Autistic DisorderPhase 2NCT00453180
A Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders
A Phase 2 study testing N-acetylcysteine in people with Autistic Disorder and Asperger Syndrome, run by Indiana University at 1 site in United States.
Trial summary
The purpose of this study is to determine whether treatment with oral N-acetylcysteine (NAC) will improve behavior problems often associated with autism spectrum disorders. Read more about this study
- Who is it for?
- Ages 4 to 12 years
- Conditions the study is for
- Autistic Disorder, Asperger Syndrome, Child Development Disorders, Pervasive
- 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
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Nov 2009
- 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 4 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 4 to 12 years.
- Diagnosis of autistic disorder, Asperger's disorder, or PDD NOS.
- If taking concomitant psychotropic medications, the medication must be at a constant dose for 60 days with no dose changes planned for the duration of the trial.
- Able to swallow capsules.
Who cannot join
- Presence of any medical condition that significantly increases risk or hampers assessment (e.g., unstable hypertension or cardiac disease, unstable asthma, kidney disease, unstable seizure disorder, pregnancy or any other medical condition as determined by the investigator).
- Weight < 15 kg.
- Subjects taking concomitant medications or supplements known for their glutamatergic effects (e.g., dextromethorphan, D-cycloserine, amantadine, memantine, lamotrigine, riluzole) or antioxidant properties (high dose vitamin supplements, DMG, TMG, many alternative treatments) within 30 days of the baseline visit with the exception of short term use of dextromethorphan as needed as a cough suppressant. The use of this medicine must be stopped at least 7 days prior to the baseline visit. Regular multivitamins will be allowed.
- Subjects taking daily acetaminophen or nonsteroidal anti-inflammatory drugs within 30 days of the baseline visit.
- Profound mental retardation as evidenced by a mental age below 18 months.
- Subjects taking concomitant medications with the potential for pharmacokinetic or pharmacodynamic drug-drug interactions (e.g., carbamazepine) within 30 days of the baseline visit.
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- Subjects who are likely to experience significant changes in their ongoing psychosocial or medical treatments for autism over the course of the trial (e.g., initiation of new behavioral therapy, initiation of new medication or alternative treatment [e.g., chelation]). Minor changes in ongoing treatment (e.g., missed therapy sessions due to holiday/vacation; planned break in therapy due to school holidays) will not be considered significant.
- History of prior treatment with NAC.
- Evidence of hypersensitivity/allergy to NAC.
- Presence of certain neurodevelopmental disorders such as Fragile X Syndrome, Tuberous Sclerosis, or other neurological disorders known to be associated with autism or autistic features.
- Diagnosis of Rett's disorder, childhood disintegrative disorder, schizophrenia, bipolar disorder, another psychotic disorder, or substance abuse disorder.
Trial locations and contacts
1 site in 1 country.
United States1 site
Riley Hospital, Riley Child and Adolescent Psychiatry Clinic
Indianapolis, Indiana, 46020
About this study
Official title: A Pilot Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders
The purpose of this study is to determine whether treatment with oral N-acetylcysteine (NAC) will improve behavior problems often associated with autism spectrum disorders.
Read the detailed description
Autism is increasingly being recognized as a common disorder with enormous public health significance. The core symptoms of autism include severe deficits in social relatedness and communication, and interfering repetitive behavior. No medications have been shown to consistently improve any of these symptoms.
The central hypothesis of this study is that NAC will improve behavioral manifestations of autism which may include core or associated symptoms. We plan to test our hypothesis and complete the objectives of this project by pursuing the following specific aims:
- Evaluate the efficacy of oral NAC in a 12-week, double-blind, placebo-controlled study involving 32 children and adolescents with autism spectrum disorders.
- Evaluate the safety and tolerability of oral NAC in 32 children and adolescents with autism spectrum disorders.
- Being tested
- N-acetylcysteine, Placebo
- Keywords
- Autistic Disorder, Asperger's, PDD NOS, Pervasive Developmental Disorder, Autism, N-acetylcysteine, acetylcysteine, NAC, antioxidant, treatment, core symptoms, Autism Spectrum Disorders, Asperger's Disorder, Pervasive Developmental Disorder Not Otherwise Specified, Pervasive Developmental Disorders
- Medical subject headings
- Autistic Disorder, Asperger Syndrome, Child Development Disorders, Pervasive, Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Capsules available in 300 mg or 600mg strength. Target dose of n-acetylcysteine will be 60mg/kg/day TID. Dosage will be increased to this target dose from week 1 to week 3 barring side effects. Dose reduction will be allowed at any time for adverse side effects. Maximum dose of n-acetylcysteine will be 4200mg/day.
PlaceboDrug
Subjects randomized to placebo arm will receive placebo pill for duration of study.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Target dose for n-acetylcysteine is 60 mg/kg/day. Capsules available in 300 mg and 600 mg strengths. Receives: Drug: N-acetylcysteine |
| 2 | Placebo comparator | Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. 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.
Clinical Global Impression - Severity
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Measured: Week 12
Clinical Global Impression - Improvement
Clinical Global Impression - Improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment.
The CGI-I scale ranges from 1 to 7 (1=very much improved; 2=much improved, 3=minimally Improved, 4=no change, 5=minimally worse, 6= much worse and 7=very much worse). Participants with a CGI-I score of 1 or 2 were classified as improved. Participants with a CGI score of 3, 4 or 5 were classified as no response. No participants scored 6 or 7.
Measured: Week 12
Secondary outcomes (4)
Aberrant Behavior Checklist
The Aberrant Behavior Checklist (ABC) is a 58-item measure of maladaptive behaviors and is used as a measure of drug effects. Each of the 58 items are rated from 0 (not at all) to 3 (severe).The ABC has 5 subscales: Irritability (15 items) ranging from 0 (not at all) to 45 (severe), Lethargy (16 items) ranging from 0 (not at all) to 48 (severe), Stereotypy (7 items) ranging from 0 (not at all) to 21 (severe), Hyperactivity (16 items) ranging from 0 (not at all) to 48 (severe), and Inappropriate Speech (4 items) ranging from 0 (not at all) to 12 (severe). Higher scores indicate a higher level of maladaptive behavior.
Measured: Week 12
Social Responsiveness Scale
The Social Responsiveness Scale (SRS) is a 65-item scale that assesses social impairment in the aspects of social awareness, social cognition, social communication, social motivation and autistic mannerisms. Each item is scored from 0 (not true) to 3 (almost always true). The total SRS raw score may range from 0-195, where higher scores indicate greater severity.
Measured: Week 12
Pervasive Developmental Disorder Behavior Index
The PDD Behavior Inventory (PDDBI) is a rating scale filled out by caregivers or teachers that was designed to assess children having a Pervasive Developmental Disorder (PDD; autism, Asperger disorder, PDD-NOS, or childhood disintegrative disorder). Both adaptive and maladaptive behaviors are assessed in the scale, making it useful for treatment studies in which decreases in maladaptive behaviors and improvements in adaptive social and language skills relevant to PDD are expected.
Measured: Week 12
Vineland Adaptive Behavior Scales-II (VABS-II)
The VABS-II is a semi-structured interview designed to assess adaptive functioning in the domains of communication, daily living skills and socialization. Items in each domain are rated as either 0 (does not), 1(sometimes) or 2(independently) performs a given behavior or skill. The communication domain has 99 items with scores ranging from 0-198. The daily living skills domain has 109 items with scores ranging from 0-218. The socialization domain has 99 items with scores ranging from 0-198. The domains scores are combined to form the adaptive composite score (ranging from 20-160). The raw scores from the communication, daily living skills and socialization domains along with the composite score were selected for use in this study. Higher scores indicate a higher level of adaptive functioning.
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2007 (estimated)
- Study startMar 2007
- Primary completionAug 2009
- Study completionNov 2009
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Autistic DisorderStudies of the same condition, open and under way.
- More trials run by Indiana 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Autism Research
- Responsible party
- Sponsor
- Investigators
- Martin H. Plawecki, M.D., Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00453180
- Sponsor's protocol ID
- 0611-10
- Status last verified
- May 2017
- First submitted
- 27 Mar 2007
- Last updated
- 14 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Wink LK, Adams R, Wang Z, Klaunig JE, Plawecki MH, Posey DJ, McDougle CJ, Erickson CA. A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. Mol Autism. 2016 Apr 21;7:26. doi: 10.1186/s13229-016-0088-6. eCollection 2016.
PubMed 27103982Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
PubMed 37811711
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders
- ClinicalTrials.gov ID
- NCT00453180
- Acronym / sponsor ID
- 0611-10
- Keywords
- Autistic Disorder, Asperger's, PDD NOS, Pervasive Developmental Disorder, Autism, N-acetylcysteine, acetylcysteine, NAC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Alliance for Autism Research
- Study start
- Mar 2007
- Primary completion
- Aug 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 28 Mar 2007 (estimated)
- Results
- Posted 14 Jun 2017
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 determine whether treatment with oral N-acetylcysteine (NAC) will improve behavior problems often associated with autism spectrum disorders.
Detailed description
Autism is increasingly being recognized as a common disorder with enormous public health significance. The core symptoms of autism include severe deficits in social relatedness and communication, and interfering repetitive behavior. No medications have been shown to consistently improve any of these symptoms.
The central hypothesis of this study is that NAC will improve behavioral manifestations of autism which may include core or associated symptoms. We plan to test our hypothesis and complete the objectives of this project by pursuing the following specific aims:
- Evaluate the efficacy of oral NAC in a 12-week, double-blind, placebo-controlled study involving 32 children and adolescents with autism spectrum disorders.
- Evaluate the safety and tolerability of oral NAC in 32 children and adolescents with autism spectrum disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: N-acetylcysteineTarget dose for n-acetylcysteine is 60 mg/kg/day. Capsules available in 300 mg and 600 mg strengths. |
| 2 | Placebo comparator | Drug: PlaceboSubjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients. |
Who may qualify
- Ages
- 4 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Age 4 to 12 years.
- Diagnosis of autistic disorder, Asperger's disorder, or PDD NOS.
- If taking concomitant psychotropic medications, the medication must be at a constant dose for 60 days with no dose changes planned for the duration of the trial.
- Able to swallow capsules.
Key exclusion criteria (11 listed)
- Presence of any medical condition that significantly increases risk or hampers assessment (e.g., unstable hypertension or cardiac disease, unstable asthma, kidney disease, unstable seizure disorder, pregnancy or any other medical condition as determined by the investigator).
- Weight < 15 kg.
- Subjects taking concomitant medications or supplements known for their glutamatergic effects (e.g., dextromethorphan, D-cycloserine, amantadine, memantine, lamotrigine, riluzole) or antioxidant properties (high dose vitamin supplements, DMG, TMG, many alternative treatments) within 30 days of the baseline visit with the exception of short term use of dextromethorphan as needed as a cough suppressant. The use of this medicine must be stopped at least 7 days prior to the baseline visit. Regular multivitamins will be allowed.
- Subjects taking daily acetaminophen or nonsteroidal anti-inflammatory drugs within 30 days of the baseline visit.
- Profound mental retardation as evidenced by a mental age below 18 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-acetylcysteineCapsules available in 300 mg or 600mg strength. Target dose of n-acetylcysteine will be 60mg/kg/day TID. Dosage will be increased to this target dose from week 1 to week 3 barring side effects. Dose reduction will be allowed at any time for adverse side effects. Maximum dose of n-acetylcysteine will be 4200mg/day. | Drug | 1 |
| PlaceboSubjects randomized to placebo arm will receive placebo pill for duration of study. | Drug | 2 |
Primary outcome
Clinical Global Impression - Severity
Time frame: Week 12
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Clinical Global Impression - Improvement
Time frame: Week 12
Clinical Global Impression - Improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7 (1=very much improved; 2=much improved, 3=minimally Improved, 4=no change, 5=minimally worse, 6= much worse and 7=very much worse). Participants with a CGI-I score of 1 or 2 were classified as improved. Participants with a CGI score of 3, 4 or 5 were classified as no response. No participants scored 6 or 7.
4 secondary outcomes
Aberrant Behavior Checklist
Time frame: Week 12
Social Responsiveness Scale
Time frame: Week 12
Pervasive Developmental Disorder Behavior Index
Time frame: Week 12
Vineland Adaptive Behavior Scales-II (VABS-II)
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27103982Wink LK, Adams R, Wang Z, Klaunig JE, Plawecki MH, Posey DJ, McDougle CJ, Erickson CA. A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. Mol Autism. 2016 Apr 21;7:26. doi: 10.1186/s13229-016-0088-6. eCollection 2016.
- Derived from this study: PubMed 37811711Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
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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.
Martin H. Plawecki, M.D. principal investigator
Indiana 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 Autistic Disorder and Asperger Syndrome, run by Indiana 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 11 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 14 Jun 2017. 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 14 Jun 2017). 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?
Clinical Global Impression - Severity (time frame: Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00453180, which also lists 2 linked publications.
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 14 Jun 2017.