Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00453180
Recruitment Status : Completed
First Posted : March 28, 2007
Results First Posted : June 14, 2017
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
National Alliance for Autism Research
Information provided by (Responsible Party):
Indiana University ( Indiana University School of Medicine )

Tracking Information
First Submitted Date  ICMJE March 27, 2007
First Posted Date  ICMJE March 28, 2007
Results First Submitted Date  ICMJE March 29, 2017
Results First Posted Date  ICMJE June 14, 2017
Last Update Posted Date June 14, 2017
Study Start Date  ICMJE March 2007
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 19, 2017)
  • Clinical Global Impression - Severity [ Time Frame: Week 12 ]
    The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
  • Clinical Global Impression - Improvement [ Time Frame: Week 12 ]
    Clinical Global Impression - Improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7 (1=very much improved; 2=much improved, 3=minimally Improved, 4=no change, 5=minimally worse, 6= much worse and 7=very much worse). Participants with a CGI-I score of 1 or 2 were classified as improved. Participants with a CGI score of 3, 4 or 5 were classified as no response. No participants scored 6 or 7.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2017)
  • Aberrant Behavior Checklist [ Time Frame: Week 12 ]
    The Aberrant Behavior Checklist (ABC) is a 58-item measure of maladaptive behaviors and is used as a measure of drug effects. Each of the 58 items are rated from 0 (not at all) to 3 (severe).The ABC has 5 subscales: Irritability (15 items) ranging from 0 (not at all) to 45 (severe), Lethargy (16 items) ranging from 0 (not at all) to 48 (severe), Stereotypy (7 items) ranging from 0 (not at all) to 21 (severe), Hyperactivity (16 items) ranging from 0 (not at all) to 48 (severe), and Inappropriate Speech (4 items) ranging from 0 (not at all) to 12 (severe). Higher scores indicate a higher level of maladaptive behavior.
  • Social Responsiveness Scale [ Time Frame: Week 12 ]
    The Social Responsiveness Scale (SRS) is a 65-item scale that assesses social impairment in the aspects of social awareness, social cognition, social communication, social motivation and autistic mannerisms. Each item is scored from 0 (not true) to 3 (almost always true). The total SRS raw score may range from 0-195, where higher scores indicate greater severity.
  • Pervasive Developmental Disorder Behavior Index [ Time Frame: Week 12 ]
    The PDD Behavior Inventory (PDDBI) is a rating scale filled out by caregivers or teachers that was designed to assess children having a Pervasive Developmental Disorder (PDD; autism, Asperger disorder, PDD-NOS, or childhood disintegrative disorder). Both adaptive and maladaptive behaviors are assessed in the scale, making it useful for treatment studies in which decreases in maladaptive behaviors and improvements in adaptive social and language skills relevant to PDD are expected.
  • Vineland Adaptive Behavior Scales-II (VABS-II) [ Time Frame: Week 12 ]
    The VABS-II is a semi-structured interview designed to assess adaptive functioning in the domains of communication, daily living skills and socialization. Items in each domain are rated as either 0 (does not), 1(sometimes) or 2(independently) performs a given behavior or skill. The communication domain has 99 items with scores ranging from 0-198. The daily living skills domain has 109 items with scores ranging from 0-218. The socialization domain has 99 items with scores ranging from 0-198. The domains scores are combined to form the adaptive composite score (ranging from 20-160). The raw scores from the communication, daily living skills and socialization domains along with the composite score were selected for use in this study. Higher scores indicate a higher level of adaptive functioning.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders
Official Title  ICMJE A Pilot Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders
Brief Summary The purpose of this study is to determine whether treatment with oral N-acetylcysteine (NAC) will improve behavior problems often associated with autism spectrum disorders.
Detailed Description

Autism is increasingly being recognized as a common disorder with enormous public health significance. The core symptoms of autism include severe deficits in social relatedness and communication, and interfering repetitive behavior. No medications have been shown to consistently improve any of these symptoms.

The central hypothesis of this study is that NAC will improve behavioral manifestations of autism which may include core or associated symptoms. We plan to test our hypothesis and complete the objectives of this project by pursuing the following specific aims:

  • Evaluate the efficacy of oral NAC in a 12-week, double-blind, placebo-controlled study involving 32 children and adolescents with autism spectrum disorders.
  • Evaluate the safety and tolerability of oral NAC in 32 children and adolescents with autism spectrum disorders.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Autistic Disorder
  • Asperger Syndrome
  • Child Development Disorders, Pervasive
Intervention  ICMJE
  • Drug: N-acetylcysteine
    Capsules available in 300 mg or 600mg strength. Target dose of n-acetylcysteine will be 60mg/kg/day TID. Dosage will be increased to this target dose from week 1 to week 3 barring side effects. Dose reduction will be allowed at any time for adverse side effects. Maximum dose of n-acetylcysteine will be 4200mg/day.
  • Drug: Placebo
    Subjects randomized to placebo arm will receive placebo pill for duration of study.
Study Arms  ICMJE
  • Experimental: 1
    Target dose for n-acetylcysteine is 60 mg/kg/day. Capsules available in 300 mg and 600 mg strengths.
    Intervention: Drug: N-acetylcysteine
  • Placebo Comparator: 2
    Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients.
    Intervention: Drug: Placebo
Publications * Wink LK, Adams R, Wang Z, Klaunig JE, Plawecki MH, Posey DJ, McDougle CJ, Erickson CA. A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. Mol Autism. 2016 Apr 21;7:26. doi: 10.1186/s13229-016-0088-6. eCollection 2016.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 19, 2017)
31
Original Enrollment  ICMJE
 (submitted: March 27, 2007)
32
Actual Study Completion Date  ICMJE November 2009
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 4 to 12 years.
  • Diagnosis of autistic disorder, Asperger's disorder, or PDD NOS.
  • If taking concomitant psychotropic medications, the medication must be at a constant dose for 60 days with no dose changes planned for the duration of the trial.
  • Able to swallow capsules.

Exclusion Criteria:

  • Presence of any medical condition that significantly increases risk or hampers assessment (e.g., unstable hypertension or cardiac disease, unstable asthma, kidney disease, unstable seizure disorder, pregnancy or any other medical condition as determined by the investigator).
  • Weight < 15 kg.
  • Subjects taking concomitant medications or supplements known for their glutamatergic effects (e.g., dextromethorphan, D-cycloserine, amantadine, memantine, lamotrigine, riluzole) or antioxidant properties (high dose vitamin supplements, DMG, TMG, many alternative treatments) within 30 days of the baseline visit with the exception of short term use of dextromethorphan as needed as a cough suppressant. The use of this medicine must be stopped at least 7 days prior to the baseline visit. Regular multivitamins will be allowed.
  • Subjects taking daily acetaminophen or nonsteroidal anti-inflammatory drugs within 30 days of the baseline visit.
  • Profound mental retardation as evidenced by a mental age below 18 months.
  • Subjects taking concomitant medications with the potential for pharmacokinetic or pharmacodynamic drug-drug interactions (e.g., carbamazepine) within 30 days of the baseline visit.
  • Subjects who are likely to experience significant changes in their ongoing psychosocial or medical treatments for autism over the course of the trial (e.g., initiation of new behavioral therapy, initiation of new medication or alternative treatment [e.g., chelation]). Minor changes in ongoing treatment (e.g., missed therapy sessions due to holiday/vacation; planned break in therapy due to school holidays) will not be considered significant.
  • History of prior treatment with NAC.
  • Evidence of hypersensitivity/allergy to NAC.
  • Presence of certain neurodevelopmental disorders such as Fragile X Syndrome, Tuberous Sclerosis, or other neurological disorders known to be associated with autism or autistic features.
  • Diagnosis of Rett's disorder, childhood disintegrative disorder, schizophrenia, bipolar disorder, another psychotic disorder, or substance abuse disorder.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 12 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00453180
Other Study ID Numbers  ICMJE 0611-10
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Indiana University ( Indiana University School of Medicine )
Study Sponsor  ICMJE Indiana University School of Medicine
Collaborators  ICMJE National Alliance for Autism Research
Investigators  ICMJE
Principal Investigator: Martin H. Plawecki, M.D. Indiana University School of Medicine
PRS Account Indiana University
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP