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N-acetylcysteine (NAC) for Children With Tourette Syndrome

This study has been completed.
Sponsor:
Collaborator:
American Academy of Child Adolescent Psychiatry.
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01172288
First received: July 27, 2010
Last updated: December 19, 2016
Last verified: December 2016
  Purpose

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.


Condition Intervention Phase
Tourettes Syndrome
Tic
Drug: N-Acetylcysteine (NAC)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo-Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Children With Tourette Syndrome

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Improvement in Tic Severity [ Time Frame: 12 weeks ]

    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.



Secondary Outcome Measures:
  • Improvement of Premonitory Urges [ Time Frame: 12 weeks ]
    Premonitory Urge for Tics Scale (PUTS). Items are rated on a scale of 1-4 from "least" to "most." A total score is calculated by summing the scores of all items. Nine is the minimum possible score. A score of 12.5-24.5 indicates medium intensity of premonitory urges for tics. A score of 25-30.5 indicates high intensity which may be associated with marked impairment. Scores 31 and above indicate extremely high intensity with probable severe impairment. A score of 36 is the maximum score possible.

  • Improvement in OCD Severity [ Time Frame: 12 weeks ]
    Childrens' Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). 10-item scale. Each item is rated from 0-4. A sum total is calculated by adding items 1-10. 0-7: Subclinical. 8-15: Mild. 16-23: Moderate. 24-31: Severe. 32-40: Extreme.

  • Overall Improvement [ Time Frame: 12 weeks ]
    Clinical Global Impression - Improvement Scale (CGI-I). The CGI is a 7-point scare that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse.

  • Number of Participants With Adverse Effects [ Time Frame: 12 weeks ]
    Number of participants with adverse events according to the Pediatric Adverse Events Rating Scale


Enrollment: 31
Study Start Date: July 2010
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: N-Acetylcysteine
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)
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 Comparator: Placebo
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
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.

  Eligibility

Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01172288

Locations
United States, Connecticut
Yale Child Study Center
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
American Academy of Child Adolescent Psychiatry.
Investigators
Principal Investigator: Michael H. Bloch, MD, MS Yale University
  More Information

Additional Information:
Publications:

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01172288     History of Changes
Other Study ID Numbers: YCSC1004006637
Study First Received: July 27, 2010
Results First Received: June 30, 2016
Last Updated: December 19, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Yale University:
Tic disorders,
Tourette syndrome
Chronic Tic Disorders

Additional relevant MeSH terms:
Syndrome
Tourette Syndrome
Disease
Pathologic Processes
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tic Disorders
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Neurodevelopmental Disorders
Mental Disorders
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
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 April 28, 2017