A Pilot Study of Riluzole Versus Placebo in the Treatment of Children and Adolescents With ASD (RILISE)

A Pilot Study of Riluzole vs. Placebo in the Treatment of Children and Adolescents With Autism Spectrum Disorders

This study will examine the potential efficacy and safety of riluzole for core and associated symptom domains of autism and will explore biological markers of safety and treatment response.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorders
• Intervention / Treatment: Drug: Riluzole; Drug: Placebo

Detailed Description

There are no pharmacologic treatments available for social function deficits in individuals with Autism Spectrum Disorders (ASD). The data for pharmacologic treatment of repetitive behaviors in this disorder has also become difficult to interpret given that the last two large multisite trials of selective serotonin reuptake inhibitors (SSRIs) in autism are reported to be negative for the treatment of repetitive behaviors. Only the associated symptom of irritability has 2 drugs with FDA indications whereas no systematic data exists on the pharmacologic treatment of anxiety in ASD, and response to rates to stimulants for hyperactivity are lower than what is seen in attention deficit hyperactivity disorder (ADHD). In addition, there are no biological markers of treatment response identified in this population at this point. This study will examine the potential efficacy and safety of riluzole for core and associated symptom domains of autism and will explore biological markers of safety and treatment response.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • Offord Centre for Child Studies
    • London, Ontario, Canada, N6A 5W9
      • Lawson Health Research Institute
    • Toronto, Ontario, Canada, M4G 1R8
      • Holland Bloorview Kids Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female outpatients 6-17 years of age inclusive, with a mental age equivalent ≥ 18 months at Screening visit.
2. Meet Diagnostic and Statistical Manual (DSM-IV) criteria for an ASD.
3. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Screening.

4. If already receiving stable interventions must meet the following criteria:

   1. If already receiving stable concomitant medications affecting behavior, must be on a stable dose during the preceding 1 month prior to Screening (with the exception of fluoxetine, where a period of 6 weeks is needed), and will not electively initiate new or modify ongoing medications for study duration.
   2. If already receiving stable non-pharmacological educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening, and not electively initiate new or modify ongoing interventions for the duration of the study.
5. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.
6. Ability to complete assessments- fluency in English (parent; patient, if verbal).
7. Consent to participate in the Province of Ontario Neurodevelopmental (POND) study and commitment to completing as many stages as possible of the phenotyping measures (Stages 1, 2 and 3), genomics component, and interest in being imaged through POND.
8. Ability to obtain written informed consent from the participant, if developmentally appropriate. If a participant does not have the capacity to consent, ability to obtain assent (if developmentally appropriate), as well as written informed consent from their parent(s)/legal guardian.

Exclusion Criteria:

1. Pregnant female patients; sexually active female patients on inadequate birth control.
2. Patients with a serious medical condition that, based on Investigator judgment, might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common pediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.).
3. Patients with unstable epilepsy (i.e. seizures occurring within the last 6 months), or patients with epilepsy who are not on stable doses of antiepileptic medications (i.e. dose changes within the last 3 months).
4. Patients with hypersensitivity to riluzole or any components of its formulation.
5. Patients with one or more of the following: HIV, Hepatitis B virus, Hepatitis C virus, hemophilia (bleeding problems, recent nose and brain injuries), abnormal blood pressure (hypotension or hypertension), drug abuse, immunity disorder, major depressive episode or psychosis.
6. Patients unable to tolerate venipuncture procedures for blood sampling.
7. Patients receiving concomitant medications that specifically target the glutamate system (e.g. memantine, d-cycloserine), or decrease the elimination of riluzole (e.g. theophylline, quinolones), less than 30 days prior to the screening visit.
8. Patients actively enrolled in another intervention study.
9. Patients who are unable to swallow pills.
10. Patients who have elevated liver enzymes ≥ 3 times the normal amount before the study begins.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo comparator once daily (QD) for 12 weeks for participants 6-11 years old; Placebo comparator twice daily (BID) for 12 weeks for participants 12-17 years old
Active Comparator: Riluzole	Drug: Riluzole; 50mg once daily (QD) for 12 weeks for participants 6-11 years old; 50mg twice daily (BID) for 12 weeks for participants 12-17 years old; Other Names: Rilutek

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of riluzole vs. placebo on measures of social function	This will be measured by the Aberrant Behavior Checklist (ABC) - Lethargy / Social Withdrawal Subscale	12 weeks
Efficacy of riluzole vs. placebo on measures of repetitive behaviors	This will be measured by the Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS)	12 weeks
Efficacy of riluzole vs. placebo on measures of repetitive behaviors	This will be measured by the Repetitive Behavior Scale (RBS-R)	12 weeks
Safety and tolerability of riluzole in children and adolescents with ASD	This will be measured by the Safety Monitoring Uniform Report Form (SMURF)	12 Weeks
Safety and tolerability of riluzole in children and adolescents with ASD	This will be measured by the Clinical Global Impressions - Improvement Scale - Global (CGI-I-Global)	12 Weeks

Collaborators and Investigators

• Sponsor: Evdokia Anagnostou
• Collaborators: The Hospital for Sick Children; McMaster University; Unity Health Toronto; University of Toronto; University of Western Ontario, Canada; Holland Bloorview Kids Rehabilitation Hospital
• Investigators: Principal Investigator: Evdokia Anagnostou, M.D., Holland Bloorview Kids Rehabilitation Hospital; Principal Investigator: Robert Nicolson, M.D., University of Western Ontario, Lawson Health Research Institute; Principal Investigator: Terry Bennett, M.D., McMaster University; Offord Centre for Child Studies

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: July 26, 2012
• First Submitted That Met QC Criteria: August 9, 2012
• First Posted (Estimate): August 10, 2012

Study Record Updates

• Last Update Posted (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: March 17, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Autism Spectrum Disorders
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; 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: RILISE-07-2013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No