Autistic DisorderPhase 2NCT00627705

A Study of N-Acetyl Cysteine in Children With Autism

A Phase 2 study testing N-Acetyl Cysteine in people with Autistic Disorder, run by Stanford University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 3 to 12 years
Conditions the study is for: Autistic Disorder
What is being tested?: N-Acetyl Cysteine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 43 participants
Where: 1 siteUnited States
Study dates: Feb 2008to Sep 2010
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 3 to 12 years
All sexes
No healthy volunteers
Child

Who may be able to join

Outpatients between 3.0 and 12.11 years of age inclusive
Males and females who are physically healthy
diagnosis of autism based Diagnostic and Statistical Manual (DSM-IV-TR) criteria, the Autism Diagnostic Interview-Revised, and expert clinical evaluation
Clinical Global Impression Severity rating of 4
Care provider who can reliably bring subject to clinic visits, can provide trustworthy ratings, and interacts with subject on a regular basis
Ability of subject to swallow the compound
Stable concomitant medications for at least 2 weeks
No planned changes in psychosocial interventions during the open-label N-Acetyl Cysteine trial

Who cannot join

DSM-IV-TR diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified
Prior adequate trial of N-Acetyl Cysteine
Active medical problems: unstable seizures, significant physical illness (e.g., serious liver or renal pathology)
Pregnancy or sexually active females
Subjects taking antioxidant agents and glutathione prodrugs will be excluded from the study except if they have been off these compounds for at least 4 weeks

Trial locations and contacts

1 site in 1 country.

United States1 site

Stanford University School of Medicine
Stanford, California, 94305

Other trials in United States

About this study

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

The purpose of the study is to test the tolerability and efficacy of N-Acetyl Cysteine (NAC) in children with Autism. NAC is a compound that increases the levels of Glutathione, the body's main antioxidant. Glutathione is a compound in the blood that is part of a natural defense system (the antioxidant system). Anti-oxidants protect the body from damage caused by internal toxins called "free radicals." It is possible that children with Autism tend to have lower levels of glutathione, an important compound in our bodies that helps combat the effects of toxic free radicals.

We hope that by studying the antioxidant system in more detail, we will increase our understanding of the reasons why people develop Autism so that we can design better ways to treat individuals with this condition. This study is meant to test the safety tolerability of NAC and its effectiveness in the treatment of behavioral difficulties in children with autism. It will also examine the possible benefit of this agent in improving the core deficits in autism such as social deficits.

Conditions: Autistic Disorder
Being tested: N-Acetyl Cysteine, Placebo - sugar pill
Medical subject headings: Autistic Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

N-Acetyl CysteineDrug
Also called NAC
Phase 1: Oral, 900 mg daily for 4 weeks Phase 2: Oral, 900 mg twice daily 4 weeks Phase 3: Oral, 900 mg three times daily for 4 weeks
Entire intervention lasts for 12 weeks (drug administration is continuous).
Placebo - sugar pillOther
Also called Placebo
Phase 1: Oral, 900 mg daily for 4 weeks Phase 2: Oral, 900 mg twice daily 4 weeks Phase 3: Oral, 900 mg three times daily for 4 weeks
Entire intervention lasts for 12 weeks (drug administration is continuous).

Study groups in NCT00627705
Study group	Role	What they receive
N-Acetyl Cysteine	Active comparator	active compound N-Acetyl Cysteine Receives: Drug: N-Acetyl Cysteine
Sugar pill	Placebo comparator	Placebo or sugar pill Receives: Other: Placebo - sugar pill

What is being measured

The primary outcome is the main question the study is designed to answer.

Total Number of Subjects With Reported Side Effects as Assessed by Dosage Record and Treatment Emergent Symptom Scale (DOTES)
The Dosage Record and Treatment Emergent Symptom Scale (DOTES) provides information on the presence, frequency, and severity of side effects reported during the course of the trial.
Measured: 4, 8, and 12 weeks
The Clinical Global Rating Scale (CGRS) Improvement Subscale Score
Score range 1-7 (lower score mean more improvement compared to baseline)
Measured: 12 weeks
Glutathione (GSH) Levels in Peripheral Blood, Measured by State-of-the-art High-performance Liquid Chromatography (HPLC)
Data not collected. The laboratory was not able to measure Glutathione levels.
Measured: 12 weeks
Irritability Subscale of the Aberrant Behavior Checklist (ABC)
Aberrant Behavior Checklist (ABC) Irritability Subscale Score (range 0-45); higher scores mean higher irritability
Measured: baseline and 12 weeks

Secondary outcomes (4)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2008Sep 2010

First posted3 Mar 2008 (estimated)
Study startFeb 2008
Primary completionSep 2010
Study completionSep 2010

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 (1)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 Stanford 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: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00627705
Sponsor's protocol ID: SU-02012008-995
Other IDs: 10142
Status last verified: Apr 2017
First submitted: 22 Feb 2008
Last updated: 18 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes

Publications

Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, Frazier TW, Tirouvanziam R. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012 Jun 1;71(11):956-61. doi: 10.1016/j.biopsych.2012.01.014. Epub 2012 Feb 18.
PubMed 22342106

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Autistic Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 18 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Double-blind , Randomized, Placebo Controlled Study of N-Acetyl Cysteine in Autism.
ClinicalTrials.gov ID: NCT00627705
Acronym / sponsor ID: SU-02012008-995
Conditions: Autistic Disorder
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 43 participants (actual)
Lead sponsor: Stanford UniversityUniversity, hospital or other
Study start: Feb 2008
Primary completion: Sep 2010 (actual)
Study completion: Sep 2010 (actual)
First posted: 3 Mar 2008 (estimated)
Results: Posted 18 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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
N-Acetyl Cysteine	Active comparator	Drug: N-Acetyl Cysteineactive compound N-Acetyl Cysteine
Sugar pill	Placebo comparator	Other: Placebo - sugar pillPlacebo or sugar pill

Who may qualify

Ages: 3 to 12 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (8 listed)

Outpatients between 3.0 and 12.11 years of age inclusive
Males and females who are physically healthy
diagnosis of autism based Diagnostic and Statistical Manual (DSM-IV-TR) criteria, the Autism Diagnostic Interview-Revised, and expert clinical evaluation
Clinical Global Impression Severity rating of 4
Care provider who can reliably bring subject to clinic visits, can provide trustworthy ratings, and interacts with subject on a regular basis

Key exclusion criteria (5 listed)

DSM-IV-TR diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified
Prior adequate trial of N-Acetyl Cysteine
Active medical problems: unstable seizures, significant physical illness (e.g., serious liver or renal pathology)
Pregnancy or sexually active females
Subjects taking antioxidant agents and glutathione prodrugs will be excluded from the study except if they have been off these compounds for at least 4 weeks

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-Acetyl CysteineAlso: NACPhase 1: Oral, 900 mg daily for 4 weeks Phase 2: Oral, 900 mg twice daily 4 weeks Phase 3: Oral, 900 mg three times daily for 4 weeks Entire intervention lasts for 12 weeks (drug administration is continuous).	Drug	N-Acetyl Cysteine
Placebo - sugar pillAlso: PlaceboPhase 1: Oral, 900 mg daily for 4 weeks Phase 2: Oral, 900 mg twice daily 4 weeks Phase 3: Oral, 900 mg three times daily for 4 weeks Entire intervention lasts for 12 weeks (drug administration is continuous).	Other	Sugar pill

Primary outcome

Total Number of Subjects With Reported Side Effects as Assessed by Dosage Record and Treatment Emergent Symptom Scale (DOTES)
Time frame: 4, 8, and 12 weeks
The Dosage Record and Treatment Emergent Symptom Scale (DOTES) provides information on the presence, frequency, and severity of side effects reported during the course of the trial.
The Clinical Global Rating Scale (CGRS) Improvement Subscale Score
Time frame: 12 weeks
Score range 1-7 (lower score mean more improvement compared to baseline)
Glutathione (GSH) Levels in Peripheral Blood, Measured by State-of-the-art High-performance Liquid Chromatography (HPLC)
Time frame: 12 weeks
Data not collected. The laboratory was not able to measure Glutathione levels.
Irritability Subscale of the Aberrant Behavior Checklist (ABC)
Time frame: baseline and 12 weeks
Aberrant Behavior Checklist (ABC) Irritability Subscale Score (range 0-45); higher scores mean higher irritability

4 secondary outcomes

The Aberrant Behavior Checklist Total Score (ABC)
Time frame: 4, 8, and 12 weeks
Social Responsiveness Scale (SRS)
Time frame: 12 weeks
Sensory Profile Questionnaire (SPQ)
Time frame: 12 weeks
Glutathione (GSH) Metabolism Intermediates in Peripheral Blood
Time frame: 12 weeks

Results and safety

Results posted to the registry on 18 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
N-Acetyl Cysteine	15	13
Sugar Pill	18	12

Primary outcome: Total Number of Subjects With Reported Side Effects as Assessed by Dosage Record and Treatment Emergent Symptom Scale (DOTES)

Time frame: 4, 8, and 12 weeks. Number. Unit: participants

Measure	N-Acetyl Cysteine n = 14	Sugar Pill n = 15
Total Number of Subjects with GI adverse Events	11	7
Constipation	3	2
Nausea/Vomiting	6	3
Diarrhea	3	1
Increased Appetite	2	0
Decreased Appetite	2	3
Akathisia	1	0
Excitement/Agitation	2	3

Population analysed: We analyzed subjects who had follow-up data available.

Primary outcome: The Clinical Global Rating Scale (CGRS) Improvement Subscale Score

Time frame: 12 weeks. Mean (Standard Deviation). Unit: score (range 1-7)

Measure	N-Acetyl Cysteine n = 14	Sugar Pill n = 15
Value	3.2 (0.9)	2.9 (1.1)

N-Acetyl Cysteine vs Sugar Pill: p = 0.449, mixed effects regression models

Population analysed: We analyzed subjects who had follow-up data available.

Primary outcome: Glutathione (GSH) Levels in Peripheral Blood, Measured by State-of-the-art High-performance Liquid Chromatography (HPLC)

Time frame: 12 weeks

Population analysed: Data not collected.

Primary outcome: Irritability Subscale of the Aberrant Behavior Checklist (ABC)

Time frame: baseline and 12 weeks. Mean (Standard Deviation). Unit: Score (range 0-45)

Measure	N-Acetyl Cysteine n = 14	Sugar Pill n = 15
Baseline ABC-I Score	16.9 (7.9)	14.8 (9.6)
Week 12 ABC-I Score	7.2 (5.7)	13.1 (9.9)

N-Acetyl Cysteine vs Sugar Pill: p <.001, Mixed effects regression models

Population analysed: We analyzed subjects who had follow-up data available.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline and 4, 8 and 12 Weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
N-Acetyl Cysteine	0 of 14 (0%)	13 of 14 (92.9%)	Not reported
Sugar Pill	0 of 15 (0%)	14 of 15 (93.3%)	Not reported

Limitations and caveats (from the sponsor): The sample size was relatively small and the age range was narrow, which limits the generalizability of the findings. Most subjects were taking psychotropic medications and were receiving behavioral interventions.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 22342106Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, Frazier TW, Tirouvanziam R. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012 Jun 1;71(11):956-61. doi: 10.1016/j.biopsych.2012.01.014. Epub 2012 Feb 18.
Individual participant dataSharing planned: Yes

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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.

Antonio Hardan, MD principal investigator

Stanford 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-Acetyl Cysteine in people with Autistic Disorder, run by Stanford 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 8 inclusion and 5 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 18 May 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 18 May 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?

Total Number of Subjects With Reported Side Effects as Assessed by Dosage Record and Treatment Emergent Symptom Scale (DOTES) (time frame: 4, 8, and 12 weeks). The study lists 4 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 NCT00627705, which also lists 1 linked publication.

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 18 May 2017.