An Open-Label Study of N-Acetyl Cysteine in Children With Autism

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00676195
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arm: 1
• Duration (Months): 24
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of the study is to test the tolerability and efficacy of N-Acetyl Cysteine (NAC) in children with Autism.

Condition or Disease	Intervention/Treatment	Phase
Autistic Disorder	Drug: N-Acetyl Cysteine	Phase 2

Detailed Description

N-Acetyl Cysteine (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 N-Acetyl Cysteine 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study of N-Acetyl Cysteine in Autism
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: N-Acetyl Cysteine Dosage of orally administered N-Acetyl Cysteine is as follows: Days 1-30: 900 mg, once per day Days 31-60: 900 mg, twice per day Days 61-90: 900 mg, three times per day	Drug: N-Acetyl Cysteine; Dosage of orally administered N-Acetyl Cysteine is as follows: Days 1-30: 900 mg, once per day Days 31-60: 900 mg, twice per day Days 61-90: 900 mg, three times per day; Other Names: NAC

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events Reported on the Dosage Record and Treatment Emergent Symptom Scale (DOTES) [4, 8, and 12 weeks]

   Number of Participants with adverse events reported on the Dosage Record and Treatment Emergent Symptom Scale (DOTES) during the course of the study as measured at time points (4, 8, and 12 weeks).

Secondary Outcome Measures

1. Social Responsiveness Scale (SRS) [12 weeks]

2. Sensory Profile Questionnaire (SPQ) [12 weeks]

3. Irritability Subscale of the Aberrant Behavior Checklist (ABC) [4, 8, and 12 weeks]

4. Glutathione Metabolism Intermediates in Peripheral Blood Measured by High-performance Liquid Chromatography [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects will be eligible for this study if they participated in the Double-blind, randomized, placebo controlled study of N-Acetyl Cysteine in Autism study at Stanford

University and meet all of the following criteria:

1. Outpatients between 3.0 and 12.11 years of age inclusive

2. Males and females who are physically healthy

3. diagnosis of autism based on Diagnostic and Statistical Manual (DSM-IV-TR) criteria, the Autism Diagnostic Interview-Revised, and expert clinical evaluation

4. Clinical Global Impression Severity rating of 4

5. Care provider who can reliably bring subject to clinic visits, can provide trustworthy ratings, and interacts with subject on a regular basis

6. Ability of subject to swallow the compound

7. Stable concomitant medications for at least 2 weeks

8. No planned changes in psychosocial interventions during the open-label N-Acetyl Cysteine trial

Exclusion Criteria:

1. Diagnostic and Statistical Manual (DSM-IV-TR) diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder, not otherwise specified

2. Active medical problems: unstable seizures, significant physical illness (e.g., serious liver or renal pathology)

3. Pregnancy or sexually active females

4. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Antonio Hardan, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Antonio Hardan, Associate Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT00676195
• Other Study ID Numbers: SU-05062008-1139
• First Posted: May 12, 2008
• Last Update Posted: Mar 29, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Antonio Hardan, Associate Professor, Stanford University: N-Acetyl Cysteine
• Additional relevant MeSH terms: Autistic Disorder; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Arm/Group Title	N-Acetyl Cysteine
Arm/Group Description	N-Acetyl Cysteine: Dosage of orally administered N-Acetyl Cysteine is as follows: Days 1-30: 900 mg, once per day Days 31-60: 900 mg, twice per day Days 61-90: 900 mg, three times per day
Period Title: Overall Study
STARTED	24
COMPLETED	21
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	N-Acetyl Cysteine
Arm/Group Description	N-Acetyl Cysteine: Dosage of orally administered N-Acetyl Cysteine is as follows: Days 1-30: 900 mg, once per day Days 31-60: 900 mg, twice per day Days 61-90: 900 mg, three times per day
Overall Participants	24
Age (Count of Participants)
<=18 years	24 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 8.3%
Male	22 91.7%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events Reported on the Dosage Record and Treatment Emergent Symptom Scale (DOTES)
Description	Number of Participants with adverse events reported on the Dosage Record and Treatment Emergent Symptom Scale (DOTES) during the course of the study as measured at time points (4, 8, and 12 weeks).
Time Frame	4, 8, and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Acetyl Cysteine
Arm/Group Description	N-Acetyl Cysteine: Dosage of orally administered N-Acetyl Cysteine is as follows: Days 1-30: 900 mg, once per day Days 31-60: 900 mg, twice per day Days 61-90: 900 mg, three times per day
Measure Participants	24
Number [number of participants]	17 70.8%

2. Secondary Outcome

Title	Social Responsiveness Scale (SRS)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

No analyses were conducted since it is an open-label trial and data was analyzed in the double-blind phase. Additionally, the main reason for the this phase is to allow participants who were on the placebo during the double-blind phase of NCT00627705 to receive the compound.

Arm/Group Title	Open-Label
Arm/Group Description
Measure Participants	0

3. Secondary Outcome

Title	Sensory Profile Questionnaire (SPQ)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

No analyses were conducted since it is an open-label trial and data was analyzed in the double-blind phase. Additionally, the main reason for the this phase is to allow participants who were on the placebo during the double-blind phase of NCT00627705 to receive the compound.

Arm/Group Title	Open-Label
Arm/Group Description
Measure Participants	0

4. Secondary Outcome

Title	Irritability Subscale of the Aberrant Behavior Checklist (ABC)
Time Frame	4, 8, and 12 weeks

Outcome Measure Data

Analysis Population Description

No analyses were conducted since it is an open-label trial and data was analyzed in the double-blind phase. Additionally, the main reason for the this phase is to allow participants who were on the placebo during the double-blind phase of NCT00627705 to receive the compound.

Arm/Group Title	Open-Label
Arm/Group Description
Measure Participants	0

5. Secondary Outcome

Title	Glutathione Metabolism Intermediates in Peripheral Blood Measured by High-performance Liquid Chromatography
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

No analyses were conducted since it is an open-label trial and data was analyzed in the double-blind phase. Additionally, the main reason for the this phase is to allow participants who were on the placebo during the double-blind phase of NCT00627705 to receive the compound.

Arm/Group Title	Open-Label
Arm/Group Description
Measure Participants	0

Adverse Events

Time Frame	Baseline and 4, 8 and 12 Weeks.
Arm/Group Title	N-Acetyl Cysteine
Arm/Group Description	N-Acetyl Cysteine: Dosage of orally administered N-Acetyl Cysteine is as follows: Days 1-30: 900 mg, once per day Days 31-60: 900 mg, twice per day Days 61-90: 900 mg, three times per day
All Cause Mortality
	N-Acetyl Cysteine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	N-Acetyl Cysteine
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Other (Not Including Serious) Adverse Events
	N-Acetyl Cysteine
	Affected / at Risk (%)	# Events
Total	19/24 (79.2%)
Gastrointestinal disorders
Nausea/Vomiting	2/24 (8.3%)	3
Diarrhea	3/24 (12.5%)	3
Decreased Appetite	5/24 (20.8%)	6
General disorders
Nasal Congestion	6/24 (25%)	6
Insomnia	4/24 (16.7%)	4
Decreased Motor Activity	2/24 (8.3%)	2
Grinding Teeth	2/24 (8.3%)	2
Psychiatric disorders
Depressive Affect	3/24 (12.5%)	3

Limitations/Caveats

This is an open-label trial with a small sample size.

More Information

Certain Agreements

Principal Investigators are NOT 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.