A Study of N-Acetyl Cysteine in Children With Autism

NCT00627705 | Completed Phase 2 Results DMC

• 2 other identifiers: SU-02012008-99510142
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to test the tolerability and efficacy of N-Acetyl Cysteine (NAC) in children with Autism. NAC is a compound that increases the levels of Glutathione, the body's main antioxidant. Glutathione is a compound in the blood that is part of a natural defense system (the antioxidant system). Anti-oxidants protect the body from damage caused by internal toxins called "free radicals." It is possible that children with Autism tend to have lower levels of glutathione, an important compound in our bodies that helps combat the effects of toxic free radicals. We hope that by studying the antioxidant system in more detail, we will increase our understanding of the reasons why people develop Autism so that we can design better ways to treat individuals with this condition. This study is meant to test the safety tolerability of NAC and its effectiveness in the treatment of behavioral difficulties in children with autism. It will also examine the possible benefit of this agent in improving the core deficits in autism such as social deficits.

Conditions

Autistic Disorder

Outcome Measures

Primary Outcomes (4)

• Total Number of Subjects With Reported Side Effects as Assessed by Dosage Record and Treatment Emergent Symptom Scale (DOTES)

  The Dosage Record and Treatment Emergent Symptom Scale (DOTES) provides information on the presence, frequency, and severity of side effects reported during the course of the trial.

  4, 8, and 12 weeks

• The Clinical Global Rating Scale (CGRS) Improvement Subscale Score

  Score range 1-7 (lower score mean more improvement compared to baseline)

  12 weeks

• Glutathione (GSH) Levels in Peripheral Blood, Measured by State-of-the-art High-performance Liquid Chromatography (HPLC)

  Data not collected. The laboratory was not able to measure Glutathione levels.

  12 weeks

• Irritability Subscale of the Aberrant Behavior Checklist (ABC)

  Aberrant Behavior Checklist (ABC) Irritability Subscale Score (range 0-45); higher scores mean higher irritability

  baseline and 12 weeks

Secondary Outcomes (4)

• The Aberrant Behavior Checklist Total Score (ABC)

  4, 8, and 12 weeks

• Social Responsiveness Scale (SRS)

  12 weeks

• Sensory Profile Questionnaire (SPQ)

  12 weeks

• Glutathione (GSH) Metabolism Intermediates in Peripheral Blood

  12 weeks

Study Arms (2)

N-Acetyl Cysteine

ACTIVE COMPARATOR

active compound N-Acetyl Cysteine

Drug: N-Acetyl Cysteine

Sugar pill

PLACEBO COMPARATOR

Placebo or sugar pill

Other: Placebo - sugar pill

Interventions

N-Acetyl Cysteine DRUG

Phase 1: Oral, 900 mg daily for 4 weeks Phase 2: Oral, 900 mg twice daily 4 weeks Phase 3: Oral, 900 mg three times daily for 4 weeks Entire intervention lasts for 12 weeks (drug administration is continuous).

Also known as: NAC

N-Acetyl Cysteine

Placebo - sugar pill OTHER

Phase 1: Oral, 900 mg daily for 4 weeks Phase 2: Oral, 900 mg twice daily 4 weeks Phase 3: Oral, 900 mg three times daily for 4 weeks Entire intervention lasts for 12 weeks (drug administration is continuous).

Also known as: Placebo

Sugar pill

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Outpatients between 3.0 and 12.11 years of age inclusive
• Males and females who are physically healthy
• diagnosis of autism based Diagnostic and Statistical Manual (DSM-IV-TR) criteria, the Autism Diagnostic Interview-Revised, and expert clinical evaluation
• Clinical Global Impression Severity rating of 4
• Care provider who can reliably bring subject to clinic visits, can provide trustworthy ratings, and interacts with subject on a regular basis
• Ability of subject to swallow the compound
• Stable concomitant medications for at least 2 weeks
• No planned changes in psychosocial interventions during the open-label N-Acetyl Cysteine trial

You may not qualify if:

• DSM-IV-TR diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified
• Prior adequate trial of N-Acetyl Cysteine
• Active medical problems: unstable seizures, significant physical illness (e.g., serious liver or renal pathology)
• Pregnancy or sexually active females
• Subjects taking antioxidant agents and glutathione prodrugs will be excluded from the study except if they have been off these compounds for at least 4 weeks

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, Frazier TW, Tirouvanziam R. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012 Jun 1;71(11):956-61. doi: 10.1016/j.biopsych.2012.01.014. Epub 2012 Feb 18.

  PMID: 22342106 RESULT

MeSH Terms

Conditions

Autistic Disorder

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The sample size was relatively small and the age range was narrow, which limits the generalizability of the findings. Most subjects were taking psychotropic medications and were receiving behavioral interventions.

Results Point of Contact

• Title: Antonio Hardan, MD
• Organization: Stanford University School of Medicine

hardanay@stanford.edu

650-736-1235

Study Officials

• Antonio Hardan, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 22, 2008
• First Posted: March 3, 2008
• Study Start: February 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: May 18, 2017
• Results First Posted: May 18, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)