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Atomoxetine, Placebo and Parent Management Training in Autism (Strattera)

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ClinicalTrials.gov Identifier: NCT00844753
Recruitment Status : Completed
First Posted : February 16, 2009
Results First Posted : February 4, 2016
Last Update Posted : February 4, 2016
Sponsor:
Collaborators:
University of Pittsburgh
Ohio State University
Information provided by (Responsible Party):
tristram smith, University of Rochester

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Autism
Pervasive Development Disorder
Asperger's Disorder
Attention Deficit Hyperactivity Disorder
Interventions Drug: atomoxetine
Drug: Placebo
Behavioral: Parent Management Training
Enrollment 128
Recruitment Details 200 participants were screened. 131 passed screening. Participants failed screening for the following reasons: 16 Attention Deficit Hyperactivity Disorder (ADHD) not confirmed, 23 Autism Spectrum Disorder not confirmed, 7 previous parent therapy or mental age too low, 23 for other reasons.
Pre-assignment Details Two participants who passed screening withdrew and one child became ineligible because of ADHD severity declining at baseline.
Arm/Group Title Atomoxetine (ATX) + Parent Management Training Atomoxetine (ATX) Without Parent Management Training Placebo + Parent Management Training Placebo Without Parent Management Training
Hide Arm/Group Description

ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to adverse events. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.

Parent Management Training (PT)-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.

ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.

Sugar pill administered twice daily

Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.

Sugar pill administered twice daily.
Period Title: Overall Study
Started 32 32 32 32
Completed 24 29 25 21
Not Completed 8 3 7 11
Reason Not Completed
Lack of Efficacy             1             0             2             2
Adverse Event             3             2             5             5
Lost to Follow-up             1             1             0             1
could not swallow medication             2             0             0             0
Withdrawal by Subject             1             0             0             3
Arm/Group Title Atomoxetine + Parent Management Training Atomoxetine Without Parent Management Training Placebo + Parent Management Training Placebo Without Parent Management Training Total
Hide Arm/Group Description

ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.

Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.

ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.

Sugar pill administered twice daily

Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.

Sugar pill administered twice daily. Total of all reporting groups
Overall Number of Baseline Participants 32 32 32 32 128
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 32 participants 32 participants 32 participants 128 participants
8.0  (1.9) 8.6  (2.3) 7.7  (1.5) 8.2  (2.4) 8.1  (2.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 32 participants 32 participants 32 participants 128 participants
Female
1
   3.1%
6
  18.8%
5
  15.6%
8
  25.0%
20
  15.6%
Male
31
  96.9%
26
  81.3%
27
  84.4%
24
  75.0%
108
  84.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 32 participants 32 participants 32 participants 32 participants 128 participants
32 32 32 32 128
1.Primary Outcome
Title Percentage of Participants Who Were Attention Deficit Hyperactivity Disorder (ADHD) Respondents
Hide Description Respondents were defined as having ≥30% decrease on the SNAP and CGI-I<=2). The Swanson, Nolan, and Pelham (SNAP)–IV Parent and Teacher Rating Scales were used to measure ADHD and oppositional symptoms at home and school. The SNAP-IV ADHD section contains items for each of the 18 Diagnostic and Statistical Manual of Mental Disorders-IV symptoms of ADHD rated from 0 (not at all) to 3 (very much). The Clinical Global Impressions Scale (CGI) includes subscales for severity of illness and global improvement. The Severity scale is scored from 1 (normal) to 7 (extremely ill), with a rating of ≥4 required for inclusion. The Improvement score ranged from 1 (very much improved) through 4 (no change) to 7 (very much worse). The CGI was completed by a blinded rater based on parent/child interview and review of completed parent and school behavior problem questionnaires at each study visit.
Time Frame week 10
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atomoxetine + Parent Management Training Atomoxetine Without Parent Management Training Placebo + Parent Management Training Placebo Without Parent Management Training
Hide Arm/Group Description:

ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.

Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.

ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.

Sugar pill administered twice daily

Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.

Sugar pill administered twice daily.
Overall Number of Participants Analyzed 32 32 32 32
Measure Type: Number
Unit of Measure: percentage of participants
45.2 46.9 29.0 19.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atomoxetine + Parent Management Training, Atomoxetine Without Parent Management Training, Placebo + Parent Management Training, Placebo Without Parent Management Training
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Who Were Autism Spectrum Disorder Respondents
Hide Description

Respondents were defined as having ≥30% decrease on the HSQ and CGI-I≤2). The 25-item HSQ was adapted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate behavioral noncompliance in children with autism spectrum disorder (ASD). The Home Situations Questionnaire – Pervasive Developmental Disorder (HSQ) is a 25-item parent rating scale assessing noncompliance. Parents are asked to indicate whether each item is a problem and, if so, its severity from 1 (mild) to 9 (severe). The School Situations Questionnaire (SSQ) is a 9-item teacher rating scale that assesses noncompliance. The SSQ is a companion instrument to the HSQ and uses the same rating scale.

The Clinical Global Impressions Scale (CGI) includes subscales for severity of illness and global improvement. The Severity scale is scored from 1 (normal) to 7 (extremely ill),

Time Frame week 10
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atomoxetine + Parent Management Training Atomoxetine Without Parent Management Training Placebo + Parent Management Training Placebo Without Parent Management Training
Hide Arm/Group Description:

ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.

Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.

ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.

Sugar pill administered twice daily

Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.

Sugar pill administered twice daily.
Overall Number of Participants Analyzed 32 32 32 32
Measure Type: Number
Unit of Measure: percentage of participants
22.6 43.8 38.7 16.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atomoxetine + Parent Management Training, Atomoxetine Without Parent Management Training, Placebo + Parent Management Training, Placebo Without Parent Management Training
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.95
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Time Frame 10 weeks
Adverse Event Reporting Description Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
 
Arm/Group Title Atomoxetine Placebo
Hide Arm/Group Description Data includes both the ATX alone arm and the ATX+ parent therapy arm Data includes the placebo alone arm and the placebo+parent therapy arm
All-Cause Mortality
Atomoxetine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Atomoxetine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/63 (0.00%)   0/62 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Atomoxetine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   59/63 (93.65%)   61/62 (98.39%) 
Gastrointestinal disorders     
Vomiting   14/63 (22.22%)  10/62 (16.13%) 
Constipation   7/63 (11.11%)  9/62 (14.52%) 
Abdominal pain   10/63 (15.87%)  3/62 (4.84%) 
Diarrhea   3/63 (4.76%)  4/62 (6.45%) 
General disorders     
Difficulty sleeping   19/63 (30.16%)  11/62 (17.74%) 
Metabolism and nutrition disorders     
Decreased Appetite   30/63 (47.62%)  18/62 (29.03%) 
Psychiatric disorders     
Irritability   27/63 (42.86%)  29/62 (46.77%) 
Agitation   19/63 (30.16%)  20/62 (32.26%) 
Aggression   2/63 (3.17%)  4/62 (6.45%) 
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
Name/Title: Ben Handen
Organization: University of Pittsburgh
Phone: 412-235-5452
Publications of Results:
Barkley, R. A., & Edelbrock, C. (1987). Assessing situational variation in children's problem behaviors: The Home and School Situations Questionnaires. In R. Prinz (Ed.), Advances in behavioral assessment of children and families (pp. 157-176). Greenwich, CT: JAI Press Inc
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: tristram smith, University of Rochester
ClinicalTrials.gov Identifier: NCT00844753     History of Changes
Obsolete Identifiers: NCT00699205
Other Study ID Numbers: 1R01MH079082-01A2 ( U.S. NIH Grant/Contract )
First Submitted: June 6, 2008
First Posted: February 16, 2009
Results First Submitted: November 23, 2015
Results First Posted: February 4, 2016
Last Update Posted: February 4, 2016