Trial Outcomes & Findings for A Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders (NCT NCT00453180)
NCT ID: NCT00453180
Last Updated: 2017-06-14
Results Overview
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.
COMPLETED
PHASE2
31 participants
Week 12
2017-06-14
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
15
|
|
Overall Study
COMPLETED
|
13
|
12
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Adverse Event
|
1
|
2
|
Baseline Characteristics
A Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders
Baseline characteristics by cohort
| Measure |
N-acetylcysteine
n=16 Participants
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.
|
Placebo
n=15 Participants
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.
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
7.6 Years
STANDARD_DEVIATION 2.5 • n=5 Participants
|
8.2 Years
STANDARD_DEVIATION 2.9 • n=7 Participants
|
7.8 Years
STANDARD_DEVIATION 2.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
15 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Clinical Global Impression-Severity
1. Normal, not al all ill
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Clinical Global Impression-Severity
2. Borderline ill
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Clinical Global Impression-Severity
3..Mildly ill
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Clinical Global Impression-Severity
4. Moderatly ill
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Clinical Global Impression-Severity
5. Markedly ill
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Clinical Global Impression-Severity
6. Severly ill
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Clinical Global Impression-Severity
7. Extremly ill
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 12The 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.
Outcome measures
| Measure |
N-acetylcysteine
n=13 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Clinical Global Impression - Severity
1.Normal, not at all ill
|
0 Participants
|
0 Participants
|
|
Clinical Global Impression - Severity
2.Borderline ill
|
0 Participants
|
0 Participants
|
|
Clinical Global Impression - Severity
3.Mildly ill
|
3 Participants
|
0 Participants
|
|
Clinical Global Impression - Severity
4.Moderately ill
|
5 Participants
|
12 Participants
|
|
Clinical Global Impression - Severity
5.Markedly ill
|
5 Participants
|
0 Participants
|
|
Clinical Global Impression - Severity
6.Severely ill
|
0 Participants
|
0 Participants
|
|
Clinical Global Impression - Severity
7.Extremely ill
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Week 12Clinical 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.
Outcome measures
| Measure |
N-acetylcysteine
n=13 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Clinical Global Impression - Improvement
Improved
|
6 Participants
|
5 Participants
|
|
Clinical Global Impression - Improvement
No Response
|
7 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Week 12The 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.
Outcome measures
| Measure |
N-acetylcysteine
n=13 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Aberrant Behavior Checklist
Irritablity
|
14.9 units on a scale
Standard Deviation 14.0
|
12.0 units on a scale
Standard Deviation 7.3
|
|
Aberrant Behavior Checklist
Lethargy
|
10.0 units on a scale
Standard Deviation 7.1
|
7.9 units on a scale
Standard Deviation 4.7
|
|
Aberrant Behavior Checklist
Stereotypy
|
3.9 units on a scale
Standard Deviation 5.1
|
5.8 units on a scale
Standard Deviation 4.0
|
|
Aberrant Behavior Checklist
Hyperactivity
|
17.4 units on a scale
Standard Deviation 16.4
|
15.1 units on a scale
Standard Deviation 10.8
|
|
Aberrant Behavior Checklist
Inappropriate Speech
|
4.1 units on a scale
Standard Deviation 3.9
|
5.14 units on a scale
Standard Deviation 3.5
|
SECONDARY outcome
Timeframe: Week 12The 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.
Outcome measures
| Measure |
N-acetylcysteine
n=13 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Social Responsiveness Scale
|
85.8 units on a scale
Standard Deviation 34.9
|
89.1 units on a scale
Standard Deviation 26.3
|
SECONDARY outcome
Timeframe: Week 12Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 12The 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.
Outcome measures
| Measure |
N-acetylcysteine
n=13 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Vineland Adaptive Behavior Scales-II (VABS-II)
Communication
|
88.5 units on a scale
Standard Deviation 32.5
|
95.0 units on a scale
Standard Deviation 30.3
|
|
Vineland Adaptive Behavior Scales-II (VABS-II)
Daily Living Skills
|
99.0 units on a scale
Standard Deviation 37.1
|
98.6 units on a scale
Standard Deviation 33.4
|
|
Vineland Adaptive Behavior Scales-II (VABS-II)
Socialization
|
71.7 units on a scale
Standard Deviation 18.7
|
75.9 units on a scale
Standard Deviation 21.0
|
|
Vineland Adaptive Behavior Scales-II (VABS-II)
Adaptive Behavior Composite
|
62.9 units on a scale
Standard Deviation 17.1
|
60.5 units on a scale
Standard Deviation 18.8
|
Adverse Events
N-acetylcysteine
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
N-acetylcysteine
n=16 participants at risk
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.
|
Placebo
n=15 participants at risk
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.
|
|---|---|---|
|
Psychiatric disorders
Aggression
|
18.8%
3/16 • Twelve Weeks
|
13.3%
2/15 • Twelve Weeks
|
|
Musculoskeletal and connective tissue disorders
Accidental arm injury
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
General disorders
Appetite Increase
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Psychiatric disorders
Behavior Worse
|
6.2%
1/16 • Twelve Weeks
|
13.3%
2/15 • Twelve Weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cold
|
31.2%
5/16 • Twelve Weeks
|
33.3%
5/15 • Twelve Weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
2/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Psychiatric disorders
Difficulty Falling Asleep
|
25.0%
4/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Ear and labyrinth disorders
Ear Infection
|
12.5%
2/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
General disorders
Dry Mouth
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Hepatobiliary disorders
Elevated liver enzymes
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Gastrointestinal disorders
Encopresis
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Gastrointestinal disorders
Enuresis
|
6.2%
1/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Nervous system disorders
Hand Movements
|
0.00%
0/16 • Twelve Weeks
|
13.3%
2/15 • Twelve Weeks
|
|
General disorders
Fever
|
12.5%
2/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Nervous system disorders
Headache
|
18.8%
3/16 • Twelve Weeks
|
20.0%
3/15 • Twelve Weeks
|
|
Skin and subcutaneous tissue disorders
Hives
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Endocrine disorders
Hypoglycemia
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Vascular disorders
Increased Swelling of Feet
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Infections and infestations
Influenza
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Gastrointestinal disorders
Intermittent Dyspepsia
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Skin and subcutaneous tissue disorders
Itchy Skin
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Surgical and medical procedures
Nasal Cauterization
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Gastrointestinal disorders
Nausea
|
12.5%
2/16 • Twelve Weeks
|
20.0%
3/15 • Twelve Weeks
|
|
Skin and subcutaneous tissue disorders
Poison Ivy
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Skin and subcutaneous tissue disorders
Localized Rash
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Skin and subcutaneous tissue disorders
Scabies
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Psychiatric disorders
Skin Picking/SIB
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Nervous system disorders
Stuttering
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Endocrine disorders
Swollen neck lymph node of unknown origin
|
6.2%
1/16 • Twelve Weeks
|
0.00%
0/15 • Twelve Weeks
|
|
Psychiatric disorders
Threats to hurt self
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
Renal and urinary disorders
Urinary Tract Infection
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
|
General disorders
Weight Gain
|
0.00%
0/16 • Twelve Weeks
|
6.7%
1/15 • Twelve Weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place