Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorders

A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorders

Determine if riluzole shows evidence of efficacy, safety, and tolerability targeting drug-refractory irritability (DRI) in persons with autism spectrum disorders (ASD).

Study Overview

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

Detailed Description

A randomized, double blind, placebo-controlled, 12-week cross-over study (5-week treatment periods with 2-week washout) of adjunctive riluzole in 12 persons with ASD and DRI between the ages of 12 and 25 years.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 12 and < 26 years.
• Weight greater than 50 kg.
• Diagnosis of ASD
• Drug-refractory irritability, as defined as screening ABC Irritability subscale (ABC-I) score of ≥18 AND 1) failure of clinically adequate treatment trials of both aripiprazole and risperidone or 2) failure of at least three previous clinically adequate drug trials targeting irritability (one trial must include aripiprazole or risperidone), as confirmed by caregiver reports and medical record review when available.
• Stable dosing of all concomitant psychotropic medications (including those targeting irritability) for four weeks prior to screening visit and during the study.
• Presence of parent/guardian willing to serve as informant for behavioral outcome measures and shipping control sample for Extracellular Signal-Related Kinase biomarker (ERK) assay.

Exclusion Criteria:

• Current use of more than two concomitant psychotropic drugs targeting irritability.
• Current use of valproic acid.
• Current use of drugs with known interaction with riluzole
• Current use of drugs with concomitant glutamatergic or glutamatergic- modulating action medications.
• For female subjects of child bearing potential, a positive serum pregnancy test.
• History of pancreatitis.
• Hemoglobin less than or equal to 8.0 gm/dL.
• Neutropenia with absolute neutrophil count less than or equal to 1.0 K/mcL.
• Problems with kidney functioning, as assessed by lab work
• Any major chronic medical or chronic respiratory illness considered to be uncontrolled by the Principal Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Riluzole; The maximum dose of riluzole to be used in this study is 200 mg per day divided BID	Drug: Riluzole; Other Names: Other name: Rilutek
Placebo Comparator: Placebo; Placebo will be administered in the same manner as the riluzole group, in order to maintain subject assignment throughout the study.	Other: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression-Improvement	A clinician-rated global assessment of symptom change rated on a scale from 1 to 7	Change from baseline to end of week 12
Aberrant Behavior Checklist- Irritability	A parent questionnaire measuring five behavioral domains	Change between baseline and end of each phase

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Logan Wink, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

General Publications

• Wink LK, Adams R, Horn PS, Tessier CR, Bantel AP, Hong M, Shaffer RC, Pedapati EV, Erickson CA. A Randomized Placebo-Controlled Cross-Over Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorder. J Autism Dev Disord. 2018 Sep;48(9):3051-3060. doi: 10.1007/s10803-018-3562-5.

Helpful Links

• Journal of Autism and Developmental Disorders (2018) 48:3051-3060

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: August 5, 2013
• First Submitted That Met QC Criteria: March 5, 2014
• First Posted (Estimate): March 7, 2014

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: April 1, 2017

More Information

Terms related to this study

• 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: CIN001- Riluzole in Autism

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No