Riluzole in Fragile X Syndrome

Riluzole in Fragile X Syndrome: A Pilot Study Incorporating Biomarker Assay

The purpose of this study is to investigate the effectiveness and tolerability of riluzole in adults with Fragile X Syndrome.

Study Overview

• Status: Completed
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: Riluzole

Detailed Description

Fragile X Syndrome (FXS) represents the most common inherited form of intellectual disability. FXS is more common in males and the symptoms associated with the disorder are more marked in males. FXS is associated with characteristic physical features, behaviors, and comorbidities. Those with FXS often suffer from behavioral difficulties that include anxiety-related symptoms (shyness, social phobia, obsessive-compulsive disorder (OCD) symptoms), attention deficit hyperactivity symptoms (overarousal, hyperactivity, distractibility, impulsivity) and aggressive/self-injurious behaviors.

Riluzole is approved by the FDA for use in treating amyotrophic lateral sclerosis (ALS) in adults. Recently, riluzole has been the subject of several open-label studies describing the use of the drug in treatment-resistant depression and OCD.

Given the overlap between repetitive behavior in FXS and symptoms of OCD, it is logical to study riluzole in FXS given the compound's promise in ameliorating treatment-refractory symptoms of OCD.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Child and Adolescent Psychiatry Clinic - Riley Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females age 18 years or older.
• Confirmed molecular diagnosis of Fragile X Syndrome.
• Clinical Global Impression Severity (CGI-S) score of 3 or greater.
• Significant interfering repetitive behavior as determined by the principal investigator.
• Must be in good health as determined by screening procedures including a detailed medical history, and complete physical and neurological examination.
• Dosing of concomitant medications during the study must remain stable.

Exclusion Criteria:

• Pregnancy.
• Concomitant use of another glutamatergic agent (memantine, topiramate, amantadine, among others.
• Evidence of prior trial of riluzole and/or hypersensitivity/allergic reaction to riluzole.
• Abnormal baseline liver function tests at screen or by history; or complete blood count abnormalities at screen or by history.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Riluzole; Six week open-label treatment with riluzole, maximum dose of 50 mg twice a day.	Drug: Riluzole; Six week open-label treatment with riluzole, maximum dose of 50 mg twice a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression-Improvement (CGI-I)	The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse	Obtained at Week 6
Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)	The CY-BOCS PDD has been utilized in a largescale clinical treatment study of repetitive behavior in idiopathic ASDs. CYBOCS-PDD scores range from 0 to 20 and measure repetitive/compulsive behavior and not obsessions. Higher score indicate worse outcome.	Obtained at Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aberrant Behavior Checklist	The Aberrant Behavior Checklist (ABC) is a 58-item measure of maladaptive behaviors and is used as a measure of drug effects. The ABC has 5 subscales: Social Withdrawal (16 items) ranging from 0 (not at all) to 48 (severe), Irritability (15 items) ranging from 0 (not at all) to 45 (severe), Inappropriate Speech (4 items) ranging from 0 (not at all) to 12 (severe), Hyperactivity (16 items) ranging from 0 (not at all) to 48 (severe), and Stereotypy (7 items) ranging from 0 (not at all) to 21 (severe). Items are rated from 0 (not at all) to 3 (severe).	Week 6
The ADHD Rating Scale	The ADHD Rating Scale is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder. The ADHD Rating Scale-IV is completed by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. The total score can range from 0 to 54, with a higher score indicating greater severity	Week 6
The Clinical Global Impression - Severity Scale	The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill	Week 6
The Peabody Picture Vocabulary Test	The Peabody Picture Vocabulary Test is one of the most commonly used assessment tests that measure verbal ability in standard American English vocabulary. This test has been nationally standardized using examinees from various age groups, from children to adults. Thus, the raw scores are equated to mental age, using the norms obtained from standardization. The total standard scores range from 40 (worse receptive vocabulary) to 160 (better receptive vocabulary). The scores can also be converted to percentile rank.	Week 6
The Social Reciprocity Scale	The 65-item SRS is a standardized measure of the core symptoms of autism. Each item is scored on a 4-point Likert scale. The score of each individual item is summed to create a total raw score. A total scores results are as follows: 0-62: Within normal limits 63-79: Mild range of impairment 80-108: Moderate range of impairment 109-149: Severe range of impairment.	Week 6
Extra-cellular Signal-relatedness Kinase (ERK)	ERK activations times, as defined as the time in minutes for ERK phosphorylation to reach the half maximal level.	Screen and Week 6

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: Indiana Clinical and Translational Sciences Institute
• Investigators: Principal Investigator: Craig A. Erickson, MD, Indiana University School of Medicine

Publications and helpful links

General Publications

• Erickson CA, Weng N, Weiler IJ, Greenough WT, Stigler KA, Wink LK, McDougle CJ. Open-label riluzole in fragile X syndrome. Brain Res. 2011 Mar 22;1380:264-70. doi: 10.1016/j.brainres.2010.10.108. Epub 2010 Nov 5.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: May 6, 2009
• First Submitted That Met QC Criteria: May 6, 2009
• First Posted (Estimate): May 8, 2009

Study Record Updates

• Last Update Posted (Actual): April 18, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Fragile X Syndrome; 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: 0809-11