or mental disorder or other illness, which would preclude accurate evaluation,
6. Recent history (less than 1 year) of chemical substance dependency or significant psychosocial disturbance,
7. Insufficient fluency in local language to complete neuropsychological, global and spasticity assessments
8. Active liver disease or clinical jaundice
9. Active malignancy or history of invasive malignancy within the last five years
10. Neutropenia, liver enzymes (ALT/SGPT or AST/SGOT) 2 times the upper limit of normal (ULN) at screening visit, baseline elevations of several liver function tests (especially elevated bilirubin).
11. AIDS or AIDS-related complex,
12. The systolic blood pressure measurement is > 190 or < 85 mm Hg and/or the diastolic blood pressure measurement is > 105 or < 50 mm Hg at screening.
13. The ECG is abnormal at screening and judged to be clinically significant by the site investigator. Particular attention will be given to any sign suggesting conduction disorders.
14. Treatment with any investigational drugs or device within 60 days of screening
15. Any myorelaxant medication including IT baclofen, taken by the subject in the last 14 days prior to screening (step 1)
16. Not stable under IT baclofen or per os myorelaxant medication for at least 30 days prior screening (step 2)
17. Not stable on all other chronic medications for ≥ 30 days prior to screening, including analgesics
18. Injection of BTX-A in striated muscle less than 3 months ago
19. Subject is currently using, and will continue to use for the next 14 days any of the following medications which are classified as Inhibitors of CYP 1A2 (e.g. diclofenac, diazepam, nicergoline, clomipramine, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline and quinolones) or Inducers of CYP 1A2 (e.g. rifampicin and omeprazole)
20. Ongoing pregnancy or lactation. Women with childbearing potential not using any form of efficacious contraception.
21. Known hypersensitivity to Riluzole

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; placebo capsules 25 or 50 mg; Biological: Blood Samples; v1;v2;v3;v4
Experimental: Experimental	Biological: Blood Samples; v1;v2;v3;v4; Drug: Riluzole; Riluzole capsules (25 or 50 mg) will be administered in the four dose level groups (i.e. 25 mg bid; 50 mg bid; 75 mg bid; 100 mg bid).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the Minimum Effective Dose (MED) of Riluzole	Blood Sample	2 Months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: OLIVIER BLIN, Assistance Publique Hopitaux de Marseille; Principal Investigator: JEAN MICHEL VITON, Assistance Publique Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2019
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimate): August 9, 2016

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neuroprotective Agents; Protective Agents; Anticonvulsants; Riluzole
• Other Study ID Numbers: 2016-000901-35; 2016-02 (Other Identifier: ap hm)

Drug and device information, study documents

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