N-acetylcysteine (NAC) for Pediatric Obsessive-Compulsive Disorder - Full Text View

Purpose

Pediatric Obsessive-Compulsive Disorder (OCD) affects 1-3% of children. The investigators currently have effective first-line interventions for pediatric OCD such as Cognitive Behavioral Therapy (CBT) and pharmacotherapy with serotonin reuptake inhibitors (SRIs). However, roughly half of children with OCD still have clinically significant OCD symptoms despite treatment with first-line pharmacological treatments and CBT interventions for OCD. Furthermore, all pharmacological treatments for OCD in children have an increased side effect burden when compared to adults. Novel treatments for children with OCD are needed.

N-acetylcysteine (NAC) is a natural supplement that acts as an antioxidant and a glutamate modulating agent. NAC has been used safely for decades in doses 20-40 times higher than in this trial as an antidote for acetaminophen overdose. The only side-effect commonly seen with NAC is nausea and this side-effect is seldom seen in the doses used in this trial.

NAC has recently been demonstrated to be effective in a double-blind, placebo-controlled trial in adults with trichotillomania (chronic hair pulling). Trichotillomania is an obsessive-compulsive spectrum disorder that is hypothesized to be closely related to OCD. In other trials NAC has evidence of some efficacy in treating diverse psychiatric conditions such as bipolar depression, schizophrenia and cocaine dependence.

The investigators are conducting this trial to determine if NAC is effective in treating OCD.

Condition	Intervention	Phase
Obsessive-Compulsive Disorder	Drug: N-Acetylcysteine Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Double-Blind, Placebo-Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Pediatric Obsessive-Compulsive Disorder

Resource links provided by NLM:

MedlinePlus related topics: Obsessive-Compulsive Disorder

Drug Information available for: Acetylcysteine

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:

Improvement in OCD Severity [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS)

Secondary Outcome Measures:

Improvement in OCD Symptom Dimensions [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS)
Overall Improvement [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Clinician Global Improvement Scale (CGI)
Adverse Effects [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Pediatric Adverse Events Rating Scale (PAERS)

Estimated Enrollment:	40
Study Start Date:	July 2012
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: N-Acetylcysteine	Drug: N-Acetylcysteine 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial.
Placebo Comparator: Placebo	Drug: Placebo 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.

Eligibility

Ages Eligible for Study:	8 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Children aged 8-17 years.
Primary diagnosis of OCD.
Duration of OCD greater than 6 months.
Significant Current OCD symptoms: Current CY-BOCS score > or = 16.

Exclusion Criteria:

Comorbid bipolar disorder, psychotic disorder, substance use disorder, developmental disorder or mental retardation (IQ<70).
Recent change (less than 4 weeks) in medications that have potential effects on OCD severity (such as Selective Serotonin Reuptake Inhibitors, clomipramine, naltrexone, lithium, psychostimulants, anxiolytics, or antipsychotics). Medication change is defined to include either dose changes or medication discontinuation.
Recent change in behavioral treatment for OCD or comorbid conditions within the last 4 weeks or initiation of behavioral therapy for tics within the last 12 weeks.
Asthma requiring medication use within the last 3 months (case reports have linked intravenous NAC administration with asthma exacerbation)
Known hypersensitivity or previous anaphylactoid reaction to acetylcysteine or any components in its preparation.
Positive pregnancy test or drug screening test.
Previous use of N-acetylcysteine (dose greater than 600mg for more than 2 weeks).
Previous history or suspicion of cystinuria because of a possibility of forming kidney stones.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01172275

Contacts

Contact: Jilian Mulqueen, BA	(203) 737-4809	jilian.mulqueen@yale.edu
Contact: Michael H. Bloch, MD, MS	(203) 974-7551	michael.bloch@yale.edu

Locations

United States, Connecticut
Yale Child Study Center	Recruiting
New Haven, Connecticut, United States, 06520

Sponsors and Collaborators

Yale University

Investigators

Principal Investigator:

Michael H. Bloch, MD, MS

Yale University

More Information

Additional Information:

Yale OCD Adult Research Clinic This link exits the ClinicalTrials.gov site

Publications:

Lafleur DL, Pittenger C, Kelmendi B, Gardner T, Wasylink S, Malison RT, Sanacora G, Krystal JH, Coric V. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology (Berl). 2006 Jan;184(2):254-6. Epub 2005 Dec 22.

Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009 Jul;66(7):756-63.

Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI. N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial. Biol Psychiatry. 2008 Sep 15;64(6):468-75. Epub 2008 Jun 5.

Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008 Sep 1;64(5):361-8. Epub 2008 Apr 23.

Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008 Sep;11(6):851-76. Epub 2008 Jan 21. Review.

Responsible Party:	Michael Bloch, Assistant Professor, Yale University
ClinicalTrials.gov Identifier:	NCT01172275 History of Changes
Other Study ID Numbers:	YCSC1004006623
Study First Received:	July 27, 2010
Last Updated:	October 3, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Yale University:

Obsessive-Compulsive Disorder
OCD

Additional relevant MeSH terms:

Obsessive-Compulsive Disorder
Anxiety Disorders
Mental Disorders
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on May 16, 2013