Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders

Autism Spectrum Disorder Clinical Trial

Official title:

An Investigation of the Efficacy in Childhood Obsessive-Compulsive Disorder of Riluzole: An Antiglutamatergic Agent

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00251303
• Other study ID #: 050225
• Secondary ID: 05-M-0225
• Status: Completed
• Phase: Phase 2
• First received: November 9, 2005
• Last updated: July 14, 2014
• Start date: August 2005
• Est. completion date: February 2012

Study information

• Verified date: July 2014
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

This study will examine the effectiveness of riluzole for treating Obsessive-Compulsive Disorder in Youth, Including those with Autism Spectrum Disorders.

Description:

Obsessive-Compulsive Disorder (OCD) is a chronic psychiatric disorder characterized by the presence of intrusive and unwanted obsessional thoughts and images and of compulsive behaviors. Its presentation during childhood is similar to that seen in adulthood, except that children sometimes lack insight into the senselessness of the thoughts and behaviors. Although many patients benefit from treatment with selective serotonin reuptake inhibitors (SSRIs), a significant proportion have limited or no response to these medications. Cognitive behavioral therapy (CBT) may also be effective for OCD, alone or in combination with SSRIs, but there is a shortage of qualified therapists, and many patients and families cannot participate effectively in the therapy.

There is a pressing need, then, for the development of alternative, novel treatments for pediatric OCD. Neuropsychological and neuroimaging data suggest that OCD may arise from dysfunction of orbitofronto-striato-thalamocortical circuitry. Glutamate plays a crucial role in the regulation of excitatory activity within this circuit and may be involved in the etiopathogenesis of OCD. If so, then agents which reduce glutamatergic neurotransmission may provide unique antiobsessional benefits. Riluzole is a medication that reduces glutamatergic activity. A small open-label trial suggested that it might reduce OCD severity among children and adolescents.

The investigation will enroll up to 80 pediatric subjects with OCD including some who have both autistic spectrum disorder (ASD) and OCD. The subjects will participate in a double-blind, placebo-controlled 12-week trial of riluzole as a sole agent or as an augmentation to their currently inadequate therapy. Following the double-blind portion of the trial, subjects may receive three months of open-label treatment with riluzole, if it is clinically indicated. All subjects will be followed at regular intervals until one year from baseline.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Years to 17 Years

Eligibility

• INCLUSION CRITERIA:

Subjects may be included in the study only if they meet all of the following criteria:

1. Male or female subjects, 7 to 17 years of age.

2. Male and female subjects of childbearing potential must be using a medically accepted means of contraception or must remain abstinent.

3. Each legal guardian must have a level of understanding sufficient to agree to all required tests and examinations. Each legal guardian must understand the nature of the study. Each legal guardian must consent to study protocol.

4. Subjects must fulfill DSM-IV criteria for (OCD) and have a CY-BOCS score of greater than 20. In the double-blind phase, subjects enrolled in the combined OCD and ASD cohort must also meet DSM-IV criteria for Pervasive Developmental Disorder as well as OCD.

5. Each subject already taking medicine must be taking usually effective doses of a medicine demonstrated to be effective in childhood OCD, must have been stable on that dose for at least six weeks, and must have no newly recognized or intolerable adverse effects from that medicine. Subjects who are currently not taking such a medication must have had adequate trial in the past of at least one medicine that has been shown to be effective for the symptoms of childhood OCD, and must have failed to see improvement or must have had intolerable adverse effects from the medicine.

6. Subjects must be able to swallow capsules.

EXCLUSION CRITERIA:

Subjects will be excluded from the study for any of the following reasons:

1. Presence of psychotic symptoms or lifetime history of schizophrenia, bipolar disorder, other psychotic disorder, or other serious unstable psychiatric illness. Medically unstable due to binging, purging, or starvation.

2. Judged clinically to be at risk for suicide (suicidal ideation, severe depression, or other factors). Diagnosis of DSM-IV Major Depressive Disorder is not necessarily an exclusion criterion.

3. Disabling Tic Disorder requiring contraindicated medicines.

4. Male or female subjects who are unwilling to use effective contraception, or female subjects who are pregnant or nursing.

5. Serious unstable illnesses, including gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.

6. Renal or hepatic dysfunction that would interfere with excretion or metabolism of riluzole as evidenced by increase above upper limits of normal for BUN/creatinine, or more than two-fold elevation above upper limits of normal of serum transaminases (ALT/SGPT, AST/SGOT), gamma glutamate (GGT), or bilirubin.

7. Documented history of hypersensitivity or intolerance to riluzole.

8. DSM-IV Substance Abuse Disorder within the past 90 days or Substance Dependence Disorder within the past 5 years, or any use of tobacco.

9. Taking contraindicated drugs.

10. Unable to swallow capsules.

11. In addition, patients will not receive cognitive-behavior therapy during the period of the study.

12. Abnormal EEG unless evaluated by a neurologist and approved by that specialist for this protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asperger Disorder
• Asperger Syndrome
• Autism
• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive
• Compulsive Behavior
• Developmental Disabilities
• Developmental Disorder
• Disease
• Obsessive-Compulsive Disorder

Intervention

Drug:
• Riluzole
Active drug put into 10-mg capsules by NIH Clinical Center Pharmacy. Matched placebo capsules were also prepared by NIH Clinical Center Pharmacy. Dose up to 120 mg daily, divided into bid dosages.
• Placebo
Capsules matched active drug in appearance.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (11)

Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994 Mar 3;330(9):585-91. — View Citation

Coric V, Milanovic S, Wasylink S, Patel P, Malison R, Krystal JH. Beneficial effects of the antiglutamatergic agent riluzole in a patient diagnosed with obsessive-compulsive disorder and major depressive disorder. Psychopharmacology (Berl). 2003 May;167(2):219-20. Epub 2003 Mar 26. — View Citation

Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. — View Citation

Grant PJ, Joseph LA, Farmer CA, Luckenbaugh DA, Lougee LC, Zarate CA Jr, Swedo SE. 12-week, placebo-controlled trial of add-on riluzole in the treatment of childhood-onset obsessive-compulsive disorder. Neuropsychopharmacology. 2014 May;39(6):1453-9. doi: — View Citation

McGrath MJ, Campbell KM, Parks CR, Burton FH. Glutamatergic drugs exacerbate symptomatic behavior in a transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder. Brain Res. 2000 Sep 15;877(1):23-30. — View Citation

Moore GJ, MacMaster FP, Stewart C, Rosenberg DR. Case study: caudate glutamatergic changes with paroxetine therapy for pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 1998 Jun;37(6):663-7. — View Citation

Rosenberg DR, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ. Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry. 2000 Sep;39(9):1096-103. — View Citation

Russman BS, Iannaccone ST, Samaha FJ. A phase 1 trial of riluzole in spinal muscular atrophy. Arch Neurol. 2003 Nov;60(11):1601-3. — View Citation

Sasso DA, Kalanithi PS, Trueblood KV, Pittenger C, Kelmendi B, Wayslink S, Malison RT, Krystal JH, Coric V. Beneficial effects of the glutamate-modulating agent riluzole on disordered eating and pathological skin-picking behaviors. J Clin Psychopharmacol. 2006 Dec;26(6):685-7. — View Citation

Zarate CA Jr, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D, Charney DS, Manji HK. An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry. 2004 Jan;161(1):171-4. — View Citation

Zarate CA Jr, Quiroz JA, Singh JB, Denicoff KD, De Jesus G, Luckenbaugh DA, Charney DS, Manji HK. An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. Biol Psychiatry. 2005 Feb 15;57(4):430-2. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Much/Very Much Improved on Clinical Global Impressions - Improvement Score (CGI-I)		12 weeks	No
Primary	Children's Yale-Brown Obsessive-Compulsive Scale Scores (CY-BOCS)	CY-BOCS is a 0-40 point scale of obsessive-compulsive symptom severity, higher number indicates more severe obsessive-compulsive symptoms. Comparison of 12 weeks scores for placebo and riluzole groups.	12 weeks	No