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

NCT00251303 | Completed Phase 2 Results

• 2 other identifiers: 05022505-M-0225
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Obsessive-Compulsive Disorder; Autism Spectrum Disorder; Autism; Asperger Disorder; Developmental Disorder

Keywords

Clinical Trial; Glutamate Antagonist; Pediatrics; Basal Ganglia; Neuropsychological; Obsessive Compulsive Disorder; OCD; Riluzole; Rilutek

Outcome Measures

Primary Outcomes (2)

• Much/Very Much Improved on Clinical Global Impressions - Improvement Score (CGI-I)

  12 weeks

• 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

Study Arms (2)

riluzole

EXPERIMENTAL

Active drug put into 10-mg capsule form,,prepared by Clinical Center Pharmacy. Dose up to 120 mg daily, divided. Brand name Rilutek.

Drug: Riluzole

placebo

PLACEBO COMPARATOR

Placebo Capsules designed to mimic active drug capsules

Drug: Placebo

Interventions

Riluzole DRUG

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.

Also known as: Rilutek

riluzole

Placebo DRUG

Capsules matched active drug in appearance.

placebo

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (12)

• 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. doi: 10.1097/01.jcp.0000245567.29531.d6. No abstract available.

  PMID: 17110840 BACKGROUND

• 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. doi: 10.1016/j.biopsych.2004.11.023.

  PMID: 15705360 BACKGROUND

• 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. doi: 10.1056/NEJM199403033300901.

  PMID: 8302340 BACKGROUND

• 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. doi: 10.1007/s00213-003-1396-z. Epub 2003 Mar 26. No abstract available.

  PMID: 12658528 BACKGROUND

• 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. doi: 10.1016/s0006-8993(00)02646-9.

  PMID: 10980239 BACKGROUND

• 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. doi: 10.1097/00004583-199806000-00017.

  PMID: 9628087 BACKGROUND

• 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. doi: 10.1097/00004583-200009000-00008.

  PMID: 10986805 BACKGROUND

• 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. doi: 10.1016/j.biopsych.2005.04.043.

  PMID: 15993857 BACKGROUND

• Russman BS, Iannaccone ST, Samaha FJ. A phase 1 trial of riluzole in spinal muscular atrophy. Arch Neurol. 2003 Nov;60(11):1601-3. doi: 10.1001/archneur.60.11.1601.

  PMID: 14623733 BACKGROUND

• 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. doi: 10.1176/appi.ajp.161.1.171.

  PMID: 14702270 BACKGROUND

• 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.

  PMID: 24356715 RESULT

• 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.

  PMID: 18315448 DERIVED

MeSH Terms

Conditions

Obsessive-Compulsive Disorder; Autism Spectrum Disorder; Autistic Disorder; Asperger Syndrome; Developmental Disabilities

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders; Child Development Disorders, Pervasive; Neurodevelopmental Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Only treatment-refractory subjects were eligible for study participation. This may have decreased treatment response. Further, 98% were taking psychotropic drugs at baseline, which may have reduced between-group differences.

Results Point of Contact

• Title: Dr. Susan E. Swedo
• Organization: National Institute of Mental Health, Pediatrics and Developmental Neuroscience Branch

swedos@mail.nih.gov

301-496-5323

Study Officials

• Susan E Swedo, MD

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Pediatrics and Developmental Neuroscience Branch

Study Record Dates

• First Submitted: November 9, 2005
• First Posted: November 9, 2005
• Study Start: August 1, 2005
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: July 15, 2014
• Results First Posted: July 15, 2014

Record last verified: 2014-07

Locations

US (1)