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

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

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.

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

Conditions
-----------------
Autism Spectrum Disorders

Intervention / Treatment
-----------------
* Drug: Riluzole
* Other: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 25 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 |