Autism Spectrum DisorderPhase 2NACNCT03008889
A Feasibility Study of N-acetylcysteine for Self-injurious Behavior in Children With Autism Spectrum Disorder
A Phase 2 study testing N-acetylcysteine in people with Autism Spectrum Disorder, run by Emory University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 5 to 12 yearsHealthy volunteers can take part
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jul 2018to 12 Sep 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 12 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Autism Spectrum Disorder
- Being tested
- N-acetylcysteine, Placebo
- Keywords
- Repetitive Self-Injurious Behavior, N-acetylcysteine (NAC)
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called NAC
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Participants taking NAC | Experimental | 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. Receives: Drug: N-acetylcysteine |
| Participants taking Placebo | Placebo comparator | Participants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Randomized
Goal: randomize 1.75 participants per month
Measured: 12 months (throughout the duration of the study)
Attrition Rate
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).
Measured: 12 months (throughout the duration of the study)
Study Medication Compliance
Goal: at least 70% treatment compliance (tablet counts and drug dairies).
Measured: 12 months (throughout the duration of the study)
Successful Collection of Outcome Measures
Goal: at least 80% collection of essential outcome data to demonstrate the feasibility of data collection procedures.
Measured: 12 months (throughout the duration of the study)
Parent Satisfaction Rating
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.
Measured: Week 9 (at the end of the study intervention)
Secondary outcomes (5)
Positive Predictive Value of Screening Method of Classifying Self-injurious Behavior (SIB) by Type.
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.
Measured: 12 months (duration of the study)
Aberrant Behavior Checklist Irritability Subscale Score at Baseline and 9 Weeks Post-intervention
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.
Measured: Baseline, Week 9
Number of Self-Injurious Behavior Events
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.
Measured: Baseline, Week 9
Change in Clinical Global Impression (CGI-I) Scale at 9 Weeks Post-intervention
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.
Measured: Week 9
Change in Biomarkers and Possible Mechanisms of Action of NAC in Children With ASD.
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.
Measured: Baseline, Week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2017 (estimated)
- Study start5 Jul 2018
- Primary completion12 Sep 2019
- Study completion12 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lawrence Scahill, MSN, PhD, Emory University
- Investigators
- Lawrence Scahill, MSN, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03008889
- Sponsor's protocol ID
- IRB00088115
- Acronym
- NAC
- Status last verified
- Nov 2020
- First submitted
- 28 Dec 2016
- Last updated
- 26 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility Study of N-acetylcysteine for Self-injurious Behavior in Children With Autism Spectrum Disorder
- ClinicalTrials.gov ID
- NCT03008889
- Acronym / sponsor ID
- NAC / IRB00088115
- Conditions
- Autism Spectrum Disorder
- Keywords
- Repetitive Self-Injurious Behavior, N-acetylcysteine (NAC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- 5 Jul 2018 (actual)
- Primary completion
- 12 Sep 2019 (actual)
- Study completion
- 12 Sep 2019 (actual)
- First posted
- 4 Jan 2017 (estimated)
- Results
- Posted 16 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants taking NAC | Experimental | Drug: N-acetylcysteineParticipants 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. |
| Participants taking Placebo | Placebo comparator | Drug: PlaceboParticipants randomized to placebo will receive dissolving tablets identical in size and appearance to the active treatment. Placebo capsules contain inactive ingredients. |
Who may qualify
- Ages
- 5 to 12 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: NACParticipants 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. | Drug | Participants taking NAC |
| PlaceboParticipants 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. | Drug | Participants taking Placebo |
Primary outcome
Percentage of Participants Randomized
Time frame: 12 months (throughout the duration of the study)
Goal: randomize 1.75 participants per month
Attrition Rate
Time frame: 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).
Study Medication Compliance
Time frame: 12 months (throughout the duration of the study)
Goal: at least 70% treatment compliance (tablet counts and drug dairies).
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.
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.
5 secondary outcomes
Positive Predictive Value of Screening Method of Classifying Self-injurious Behavior (SIB) by Type.
Time frame: 12 months (duration of the study)
Aberrant Behavior Checklist Irritability Subscale Score at Baseline and 9 Weeks Post-intervention
Time frame: Baseline, Week 9
Number of Self-Injurious Behavior Events
Time frame: Baseline, Week 9
Change in Clinical Global Impression (CGI-I) Scale at 9 Weeks Post-intervention
Time frame: Week 9
Change in Biomarkers and Possible Mechanisms of Action of NAC in Children With ASD.
Time frame: Baseline, Week 9
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence Scahill, MSN, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-acetylcysteine in people with Autism Spectrum Disorder, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Randomized (time frame: 12 months (throughout the duration of the study)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2021.