N-acetylcysteine (NAC) for Children With Tourette Syndrome

Tic Clinical Trial

Official title:

Double-Blind, Placebo-Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Children With Tourette Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01172288
• Other study ID #: YCSC1004006637
• Status: Completed
• Phase: Phase 2
• First received: July 27, 2010
• Last updated: July 21, 2014
• Start date: July 2010
• Est. completion date: January 2014

Study information

• Verified date: July 2014
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Tourette syndrome is a childhood-onset neuropsychiatric disorder characterized by multiple motor and vocal tics that last for at least a year in duration. Currently, there exist several effective pharmacological treatments for childhood tics including alpha-2 agonist medications (guanfacine and clonidine) and neuroleptics (antipsychotic) medications. These medications, however, have significant side-effects and are only partially efficacy in treating tics.

N-acetylcysteine (NAC) is a natural supplement that acts as an antioxidant and 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). Hairpulling is hypothesized to be closely related to tics because these conditions (1) have similar clinical characteristics -- both groups typically experience urges before engaging in pulling or tics, (2) neuroimaging studies suggest they involve similar brain circuits -- the basal ganglia, (3) the same pharmacological treatments (neuroleptics) may be effective for both conditions and (4) they tend to be inherited together in families. 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 an effective treatment for tics.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 17 Years

Eligibility

Inclusion Criteria:

• Children aged 8-17 years.

• Primary diagnosis of Tourette syndrome or chronic tic disorder.

• Duration of tics greater than 1 year.

• Significant Current tic symptoms: Current YGTSS score greater than or equal to 22 with a TS diagnosis or greater than or equal to 14 with a chronic tic disorder.

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 tic severity (such as neuroleptic medications, dopamine agonists, alpha-2 agonists (guanfacine, clonidine or prazosin), SSRIs, clomipramine, naltrexone, lithium, psychostimulants, or anxiolytics). Medication change is defined to include dose changes or medication discontinuation.

• Recent change in behavioral treatment for Tourette syndrome or comorbid conditions (i.e. OCD) 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

• 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)

Study Design

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

Related Conditions & MeSH terms

• Syndrome
• Tic
• Tourette Syndrome
• Tourettes Syndrome

Intervention

Drug:
• N-Acetylcysteine (NAC)
1 600mg capsule twice a day for 2 weeks and then 2 600mg capsules twice a day for the remaining 10 weeks of the trial.
• Placebo
1 600mg Capsule twice a day for two weeks then 2 600mg capsules twice a day for the remaining 10 weeks of the study. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.

Locations

Country	Name	City	State
United States	Yale Child Study Center	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	American Academy of Child Adolescent Psychiatry.

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View 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. — View Citation

Bloch MH, Leckman JF. Clinical course of Tourette syndrome. J Psychosom Res. 2009 Dec;67(6):497-501. doi: 10.1016/j.jpsychores.2009.09.002. Review. — View 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. — View 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. Review. — View Citation

Singer HS, Morris C, Grados M. Glutamatergic modulatory therapy for Tourette syndrome. Med Hypotheses. 2010 May;74(5):862-7. doi: 10.1016/j.mehy.2009.11.028. Epub 2009 Dec 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in Tic Severity	Yale Global Tic Severity Scale (Total Tic Score)	12 weeks	No
Secondary	Improvement of Premonitory Urges	Premonitory Urge for Tics Scale (PUTS)	12 weeks	No
Secondary	Improvement in OCD Severity	Childrens' Yale-Brown Obsessive-Compulsive Scale (CY-BOCS)	12 weeks	No
Secondary	Overall Improvement	Clinical Global Improvement Scale	12 weeks	No
Secondary	Adverse Effects	Pediatric Adverse Events Rating Scale	12 weeks	No