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

Autistic Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00453180
• Other study ID #: 0611-10
• Status: Completed
• Phase: Phase 2
• First received: March 27, 2007
• Last updated: May 19, 2017
• Start date: March 2007
• Est. completion date: November 2009

Study information

• Verified date: May 2017
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: November 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 12 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asperger Syndrome
• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive
• Developmental Disabilities
• Disease

Intervention

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.
• Placebo
Subjects randomized to placebo arm will receive placebo pill for duration of study.

Locations

Country	Name	City	State
United States	Riley Hospital, Riley Child and Adolescent Psychiatry Clinic	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University School of Medicine	National Alliance for Autism Research

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Global Impression - Severity	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.	Week 12
Primary	Clinical Global Impression - Improvement	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.	Week 12
Secondary	Aberrant Behavior Checklist	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.	Week 12
Secondary	Social Responsiveness Scale	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.	Week 12
Secondary	Pervasive Developmental Disorder Behavior Index	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.	Week 12
Secondary	Vineland Adaptive Behavior Scales-II (VABS-II)	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.	Week 12