NAC: A Feasibility Study of N-acetylcysteine for Self-injurious Behavior in Children With Autism Spectrum Disorder

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03008889
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arms: 2
• Actual Duration (Months): 14.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate the feasibility of a 9-week, randomized trial of N-acetylcysteine (NAC) compared to placebo in 14 children (age 5 to 12 years) with Autism Spectrum Disorder (ASD) and a moderate level of repetitive self-injurious behavior (SIB). Additional aims are to evaluate the positive predictive value of a screening method to classify children with automatically maintained self-injurious behavior; to evaluate the preliminary efficacy of NAC for reducing repetitive SIB in children with ASD; and to evaluate biomarkers and possible mechanisms of action of NAC in children with ASD.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder	Drug: N-acetylcysteine; Drug: Placebo	Phase 2

Detailed Description

Self-injurious behavior (SIB) in children with autism spectrum disorder (ASD) can cause physical harm to the child and interfere with the child's ability to make use of educational programs and helpful treatments such as speech therapy. The turmoil caused by self-injurious behaviors in children with ASD invariably interferes with daily routines because family life often stops during these episodes and family members worry about setting off SIB between episodes. This project will use the detailed assessment methods developed in the field of behavior therapy to evaluate the potential for N-acetylcysteine (NAC) to treat children with ASD and moderate repetitive SIB. NAC is an over-the-counter dietary supplement that may have beneficial effects on the brain through its well-documented antioxidant effects and/or reduced glutamate signaling. In the proposed study, 14 children with ASD and repetitive SIB between the ages of 5 and 12 will be randomly assigned to gradually increasing doses of NAC or placebo for 9 weeks. The research team, parents and children will be blind to the treatment with NAC or placebo. Participants will come to the research site periodically to complete measures and behavioral assessments.

After the 9 weeks of treatment, children randomized to NAC who showed improvement will be encouraged to continue taking the supplement outside the study. Children who were randomly assigned to the placebo and showed no improvement will be offered open-label treatment with NAC. Children who did not improve while taking NAC or those who improved while on the placebo will be advised on next steps by the study team.

The goal of this feasibility study is establish the acceptability viability of study procedures in this vulnerable population, to learn about the potential benefits and adverse effects of NAC. Demonstrating these feasibility aims and the preliminary efficacy and safety of NAC is a prerequisite for planning a larger, more definitive, study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Feasibility Study of N-acetylcysteine for Self-injurious Behavior in Children With Autism Spectrum Disorder
• Actual Study Start Date: Jul 5, 2018
• Actual Primary Completion Date: Sep 12, 2019
• Actual Study Completion Date: Sep 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants taking NAC Participants randomized to the active treatment study arm will receive gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that will be used a higher than usual doses in this study.	Drug: N-acetylcysteine; Participants will start with taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28. If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.; Other Names: NAC
Placebo Comparator: Participants taking Placebo Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients.	Drug: Placebo; Participants will start with taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. The dosing for the placebo will increase in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28. If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Randomized [12 months (throughout the duration of the study)]

   Goal: randomize 1.75 participants per month

2. Attrition Rate [12 months (throughout the duration of the study)]

   Attrition rate is defined as the percent of subjects who did not complete the study. Goal:less than 15% (to indicate that study was acceptable to participants and parents).

3. Study Medication Compliance [12 months (throughout the duration of the study)]

   Goal: at least 70% treatment compliance (tablet counts and drug dairies).

4. Successful Collection of Outcome Measures [12 months (throughout the duration of the study)]

   Goal: at least 80% collection of essential outcome data to demonstrate the feasibility of data collection procedures.

5. Parent Satisfaction Rating [Week 9 (at the end of the study intervention)]

   Goal: at least 80% of parents will agree or strongly agree when asked in an anonymous survey that they would recommend the study and the study treatment to other parents of children with ASD and SIB.

Secondary Outcome Measures

1. Positive Predictive Value of Screening Method of Classifying Self-injurious Behavior (SIB) by Type. [12 months (duration of the study)]

   Goal: at least 75% positive predictive value of our screening method to classify children with automatically maintained self-injurious behavior using a semi-structured interview at screening compared to the findings of five- to six-hour functional analysis at baseline. Only children who appear to have automatically maintained SIB will be referred for the baseline evaluation. Demonstrating a high positive predictive value for the screening method is a necessary prerequisite for launching a larger study. Using the formula: Positive Predictive Value (PPV) = screen positive and true cases ÷ all positive screens, a value of 75% or greater would indicate success of the screening method used.

2. Aberrant Behavior Checklist Irritability Subscale Score at Baseline and 9 Weeks Post-intervention [Baseline, Week 9]

   The Aberrant Behavior Checklist (ABC) is a commonly used 58-item parent-rated measure of overall behavioral problems. The Irritability subscale is comprised of 15 items reflecting tantrums, aggression and self injury. Range is 0 to 45, higher scores indicate higher severity. As a preliminary efficacy outcome, it was calculated the average score at baseline and Week 9 post-intervention.

3. Number of Self-Injurious Behavior Events [Baseline, Week 9]

   Direct observation of the frequency of SIB was collected at baseline in a separate observational session after completing the functional analysis and again at Week 9. Investigators set a benchmark of an average decline in the frequency of SIB of 50% within the NAC group.

4. Change in Clinical Global Impression (CGI-I) Scale at 9 Weeks Post-intervention [Week 9]

   The Clinical Global Impression (CGI-I) scale is a 7-item scale from 1 (Very Much Improved) through 4 (No Change) to 7 (Very Much Worse). By convention, scores of 2 (Much Improved) or 1 (Very Much Improved) are used to define positive response.

5. Change in Biomarkers and Possible Mechanisms of Action of NAC in Children With ASD. [Baseline, Week 9]

   Changes amino acid levels before and after NAC treatment: cysteine/cystine and glutathione/glutathione disulfide (GSH/GSSG) ratios (antioxidant effects), glutamate and glutamate/glutamine ratio (glutamate signaling) and GABA levels.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Confirmed diagnosis of Autism Spectrum Disorder (ASD)

• Confirmed presence of moderate Self Injurious Behavior (SIB)

• Score > 16 on the parent-rated Aberrant Behavior Checklist Irritability subscale (moderate level of disruptive behavior)

• Classified as having automatically maintained SIB (determined during screening by a detailed functional analysis)

Exclusion Criteria:

• On a stable medication dose for less than 4 weeks

• Planned change in medication during the 9-week trial

• Had one or more seizures in the last 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Marcus Autism Center	Atlanta	Georgia	United States	30329

Sponsors and Collaborators

• Emory University

Investigators

• Principal Investigator: Lawrence Scahill, MSN, PhD, Emory University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 18, 2019

More Information

Publications

None provided.

• Responsible Party: Lawrence Scahill, MSN, PhD, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT03008889
• Other Study ID Numbers: IRB00088115
• First Posted: Jan 4, 2017
• Last Update Posted: Jan 26, 2021
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Lawrence Scahill, MSN, PhD, Professor, Emory University: Repetitive Self-Injurious Behavior; N-acetylcysteine (NAC)
• Additional relevant MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Self-Injurious Behavior; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Pre-assignment Detail	There were eight consented (or enrolled) participants. Out of the eight participants, one screened failed early, and seven subjects were eligible for the Screening method for classifying self-injurious behavior (SIB) before randomization. Out of those seven, 3 passed screening, and one of the 3 withdrew due to study burden. Two participants were randomized to an intervention (NAC or placebo).

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm will receive gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that will be used a higher than usual doses in this study. N-acetylcysteine: Participants will start with taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28. If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.	Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients. Placebo: Participants will start with taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. The dosing for the placebo will increase in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28. If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo	Total
Arm/Group Description	Participants randomized to the active treatment study arm will receive gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that will be used a higher than usual doses in this study. N-acetylcysteine: Participants will start with taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28. If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.	Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients. Placebo: Participants will start with taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. The dosing for the placebo will increase in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28. If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.	Total of all reporting groups
Overall Participants	1	1	2
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8 (0)	9 (0)	8.5 (0)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	1 100%	2 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 100%	1 100%	2 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Randomized
Description	Goal: randomize 1.75 participants per month
Time Frame	12 months (throughout the duration of the study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study. N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.	Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients. Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.
Measure Participants	1	1
Number [percentage of participants randomized]	100 10000%	100 10000%

2. Primary Outcome

Title	Attrition Rate
Description	Attrition rate is defined as the percent of subjects who did not complete the study. Goal:less than 15% (to indicate that study was acceptable to participants and parents).
Time Frame	12 months (throughout the duration of the study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study. N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.	Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients. Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.
Measure Participants	1	1
Number [percentage of participants]	0 0%	0 0%

3. Primary Outcome

Title	Study Medication Compliance
Description	Goal: at least 70% treatment compliance (tablet counts and drug dairies).
Time Frame	12 months (throughout the duration of the study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study. N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.	Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients. Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.
Measure Participants	1	1
Count of Participants [Participants]	1 100%	1 100%

4. Primary Outcome

Title	Successful Collection of Outcome Measures
Description	Goal: at least 80% collection of essential outcome data to demonstrate the feasibility of data collection procedures.
Time Frame	12 months (throughout the duration of the study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study. N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.	Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients. Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.
Measure Participants	1	1
Count of Participants [Participants]	1 100%	1 100%

5. Primary Outcome

Title	Parent Satisfaction Rating
Description	Goal: at least 80% of parents will agree or strongly agree when asked in an anonymous survey that they would recommend the study and the study treatment to other parents of children with ASD and SIB.
Time Frame	Week 9 (at the end of the study intervention)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study. N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.	Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients. Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.
Measure Participants	1	1
Count of Participants [Participants]	1 100%	1 100%

6. Secondary Outcome

Title	Positive Predictive Value of Screening Method of Classifying Self-injurious Behavior (SIB) by Type.
Description	Goal: at least 75% positive predictive value of our screening method to classify children with automatically maintained self-injurious behavior using a semi-structured interview at screening compared to the findings of five- to six-hour functional analysis at baseline. Only children who appear to have automatically maintained SIB will be referred for the baseline evaluation. Demonstrating a high positive predictive value for the screening method is a necessary prerequisite for launching a larger study. Using the formula: Positive Predictive Value (PPV) = screen positive and true cases ÷ all positive screens, a value of 75% or greater would indicate success of the screening method used.
Time Frame	12 months (duration of the study)

Outcome Measure Data

Analysis Population Description

Screening method for classifying self-injurious behavior (SIB) happened before randomization. Of the 8 participants that consented, one was excluded due to asthma. Results show participants that were classified with repetitive SIB.

Arm/Group Title	Consented Participants Before Randomization
Arm/Group Description	Participants consented in the trial, before randomization.
Measure Participants	7
Count of Participants [Participants]	3 300%

7. Secondary Outcome

Title	Aberrant Behavior Checklist Irritability Subscale Score at Baseline and 9 Weeks Post-intervention
Description	The Aberrant Behavior Checklist (ABC) is a commonly used 58-item parent-rated measure of overall behavioral problems. The Irritability subscale is comprised of 15 items reflecting tantrums, aggression and self injury. Range is 0 to 45, higher scores indicate higher severity. As a preliminary efficacy outcome, it was calculated the average score at baseline and Week 9 post-intervention.
Time Frame	Baseline, Week 9

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study. N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.	Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients. Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.
Measure Participants	1	1
Score at Baseline	31	28
Score at 9-Weeks	23	29

8. Secondary Outcome

Title	Number of Self-Injurious Behavior Events
Description	Direct observation of the frequency of SIB was collected at baseline in a separate observational session after completing the functional analysis and again at Week 9. Investigators set a benchmark of an average decline in the frequency of SIB of 50% within the NAC group.
Time Frame	Baseline, Week 9

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study. N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.	Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients. Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.
Measure Participants	1	1
Baseline	219	93
9-Weeks	59	655

9. Secondary Outcome

Title	Change in Clinical Global Impression (CGI-I) Scale at 9 Weeks Post-intervention
Description	The Clinical Global Impression (CGI-I) scale is a 7-item scale from 1 (Very Much Improved) through 4 (No Change) to 7 (Very Much Worse). By convention, scores of 2 (Much Improved) or 1 (Very Much Improved) are used to define positive response.
Time Frame	Week 9

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study. N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.	Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients. Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.
Measure Participants	1	1
Number [score on a scale]	2	4

10. Secondary Outcome

Title	Change in Biomarkers and Possible Mechanisms of Action of NAC in Children With ASD.
Description	Changes amino acid levels before and after NAC treatment: cysteine/cystine and glutathione/glutathione disulfide (GSH/GSSG) ratios (antioxidant effects), glutamate and glutamate/glutamine ratio (glutamate signaling) and GABA levels.
Time Frame	Baseline, Week 9

Outcome Measure Data

Analysis Population Description

Blood samples were collected and processed in accordance with the protocol. In consultation with our biochemist collaborator, we did not proceed with the multiple laboratory procedures to analyze the sample. Our collaborator indicated that the findings would not be interpretable because we only had two subjects.

Arm/Group Title	Participants Taking NAC	Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm received gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that was used at a higher than usual doses in this study. N-acetylcysteine: Participants started taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.	Participants randomized to placebo received dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contained inactive ingredients. Placebo: Participants started taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects returned to the study site to review adverse events. The dosing for the placebo was increased in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose was gradually increased to 900 mg twice per day for study days 8-28. If this dose was well-tolerated, the dose was increased to 900 three times per day for study days 29-63.
Measure Participants	0	0

Adverse Events

Time Frame	9 weeks
Adverse Event Reporting Description	Each subject was followed by two blinded clinicians. A treating clinician who monitored adverse events and managed the dose of the study medication. An independent evaluator assessed therapeutic response and did not discuss adverse events or medication dose with parent and child.
Arm/Group Title	Participants Taking NAC		Participants Taking Placebo
Arm/Group Description	Participants randomized to the active treatment study arm will receive gradually increasing doses of N-acetylcysteine (NAC) given as a dissolving tablet in juice or water. NAC is an over-the-counter oral dietary supplement that will be used a higher than usual doses in this study. N-acetylcysteine: Participants will start with taking 900mg of NAC once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28. If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.		Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients. Placebo: Participants will start with taking 900mg of the placebo once per day for one week (study days 1-7). At Day 7, parents (or primary caregiver) and subjects will return to the study site to review adverse events. The dosing for the placebo will increase in the same fashion as the active treatment. In the absence of dose limiting adverse events attributable to the study drug, the dose will be gradually increased to 900 mg twice per day for study days 8-28. If this dose is well-tolerated, the dose will be increased to 900 three times per day for study days 29-63.
All Cause Mortality
	Participants Taking NAC		Participants Taking Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Serious Adverse Events
	Participants Taking NAC		Participants Taking Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Participants Taking NAC		Participants Taking Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)
Gastrointestinal disorders
Vomiting	0/1 (0%)	0	1/1 (100%)	1
Constipation	1/1 (100%)	1	0/1 (0%)	0
Diarrhea	0/1 (0%)	0	1/1 (100%)	1
Flatulence	1/1 (100%)	1	0/1 (0%)	0
Increased Appetite	0/1 (0%)	0	1/1 (100%)	1
General disorders
Early morning awakening	1/1 (100%)	1	0/1 (0%)	0
Drowsiness	1/1 (100%)	1	0/1 (0%)	0
Fever	1/1 (100%)	1	0/1 (0%)	0
Weight gain	0/1 (0%)	0	1/1 (100%)	1
Infections and infestations
Rhinitis	1/1 (100%)	1	0/1 (0%)	0
Psychiatric disorders
Aggression	1/1 (100%)	1	0/1 (0%)	0
Agitation	0/1 (0%)	0	1/1 (100%)	1
Skin and subcutaneous tissue disorders
Eczema	1/1 (100%)	1	1/1 (100%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.