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

Tracking Information
First Submitted Date ICMJE	November 9, 2005
First Posted Date ICMJE	November 9, 2005
Results First Submitted Date	May 16, 2013
Results First Posted Date	July 15, 2014
Last Update Posted Date	July 15, 2014
Study Start Date ICMJE	August 2005
Actual Primary Completion Date	February 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 14, 2014)	Much/Very Much Improved on Clinical Global Impressions - Improvement Score (CGI-I) [ Time Frame: 12 weeks ]; Children's Yale-Brown Obsessive-Compulsive Scale Scores (CY-BOCS) [ Time Frame: 12 weeks ]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.
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00251303 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
Official Title ICMJE	An Investigation of the Efficacy in Childhood Obsessive-Compulsive Disorder of Riluzole: An Antiglutamatergic Agent
Brief Summary	This study will examine the effectiveness of riluzole for treating Obsessive-Compulsive Disorder in Youth, Including those with Autism Spectrum Disorders.
Detailed 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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Obsessive-Compulsive Disorder; Autism Spectrum Disorder; Autism; Asperger Disorder; Developmental Disorder
Intervention ICMJE	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. Other Name: Rilutek; Drug: Placebo Capsules matched active drug in appearance.
Study Arms	Experimental: riluzole Active drug put into 10-mg capsule form,,prepared by Clinical Center Pharmacy. Dose up to 120 mg daily, divided. Brand name Rilutek. Intervention: Drug: Riluzole; Placebo Comparator: placebo Placebo Capsules designed to mimic active drug capsules Intervention: Drug: Placebo
Publications *	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.; 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.; 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.; 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.; 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.; 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.; 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.; 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.; Russman BS, Iannaccone ST, Samaha FJ. A phase 1 trial of riluzole in spinal muscular atrophy. Arch Neurol. 2003 Nov;60(11):1601-3.; 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.; 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: 10.1038/npp.2013.343. Epub 2013 Dec 19.; Grant P, Lougee L, Hirschtritt M, Swedo SE. An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2007 Dec;17(6):761-7. doi: 10.1089/cap.2007.0021.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: April 8, 2011)	78
Original Enrollment ICMJE; (submitted: November 8, 2005)	36
Actual Study Completion Date	February 2012
Actual Primary Completion Date	February 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	INCLUSION CRITERIA: Subjects may be included in the study only if they meet all of the following criteria: Male or female subjects, 7 to 17 years of age.; Male and female subjects of childbearing potential must be using a medically accepted means of contraception or must remain abstinent.; 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.; 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.; 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.; Subjects must be able to swallow capsules. EXCLUSION CRITERIA: Subjects will be excluded from the study for any of the following reasons: 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.; 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.; Disabling Tic Disorder requiring contraindicated medicines.; Male or female subjects who are unwilling to use effective contraception, or female subjects who are pregnant or nursing.; Serious unstable illnesses, including gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.; 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.; Documented history of hypersensitivity or intolerance to riluzole.; DSM-IV Substance Abuse Disorder within the past 90 days or Substance Dependence Disorder within the past 5 years, or any use of tobacco.; Taking contraindicated drugs.; Unable to swallow capsules.; In addition, patients will not receive cognitive-behavior therapy during the period of the study.; Abnormal EEG unless evaluated by a neurologist and approved by that specialist for this protocol.
Sex/Gender	Sexes Eligible for Study: All
Ages	7 Years to 17 Years (Child)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00251303
Other Study ID Numbers ICMJE	050225; 05-M-0225 ( Other Identifier: NIMH Office of Protocol Services )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Susan Swedo, M.D., National Institutes of Health Clinical Center (CC)
Study Sponsor ICMJE	National Institute of Mental Health (NIMH)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Susan E Swedo, MD National Institute of Mental Health (NIMH)
PRS Account	National Institutes of Health Clinical Center (CC)
Verification Date	July 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP