ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03008889
Recruitment Status : Recruiting
First Posted : January 4, 2017
Last Update Posted : July 9, 2018
Sponsor:
Information provided by (Responsible Party):
Lawrence Scahill, MSN, PhD, Emory University

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 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 : July 5, 2018
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


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 Name: 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.





Primary Outcome Measures :
  1. Randomization rate [ Time Frame: 12 months (throughout the duration of the study) ]
    Goal: randomize 1.75 participants per month

  2. Attrition rate [ Time Frame: 12 months (throughout the duration of the study) ]
    Goal:less than 15% (to indicate that study was acceptable to participants and parents).

  3. Study medication compliance [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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. Change in Aberrant Behavior Checklist Irritability Subscale score [ Time Frame: 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. As a preliminary efficacy outcome, we will calculate the average percent change from baseline to Week 9 in the NAC group. We set a benchmark of 25% decline on average. We will also examine the within group improvement on the ABC-Irritability subscale from baseline to Week 9 within the NAC group (paired t-test) and across the groups (ANCOVA).

  3. Number of Self-Injurious Behavior Events [ Time Frame: Baseline, Week 9 ]
    Direct observation of the frequency and severity of SIB will be collected at baseline in a separate observational session after completing the functional analysis and again at Week 9. We set a benchmark of an average decline in the frequency of SIB of 50% within the NAC group. Change in counts and the average severity score within the NAC group will be examined by paired t test and across treatment groups with ANCOVA.

  4. Change in the Improvement item of the Clinical Global Impression (CGI-I) scale [ Time Frame: Week 9 ]
    The Improvement item of 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. We set a benchmark for a CGI-I of 2 or 1 of 50% or more in the NAC group.

  5. To evaluate biomarkers and possible mechanisms of action of NAC in children with ASD. [ Time Frame: Baseline, Week 9 ]
    We will investigate the antioxidant effects and changes amino acid levels before and after NAC treatment. Given the sample size, we do not expect differences between groups. Within the NAC group, we expect increased cysteine/cystine and glutathione/glutathione disulfide (GSH/GSSG) ratios (antioxidant effects), and decreased glutamate and glutamate/glutamine ratio (reduction in glutamate signaling) and increased GABA levels.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   5 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03008889


Contacts
Contact: Lawrence Scahill, MSN, PhD 404-785-9494 lawrence.scahill@emory.edu

Locations
United States, Georgia
Marcus Autism Center Recruiting
Atlanta, Georgia, United States, 30329
Contact: Lawrence Scahill, MSN, PhD    404-785-9467    lawrence.scahill@emory.edu   
Principal Investigator: Lawrence Scahill, MSN, PhD         
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Lawrence Scahill, MSN, PhD Emory University

Responsible Party: Lawrence Scahill, MSN, PhD, Professor, Emory University
ClinicalTrials.gov Identifier: NCT03008889     History of Changes
Other Study ID Numbers: IRB00088115
First Posted: January 4, 2017    Key Record Dates
Last Update Posted: July 9, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
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, Emory University:
Repetitive Self-Injurious Behavior
N-acetylcysteine (NAC)

Additional relevant MeSH terms:
Self-Injurious Behavior
Disease
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Pathologic Processes
Neurodevelopmental Disorders
Mental Disorders
Behavioral Symptoms
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