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Trial record 11 of 53 for:    Developmental Disabilities | ( Map: Indiana, United States )

Evaluating the Effectiveness of Aripiprazole and D-Cycloserine to Treat Symptoms Associated With Autism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00198107
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : March 29, 2019
Last Update Posted : April 9, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Indiana University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Autistic Disorder
Interventions Drug: Aripiprazole
Drug: Placebo
Drug: D-cycloserine
Enrollment 81
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Period Title: Double-Blind Period
Started 41 40 0
1 or More Follow-up Visits 40 38 0
Completed 35 37 0
Not Completed 6 3 0
Reason Not Completed
Adverse Event             1             1             0
Lack of Efficacy             2             0             0
Lost to Follow-up             2             1             0
Physician Decision             1             0             0
Withdrawal by Subject             0             1             0
Period Title: Pilot Add-On Aripiprazole +D-cycloserine
Started 0 0 10
Completed 0 0 8
Not Completed 0 0 2
Reason Not Completed
Withdrawal by Subject             0             0             2
Arm/Group Title 1 Placebo 2 Aripiprazole Total
Hide Arm/Group Description

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Total of all reporting groups
Overall Number of Baseline Participants 41 40 81
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 40 participants 81 participants
<=18 years
41
 100.0%
40
 100.0%
81
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 40 participants 81 participants
9.4  (3.5) 9.0  (2.9) 9.2  (3.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 40 participants 81 participants
Female
7
  17.1%
4
  10.0%
11
  13.6%
Male
34
  82.9%
36
  90.0%
70
  86.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 41 participants 40 participants 81 participants
41
 100.0%
40
 100.0%
81
 100.0%
1.Primary Outcome
Title Mean Post-baseline Aberrant Behavior Checklist Irritability Score, Parent Report, Double-blind Phase
Hide Description The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its subscales is that higher scores, indicate greater severity. Fifteen item scores with values ranging from 0 (not a problem) to 3 (problem is severe) are summed to arrive at the total irritability scale store ranging from 0 to 45. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting
Time Frame Weeks 1, 2, 3, 4, 6, and 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants with at least one post-baseline ABC score. One participant assigned to placebo and 2 participants assigned to aripiprazole had no post-baseline assessments.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 40 38 0
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
25.5
(22.8 to 28.3)
18.6
(15.8 to 21.4)
2.Primary Outcome
Title Odds of Improvement as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)
Hide Description Clinical Global Impressions (Guy, 1976) global 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, with lower scores indicating greater improvement (1=very much improved and 2=much improved). Participants with a CGI-I score of 1 or 2 were classified as improved. Odds were estimated using a repeated measures logistic regression model with treatment group, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average log odds across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes.
Time Frame Weeks 1, 2, 3, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants with at least one post-baseline CGI-I rating. One participant assigned to placebo and 2 participants assigned to aripiprazole had no post-baseline ratings.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 40 38 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: odds
0.10
(0.05 to 0.23)
0.50
(0.31 to 0.79)
3.Secondary Outcome
Title Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Score, Parent Report, Double-blind Phase
Hide Description The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item Parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers overactivity, impulsiveness, inattention and noncompliance. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its subscale is that higher scores, indicate greater severity. Sixteen item scores with values ranging from 0 (not a problem) to 3 (problem is severe) are summed to arrive at the total score ranging from 0 to 48. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average across study timepoints.
Time Frame Weeks 1, 2, 3, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants with at least one post-baseline ABC score. One participant assigned to placebo and 2 participants assigned to aripiprazole had no post-baseline assessments.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 40 38 0
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
29.7
(26.8 to 32.5)
22.5
(19.6 to 25.4)
4.Secondary Outcome
Title Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Score, Parent Report, Double-blind Phase
Hide Description The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item Parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its subscales is that higher scores, indicate greater severity. Four item scores with values ranging from 0 (not a problem) to 3 (problem is severe) are summed to arrive at the total inappropriate speech scale score ranging from 0 to 12. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average across study timepoints.
Time Frame Weeks 1, 2, 3, 4, 6, and 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants with at least one post-baseline ABC score. One participant assigned to placebo and 2 participants assigned to aripiprazole had no post-baseline assessments.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 40 38 0
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
7.4
(6.7 to 8.1)
5.0
(4.2 to 5.7)
5.Secondary Outcome
Title Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Score, Parent Report, Double-blind Phase
Hide Description The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item Parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its subscales is that higher scores, indicates greater severity. Sixteen item scores with values ranging from 0 (not a problem) to 3 (problem is severe) are summed to arrive at the total social withdrawal scale score ranging from 0 to 48. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average across study timepoints.
Time Frame Weeks 1, 2, 3, 4, 6, and 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants with at least one post-baseline ABC score. One participant assigned to placebo and 2 participants assigned to aripiprazole had no post-baseline assessments.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 40 38 0
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
15.4
(13.4 to 17.5)
11.7
(9.6 to 13.7)
6.Secondary Outcome
Title Mean Post-baseline Aberrant Behavior Checklist Stereotypy Score, Parent Report, Double-blind Phase
Hide Description The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item Parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its subscales is that higher scores, indicates greater severity. Seven item scores with values ranging from 0 (not a problem) to 3 (problem is severe) are summed to arrive at the total stereotypy scale score ranging from 0 to 21. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average across study timepoints.
Time Frame Weeks 1, 2, 3, 4, 6, and 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants with at least one post-baseline ABC score. One participant assigned to placebo and 2 participants assigned to aripiprazole had no post-baseline assessments.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 40 38 0
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
10.0
(8.9 to 11.1)
7.2
(6.0 to 8.3)
7.Secondary Outcome
Title Mean Post-baseline Score on a Modified Version of the Compulsion Subscale of the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)
Hide Description The CYBOCS- PDD is a semi-structured clinician-rated scale designed to rate the current severity of repetitive behavior in children with idiopathic autism spectrum disorders. Once the current repetitive behaviors are identified, they are rated on: Time Spent, Interference, Distress, Resistance, and Control. Each of these items is scored from 0 (least symptomatic) to 4 (most symptomatic), yielding a Total score from 0 to 20. Higher scores indicate higher severity. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average across study timepoints.
Time Frame Weeks 2, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants with at least one post-baseline CY-BOCS score. Two participants assigned to placebo and 2 participants assigned to aripiprazole had no post-baseline assessments.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 39 38 0
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
14.4
(13.4 to 15.5)
12.5
(11.5 to 13.5)
8.Secondary Outcome
Title Mean Vineland Maladaptive Behavior Subscales Total Score, Week 8
Hide Description The Vineland Adaptive Behavior Scales, (Survey Interview Form) is a measure of adaptive behavior in children, adolescents and adults. It yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning. An increase in standard scores from Baseline to the Final Visit indicates improvement. Means were estimated using a repeated measures linear regression model with treatment group, study week (in categories, baseline or 8 weeks), and sex x Tanner stage stratum as covariates.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants. For 7 participants who exited the double-blind phase prior to week 8 but completed an exit interview (all assigned to placebo), week 8 scores were imputed using a last observation carried forward approach.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 41 40 0
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
33.1
(29.6 to 36.6)
23.1
(19.6 to 26.5)
9.Secondary Outcome
Title Mean Autism Diagnostic Observation Schedule (ADOS) Social Affect and Restricted and Repetitive Behaviors Total Score, Week 8
Hide Description Autism Diagnostic Observation Scale (ADOS) (Lord), Modules 1-3 yields scores in 2 scales: Social Affect and Restricted and Repetitive Behavior. The ADOS has been repeatedly evaluated as a diagnostic measure, it has also been used as an outcome measure of autism severity (Aldred et al., 2004; Gutstein, 2007; Owly et al, 2001, Green et al, 2010). For modules 1-3, scores ranging from 0-2 on 14 items are summed to arrive at the Social Affect and Restricted and Repetitive Behavior Total Score, which ranges from 0 to 28. Higher scores indicate greater autism severity. Means were estimated using a repeated measures linear regression model with treatment group, study week (in categories, baseline or 8 weeks), and sex x Tanner stage stratum as covariates
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants. For 9 participants who exited the double-blind phase prior to week 8 but completed an exit interview (8 assigned to placebo and 1 to aripiprazole), week 8 scores were imputed using a last observation carried forward approach.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 41 40 0
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
19.0
(17.6 to 20.4)
18.3
(17.0 to 19.7)
10.Secondary Outcome
Title Mean Social Reciprocity Scale (SRS) Total Score, Week 8
Hide Description The 65-item SRS is a standardized measure of the core symptoms of autism. Each item is scored on a 4-point Likert scale. The score of each individual item is summed to create a total raw score. A total score results are as follows: 0-62: Within normal limits 63-79: Mild range of impairment 80-108: Moderate range of impairment 109-149: Severe range of impairment. Means were estimated using a repeated measures linear regression model with treatment group, study week (in categories, baseline or 8 weeks), and sex x Tanner stage stratum as covariates.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized study participants. For 9 participants who exited the double-blind phase prior to week 8 but completed an exit interview (8 assigned to placebo and 1 to aripiprazole), week 8 scores were imputed using a last observation carried forward approach.
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Hide Arm/Group Description:

Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

Overall Number of Participants Analyzed 41 40 0
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
127.6
(119.8 to 135.3)
112.6
(104.8 to 120.3)
Time Frame Eight weeks or at the time of latest data collection.
Adverse Event Reporting Description Adverse event information was collected via a structured side effect rating scale completed with the participant and their primary caregiver. This included a list of side-effects that have been reported with aripiprazole at a rate greater than 1%. The physician also asked about any visits to the doctor, new medication use, or any other complaints. Events that were not present at baseline and occurred or worsened after the date of randomization are reported.
 
Arm/Group Title 1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
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Participants will take placebo

Placebo: Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

Participants will take aripiprazole

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Participants first will take aripiprazole then will also take D-cycloserine

Aripiprazole: Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

D-cycloserine: D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

All-Cause Mortality
1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/40 (0.00%)   0/40 (0.00%)   0/10 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/40 (0.00%)   0/40 (0.00%)   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
1 Placebo 2 Aripiprazole 3 Aripiprazole + D-cycloserine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   35/40 (87.50%)   40/40 (100.00%)   10/10 (100.00%) 
Gastrointestinal disorders       
Change in Stool   2/40 (5.00%)  2/40 (5.00%)  0/10 (0.00%) 
Constipation   4/40 (10.00%)  8/40 (20.00%)  0/10 (0.00%) 
Diarrhea   3/40 (7.50%)  7/40 (17.50%)  5/10 (50.00%) 
Nausea   0/40 (0.00%)  2/40 (5.00%)  0/10 (0.00%) 
Stomach or abdominal discomfort   4/40 (10.00%)  7/40 (17.50%)  2/10 (20.00%) 
Vomiting   8/40 (20.00%)  15/40 (37.50%)  3/10 (30.00%) 
General disorders       
Dry mouth   2/40 (5.00%)  2/40 (5.00%)  0/10 (0.00%) 
Hypersalivation   3/40 (7.50%)  3/40 (7.50%)  1/10 (10.00%) 
Appetite decrease   6/40 (15.00%)  12/40 (30.00%)  1/10 (10.00%) 
Appetite increase   11/40 (27.50%)  16/40 (40.00%)  3/10 (30.00%) 
Sedation/Drowsiness   3/40 (7.50%)  5/40 (12.50%)  0/10 (0.00%) 
Tiredness/fatigue   10/40 (25.00%)  21/40 (52.50%)  2/10 (20.00%) 
Fever   2/40 (5.00%)  3/40 (7.50%)  0/10 (0.00%) 
Infections and infestations       
Flu or upper respiratory problems   3/40 (7.50%)  3/40 (7.50%)  1/10 (10.00%) 
Nasal congestion or Cold   16/40 (40.00%)  16/40 (40.00%)  1/10 (10.00%) 
Metabolism and nutrition disorders       
Weight gain   5/40 (12.50%)  8/40 (20.00%)  0/10 (0.00%) 
Weight loss   5/40 (12.50%)  4/40 (10.00%)  1/10 (10.00%) 
Nervous system disorders       
Headache   8/40 (20.00%)  3/40 (7.50%)  1/10 (10.00%) 
Muscle rigidity   0/40 (0.00%)  3/40 (7.50%)  0/10 (0.00%) 
Tremor   0/40 (0.00%)  3/40 (7.50%)  0/10 (0.00%) 
Psychiatric disorders       
Anxiety/Nervousness/Worry   0/40 (0.00%)  3/40 (7.50%)  1/10 (10.00%) 
Change in speech   7/40 (17.50%)  3/40 (7.50%)  2/10 (20.00%) 
Difficulty falling asleep   6/40 (15.00%)  3/40 (7.50%)  0/10 (0.00%) 
Increased motor activity   5/40 (12.50%)  3/40 (7.50%)  2/10 (20.00%) 
Increased repetitive speech   2/40 (5.00%)  3/40 (7.50%)  1/10 (10.00%) 
Interrupted sleep/other sleep problems   8/40 (20.00%)  4/40 (10.00%)  1/10 (10.00%) 
Irritability   7/40 (17.50%)  3/40 (7.50%)  2/10 (20.00%) 
Restlessness/Agitation, including fidgety   2/40 (5.00%)  3/40 (7.50%)  2/10 (20.00%) 
Sadness   0/40 (0.00%)  3/40 (7.50%)  0/10 (0.00%) 
Self-Injurious Behavior   1/40 (2.50%)  3/40 (7.50%)  0/10 (0.00%) 
Stereotypy   8/40 (20.00%)  3/40 (7.50%)  2/10 (20.00%) 
Hypertalkativeness   0/40 (0.00%)  0/40 (0.00%)  1/10 (10.00%) 
Renal and urinary disorders       
Enuresis   2/40 (5.00%)  3/40 (7.50%)  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough   4/40 (10.00%)  3/40 (7.50%)  2/10 (20.00%) 
Skin and subcutaneous tissue disorders       
Localized rash   3/40 (7.50%)  3/40 (7.50%)  0/10 (0.00%) 
Vascular disorders       
Dizziness/faintness   0/40 (0.00%)  4/40 (10.00%)  1/10 (10.00%) 
Intermittent nosebleed   0/40 (0.00%)  3/40 (7.50%)  0/10 (0.00%) 
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Christopher J. McDougle, MD
Organization: Indiana University
Phone: 781-860-1783
EMail: cmcdougle@partners.org
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Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00198107     History of Changes
Other Study ID Numbers: R01MH072961 ( U.S. NIH Grant/Contract )
R01MH072961 ( U.S. NIH Grant/Contract )
DSIR 82-SEDR
First Submitted: September 12, 2005
First Posted: September 20, 2005
Results First Submitted: April 30, 2018
Results First Posted: March 29, 2019
Last Update Posted: April 9, 2019