A Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders
|Autistic Disorder Asperger Syndrome Child Development Disorders, Pervasive||Drug: N-acetylcysteine Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders|
- 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.
- 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.
|Study Start Date:||March 2007|
|Study Completion Date:||November 2009|
|Primary Completion Date:||August 2009 (Final data collection date for primary outcome measure)|
Target dose for n-acetylcysteine is 60 mg/kg/day. Capsules available in 300 mg and 600 mg strengths.
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.
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.
Subjects randomized to placebo arm will receive placebo pill for duration of study.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00453180
|United States, Indiana|
|Riley Hospital, Riley Child and Adolescent Psychiatry Clinic|
|Indianapolis, Indiana, United States, 46020|
|Principal Investigator:||Martin H. Plawecki, M.D.||Indiana University School of Medicine|