A Study of N-Acetyl Cysteine in Children With Autism

Study Overview
=================
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.

Official Title
-----------------
Double-blind , Randomized, Placebo Controlled Study of N-Acetyl Cysteine in Autism.

Conditions
-----------------
Autistic Disorder

Intervention / Treatment
-----------------
* Drug: N-Acetyl Cysteine
* Other: Placebo - sugar pill


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: N-Acetyl Cysteine<br>active compound N-Acetyl Cysteine | Drug: N-Acetyl Cysteine<br>* 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).<br>* Other names: NAC;|
| Placebo Comparator: Sugar pill<br>Placebo or sugar pill | Other: Placebo - sugar pill<br>* 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).<br>* Other names: Placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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