N-acetylcysteine (NAC) for Children With Tourette Syndrome

NCT01172288 | Completed Phase 2 Results

• 1 other identifier: YCSC1004006637
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tourettes Syndrome; Tic

Keywords

Tic disorders,; Tourette syndrome; Chronic Tic Disorders

Outcome Measures

Primary Outcomes (1)

• Improvement in Tic Severity

  Yale Global Tic Severity Scale is a standard psychiatric measure that rates tics from 0 (no tics) to 100 (most severe tics). It separately rates motor tics and vocal tics in 5 subscales (number, frequency, intensity, complexity and interference) where the maximum severity score for motor tics is 25 and for vocal tics is 25. Giving us the Total Tic Severity Score maximum of 50. The additional Impairment Scale rates the degree of disability caused by the tics ranging from 0 (none) to 50 (severe). When these two scores are added we get the Yale Global Tic Severity Scale Score.

  12 weeks

Secondary Outcomes (4)

• Improvement of Premonitory Urges

  12 weeks

• Improvement in OCD Severity

  12 weeks

• Overall Improvement

  12 weeks

• Number of Participants With Adverse Effects

  12 weeks

Study Arms (2)

N-Acetylcysteine

EXPERIMENTAL

NAC was titrated up to a maximum dose of 2400 mg over the course of 2 weeks. Subjects were assigned 600 mg twice a day for weeks 1-2, and then were assigned 1200 mg twice a day for the remainder of the 12 week study.

Drug: N-Acetylcysteine (NAC)

Placebo

PLACEBO COMPARATOR

Placebo: Subjects were assigned to take two capsules twice a day for weeks 1-2, and then were assigned 4 capsules twice a day for the remainder of the 12 week study.

Drug: Placebo

Interventions

N-Acetylcysteine (NAC) DRUG

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.

N-Acetylcysteine

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Yale University: lead
• American Academy of Child Adolescent Psychiatry.: collaborator

Study Sites (1)

Yale Child Study Center

New Haven, Connecticut, 06520, United States

Location

Related Publications (7)

• 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.

  PMID: 19581567 BACKGROUND

• 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.

  PMID: 19913654 BACKGROUND

• 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.

  PMID: 18534556 BACKGROUND

• 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.

  PMID: 18436195 BACKGROUND

• 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.

  PMID: 18205981 BACKGROUND

• 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.

  PMID: 20022434 BACKGROUND

• Bloch MH, Panza KE, Yaffa A, Alvarenga PG, Jakubovski E, Mulqueen JM, Landeros-Weisenberger A, Leckman JF. N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized, Double-Blind, Placebo-Controlled Add-On Trial. J Child Adolesc Psychopharmacol. 2016 May;26(4):327-34. doi: 10.1089/cap.2015.0109. Epub 2016 Mar 30.

  PMID: 27027204 RESULT

Related Links

• Yale Child Study Center TS/OCD Clinic

MeSH Terms

Conditions

Tourette Syndrome; Tics; Tic Disorders

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Associate Professor
• Organization: Yale University- School of Medicine

michael.bloch@yale.edu

(203)737-4809

Study Officials

• Michael H. Bloch, MD, MS

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2010
• First Posted: July 29, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: February 10, 2017
• Results First Posted: December 19, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)