Clinical trial NCT01172275: N-acetylcysteine (NAC) for Pediatric Obsessive-Compulsive Disorder
Official title: Double-Blind, Placebo-Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Pediatric Obsessive-Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obsessive-Compulsive Disorder
Keywords: Obsessive-Compulsive Disorder
OCD
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2010-07-29
Enrollment: 11
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: OCD Severity at 12 Weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Overall Improvement at 12 Weeks
timeFrame: 12 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Child Study Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Michael H. Bloch, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1007/s00213-005-0246-6. Epub 2005 Dec 22.
citation: 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. doi: 10.1001/archgenpsychiatry.2009.60.
citation: 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. doi: 10.1016/j.biopsych.2008.04.022. Epub 2008 Jun 5.
citation: 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. doi: 10.1016/j.biopsych.2008.03.004. Epub 2008 Apr 23.
citation: 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. doi: 10.1017/S1461145707008401. Epub 2008 Jan 21.