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| Name | Class |
|---|---|
| National Alliance for Autism Research | OTHER |
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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Target dose for n-acetylcysteine is 60 mg/kg/day. Capsules available in 300 mg and 600 mg strengths. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N-acetylcysteine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Martin H. Plawecki, M.D. | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Riley Hospital, Riley Child and Adolescent Psychiatry Clinic | Indianapolis | Indiana | 46020 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27103982 | Background | 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. | |
| 37811711 | Derived | Iffland 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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| ID | Title | Description |
|---|---|---|
| FG000 | N-acetylcysteine | Target dose for n-acetylcysteine is 60 mg/kg/day. Capsules available in 300 mg and 600 mg strengths. N-acetylcysteine: 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. |
| FG001 | Placebo | Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients. Placebo: Subjects randomized to placebo arm will receive placebo pill for duration of study. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | N-acetylcysteine | Target dose for n-acetylcysteine is 60 mg/kg/day. Capsules available in 300 mg and 600 mg strengths. N-acetylcysteine: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | No | Week 12 |
|
Twelve Weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | N-acetylcysteine | Target dose for n-acetylcysteine is 60 mg/kg/day. Capsules available in 300 mg and 600 mg strengths. N-acetylcysteine: 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aggression | Psychiatric disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Craig Erickson | Cincinnati Childrens Hospital | 513-636-6258 | craig.erickson@cchmc.org |
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| ID | Term |
|---|---|
| D001321 | Autistic Disorder |
| D020817 | Asperger Syndrome |
| D002659 | Child Development Disorders, Pervasive |
| D000067877 | Autism Spectrum Disorder |
| ID | Term |
|---|---|
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000111 | Acetylcysteine |
| ID | Term |
|---|---|
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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|
| Placebo | Drug | Subjects randomized to placebo arm will receive placebo pill for duration of study. |
|
| 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. | 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. | 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. | Week 12 |
| BG001 | Placebo | Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients. Placebo: Subjects randomized to placebo arm will receive placebo pill for duration of study. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| 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. | Count of Participants | Participants |
|
| OG001 | Placebo | Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients. Placebo: Subjects randomized to placebo arm will receive placebo pill for duration of study. |
|
|
| Primary | 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. | Posted | Count of Participants | Participants | Week 12 |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | Week 12 |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | Week 12 |
|
|
|
| Secondary | 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. | Less than 25% of participants in each group received a score on the PDDBI due to a significant floor effect. As a result, the data for these participants are not considered reliable given the significant floor effect. | Posted | Week 12 |
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | Week 12 |
|
|
|
| 0 |
| 16 |
| 16 |
| 16 |
| EG001 | Placebo | Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain in active ingredients. Placebo: Subjects randomized to placebo arm will receive placebo pill for duration of study. | 0 | 15 | 15 | 15 |
| Accidental arm injury | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Appetite Increase | General disorders | Non-systematic Assessment |
|
| Behavior Worse | Psychiatric disorders | Non-systematic Assessment |
|
| Cold | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Difficulty Falling Asleep | Psychiatric disorders | Non-systematic Assessment |
|
| Ear Infection | Ear and labyrinth disorders | Non-systematic Assessment |
|
| Dry Mouth | General disorders | Non-systematic Assessment |
|
| Elevated liver enzymes | Hepatobiliary disorders | Non-systematic Assessment |
|
| Encopresis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Enuresis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Hand Movements | Nervous system disorders | Non-systematic Assessment |
|
| Fever | General disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Hives | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Hypoglycemia | Endocrine disorders | Non-systematic Assessment |
|
| Increased Swelling of Feet | Vascular disorders | Non-systematic Assessment |
|
| Influenza | Infections and infestations | Non-systematic Assessment |
|
| Intermittent Dyspepsia | Gastrointestinal disorders | Non-systematic Assessment |
|
| Itchy Skin | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Nasal Cauterization | Surgical and medical procedures | Non-systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Poison Ivy | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Localized Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Scabies | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Skin Picking/SIB | Psychiatric disorders | Non-systematic Assessment |
|
| Stuttering | Nervous system disorders | Non-systematic Assessment |
|
| Swollen neck lymph node of unknown origin | Endocrine disorders | Non-systematic Assessment |
|
| Threats to hurt self | Psychiatric disorders | Non-systematic Assessment |
|
| Urinary Tract Infection | Renal and urinary disorders | Non-systematic Assessment |
|
| Weight Gain | General disorders | Non-systematic Assessment |
|
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| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| Stereotypy |
|
| Hyperactivity |
|
| Inappropriate Speech |
|
| Socialization |
|
| Adaptive Behavior Composite |
|