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Treatment of Severe Childhood Aggression (The TOSCA Study)

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ClinicalTrials.gov Identifier: NCT00796302
Recruitment Status : Completed
First Posted : November 24, 2008
Results First Posted : April 20, 2016
Last Update Posted : July 26, 2017
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Michael Aman, Ohio State University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Attention Deficit Disorder With Hyperactivity
Interventions Drug: Methylphenidate HCl
Drug: Risperidone
Behavioral: Parent Management Training (PMT)
Drug: Placebo
Enrollment 168
Recruitment Details 256 participants were screened. 188 passed screening.
Pre-assignment Details Between initial contact and randomization, 108 potential participants were lost for the following reasons: 68 subjects failed screen criteria, 4 were ineligible at Baseline, 10 withdrew consent, 4 were lost to follow-up, and 2 were unable to swallow medication.
Arm/Group Title Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone)
Hide Arm/Group Description Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training. Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training.
Period Title: Overall Study
Started 84 84
Completed 71 66
Not Completed 13 18
Arm/Group Title Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone) Total
Hide Arm/Group Description Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training. Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training. Total of all reporting groups
Overall Number of Baseline Participants 84 84 168
Hide Baseline Analysis Population Description
ADHD & severe physical aggression
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 84 participants 168 participants
<=18 years
84
 100.0%
84
 100.0%
168
 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 84 participants 84 participants 168 participants
8.8  (1.98) 9.0  (2.05) 8.9  (2.01)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 84 participants 168 participants
Female
20
  23.8%
19
  22.6%
39
  23.2%
Male
64
  76.2%
65
  77.4%
129
  76.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 84 participants 84 participants 168 participants
84 84 168
1.Primary Outcome
Title NCBRF-TIQ D-Total Score
Hide Description

Parent ratings of aggression and hostility on the Nisonger Child Behavior Rating Form-Typical IQ (NCBRF-TIQ) D-Total Score. The NCBRF provides 1 prosocial subscale (Positive/Social) and 6 problem behavior subscales (Conduct Problem, Oppositional Behavior, Hyperactive, Inattentive, Overly Sensitive, and Withdrawn/Dysphoric). The NCBRF has excellent internal consistency, distinguishes between controls and subjects with DBDs. Conduct Problem and Oppositional Behavior subscales map closely to DSM-IV-TR symptoms of CD and ODD; they were scored together to form a variable called the D-Total.

For the NCBRF D-Total, higher scores reflect worse behavior. Each subscale is scored by taking the rating (0 [did not occur or was not a problem] to 3 [occurred a lot or was a very severe problem]) for all component items. The D-Total score was computed by adding the 6 scores from the Oppositional subscale and the 10 items from the Conduct Problem subscale. Thus D-Total scores could range from 0-69.

Time Frame Measured at baseline and Weeks 3, 4, 5, 6, 7, 8, 9
Hide Outcome Measure Data
Hide Analysis Population Description
ADHD & severe physical aggression
Arm/Group Title Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone)
Hide Arm/Group Description:
Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.
Children will receive active methylphenidate HCl and risperidone. Parents will receive parent management training
Overall Number of Participants Analyzed 84 84
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 43.5  (10.3) 42.1  (10.4)
Week 3 24.9  (15.3) 25.9  (15.2)
Week 4 22.4  (15.1) 17.1  (12.5)
Week 5 20.1  (15.7) 12.1  (10.1)
Week 6 20.7  (14.6) 13.8  (12.1)
Week 7 16.8  (12.8) 13.0  (11.2)
Week 8 17.8  (15.0) 11.7  (10.2)
Week 9 17.8  (15.4) 10.7  (9.0)
2.Other Pre-specified Outcome
Title Antisocial Behavior Scale - Reactive Aggression Subscale
Hide Description The Antisocial Behavior Scale (ABS) is a 28-item scale that contains 10 Proactive Aggression items and six Reactive Aggression items. Each item is rated on a 3-point scale, ranging from 1 (Never) to 3 (Very often). Thus, scores on the Reactive Aggression subscale can range from 6 through 18; with higher scores indicating more reactive aggression.
Time Frame Measured at baseline and Week 9
Hide Outcome Measure Data
Hide Analysis Population Description
ADHD & severe physical aggression
Arm/Group Title Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone)
Hide Arm/Group Description:
Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.
Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training.
Overall Number of Participants Analyzed 84 84
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 15.9  (1.8) 15.5  (2.4)
Week 9 12.3  (3.1) 11.0  (2.7)
3.Other Pre-specified Outcome
Title Clinical Global Impressions Scale for Improvement
Hide Description Using this clinician rating scale the patient's improvement is scored on a 7-point scale which ranges from “very much improved” (1), through “no change” (4), to “very much worse” (7). This scale was used at baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, & 9. Only endpoint (week 9 or subject's last visit) Clinical Global Impressions Scale for Improvement scores are reported below.
Time Frame Measured at endpoint visit
Hide Outcome Measure Data
Hide Analysis Population Description
ADHD & severe physical aggression; participants who completed a study endpoint visit and were given a Clinical Global Impressions Scale for Improvement rating
Arm/Group Title Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone)
Hide Arm/Group Description:
Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.
Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training.
Overall Number of Participants Analyzed 83 80
Measure Type: Number
Unit of Measure: participants
Much or very much improved at endpoint 58 63
Minimally improved at endpoint 22 11
Unchanged or worse at endpoint 3 6
4.Other Pre-specified Outcome
Title Clinical Global Impressions Scale for Severity of Illness
Hide Description Using this clinician rating scale the severity of the illness is scored from 1= normal to 7= extremely ill. This scale was used at baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, & 9. Only endpoint (week 9 or subject's last visit) Clinical Global Impressions Scale for Severity of Illness scores are reported below.
Time Frame Measured at endpoint visit
Hide Outcome Measure Data
Hide Analysis Population Description
ADHD and severe physical aggression; participants who completed a study endpoint visit and were given a Clinical Global Impressions Scale for Severity of Illness rating
Arm/Group Title Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone)
Hide Arm/Group Description:
Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.
Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training.
Overall Number of Participants Analyzed 83 78
Measure Type: Number
Unit of Measure: participants
Normal/Borderline/Mildly ill at endpoint 49 56
Moderately/Markedly/Severely ill at endpoint 34 22
Time Frame 9 weeks
Adverse Event Reporting Description Only adverse events for weeks 4 to 9 (when the second medication was used) are reported. After subtracting the 22 participants who were not given the second medication, AE data were available for 80 basic treatment and 73 augmented treatment participants.
 
Arm/Group Title Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone)
Hide Arm/Group Description Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training. Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training.
All-Cause Mortality
Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/80 (0.00%)   0/73 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Basic (Stimulant + PMT + Placebo) Augmented (Stimulant + PMT + Risperidone)
Affected / at Risk (%) Affected / at Risk (%)
Total   69/80 (86.25%)   62/73 (84.93%) 
Gastrointestinal disorders     
Diarrhea   9/80 (11.25%)  5/73 (6.85%) 
Gastrointestinal discomfort   4/80 (5.00%)  12/73 (16.44%) 
Vomiting   6/80 (7.50%)  10/73 (13.70%) 
General disorders     
Trouble falling asleep   29/80 (36.25%)  14/73 (19.18%) 
Sedation   20/80 (25.00%)  16/73 (21.92%) 
Headache   17/80 (21.25%)  16/73 (21.92%) 
Metabolism and nutrition disorders     
Appetite decrease   19/80 (23.75%)  9/73 (12.33%) 
Appetite increase   7/80 (8.75%)  10/73 (13.70%) 
Respiratory, thoracic and mediastinal disorders     
Rhinorrhea   14/80 (17.50%)  11/73 (15.07%) 
Cough   20/80 (25.00%)  14/73 (19.18%) 
Indicates events were collected by systematic assessment
These results were obtained with children selected for severity of aggression and disruptive behavior, and the risk-benefit ratio may well be decreased for children with milder disruptive behavior or no physical aggression.
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: Michael Aman
Organization: Ohio State University
Phone: 614-688-4196
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael Aman, Ohio State University
ClinicalTrials.gov Identifier: NCT00796302     History of Changes
Other Study ID Numbers: R01MH077907 ( U.S. NIH Grant/Contract )
DSIR 84-CTS
1R01MH077907-01A2 ( U.S. NIH Grant/Contract )
1R01MH077676-01A2 ( U.S. NIH Grant/Contract )
1R01MH077750-01A2 ( U.S. NIH Grant/Contract )
1R01MH077997-01A2 ( U.S. NIH Grant/Contract )
First Submitted: November 21, 2008
First Posted: November 24, 2008
Results First Submitted: February 18, 2016
Results First Posted: April 20, 2016
Last Update Posted: July 26, 2017