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

NCT00453180 | Completed Phase 2 Results DMC

• 1 other identifier: 0611-10
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Autistic Disorder; Asperger Syndrome; Child Development Disorders, Pervasive

Keywords

Autistic Disorder; Asperger's; PDD NOS; Pervasive Developmental Disorder; Autism; N-acetylcysteine; acetylcysteine; NAC; antioxidant; treatment; core symptoms; Autism Spectrum Disorders; Asperger's Disorder; Pervasive Developmental Disorder Not Otherwise Specified; Pervasive Developmental Disorders

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• Aberrant Behavior Checklist

  Week 12

• Social Responsiveness Scale

  Week 12

• Pervasive Developmental Disorder Behavior Index

  Week 12

• Vineland Adaptive Behavior Scales-II (VABS-II)

  Week 12

Study Arms (2)

1

EXPERIMENTAL

Target dose for n-acetylcysteine is 60 mg/kg/day. Capsules available in 300 mg and 600 mg strengths.

Drug: N-acetylcysteine

2

PLACEBO COMPARATOR

Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients.

Drug: Placebo

Interventions

N-acetylcysteine DRUG

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.

1

Placebo DRUG

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

2

Eligibility Criteria

• Age: 4 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indiana University School of Medicine: lead
• National Alliance for Autism Research: collaborator

Study Sites (1)

Riley Hospital, Riley Child and Adolescent Psychiatry Clinic

Indianapolis, Indiana, 46020, United States

Location

Related Publications (2)

• 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.

  PMID: 27103982 BACKGROUND

• Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

  PMID: 37811711 DERIVED

MeSH Terms

Conditions

Autistic Disorder; Asperger Syndrome; Child Development Disorders, Pervasive; Autism Spectrum Disorder

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Craig Erickson
• Organization: Cincinnati Childrens Hospital

craig.erickson@cchmc.org

513-636-6258

Study Officials

• Martin H. Plawecki, M.D.

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2007
• First Posted: March 28, 2007
• Study Start: March 1, 2007
• Primary Completion: August 1, 2009
• Study Completion: November 1, 2009
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Locations

US (1)