A Study of N-Acetyl Cysteine in Children With Autism

• ClinicalTrials.gov Identifier: NCT00627705
• Recruitment Status: Completed
• First Posted: March 3, 2008
• Results First Posted: May 18, 2017
• Last Update Posted: May 18, 2017
• Sponsor: Stanford University
• Information provided by (Responsible Party): Antonio Hardan, Stanford University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Autistic Disorder	Drug: N-Acetyl Cysteine; Other: Placebo - sugar pill	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-blind , Randomized, Placebo Controlled Study of N-Acetyl Cysteine in Autism.
• Study Start Date: February 2008
• Actual Primary Completion Date: September 2010
• Actual Study Completion Date: September 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: N-Acetyl Cysteine; active compound N-Acetyl Cysteine	Drug: N-Acetyl Cysteine; 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).; Other Name: NAC
Placebo Comparator: Sugar pill; Placebo or sugar pill	Other: Placebo - sugar pill; 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).; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Total Number of Subjects With Reported Side Effects as Assessed by Dosage Record and Treatment Emergent Symptom Scale (DOTES) [ Time Frame: 4, 8, and 12 weeks ]
   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.
2. The Clinical Global Rating Scale (CGRS) Improvement Subscale Score [ Time Frame: 12 weeks ]
   Score range 1-7 (lower score mean more improvement compared to baseline)
3. Glutathione (GSH) Levels in Peripheral Blood, Measured by State-of-the-art High-performance Liquid Chromatography (HPLC) [ Time Frame: 12 weeks ]
   Data not collected. The laboratory was not able to measure Glutathione levels.
4. Irritability Subscale of the Aberrant Behavior Checklist (ABC) [ Time Frame: baseline and 12 weeks ]
   Aberrant Behavior Checklist (ABC) Irritability Subscale Score (range 0-45); higher scores mean higher irritability

Secondary Outcome Measures :

1. The Aberrant Behavior Checklist Total Score (ABC) [ Time Frame: 4, 8, and 12 weeks ]
   Total score was not analyzed since we analyzed the sub scales. Additionally, the authors of the instrument do not recommend analyzing the total score.
2. Social Responsiveness Scale (SRS) [ Time Frame: 12 weeks ]
   SRS total score (range 0-195); higher scores mean more social impairment
3. Sensory Profile Questionnaire (SPQ) [ Time Frame: 12 weeks ]
4. Glutathione (GSH) Metabolism Intermediates in Peripheral Blood [ Time Frame: 12 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

1. DSM-IV-TR diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified
2. Prior adequate trial of N-Acetyl Cysteine
3. Active medical problems: unstable seizures, significant physical illness (e.g., serious liver or renal pathology)
4. Pregnancy or sexually active females
5. 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

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Antonio Hardan, MD; Stanford University

More Information

Publications of Results:

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.

• Responsible Party: Antonio Hardan, Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT00627705
• Other Study ID Numbers: SU-02012008-995; 10142
• First Posted: March 3, 2008
• Results First Posted: May 18, 2017
• Last Update Posted: May 18, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Additional relevant MeSH terms:

Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Acetylcysteine; N-monoacetylcystine; Antiviral Agents; Anti-Infective Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Antidotes