Trial Outcomes & Findings for Treatment of Severe Childhood Aggression (The TOSCA Study) (NCT NCT00796302)

Last Updated: 2017-07-26

Results Overview

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6 problem behavior subscales (Conduct Problem, Oppositional Behavior, Hyperactive, Inattentive, Overly Sensitive, and Withdrawn/Dysphoric).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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

168 participants

Primary outcome timeframe

Measured at baseline and Weeks 3, 4, 5, 6, 7, 8, 9

Results posted on

2017-07-26

Participant Flow

256 participants were screened. 188 passed screening.

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.

Participant milestones

Participant milestones
Measure	Basic (Stimulant + PMT + Placebo) Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.	Augmented (Stimulant + PMT + Risperidone) Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training.
Overall Study STARTED	84	84
Overall Study COMPLETED	71	66
Overall Study NOT COMPLETED	13	18

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment of Severe Childhood Aggression (The TOSCA Study)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Basic (Stimulant + PMT + Placebo) n=84 Participants Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.	Augmented (Stimulant + PMT + Risperidone) n=84 Participants Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training.	Total n=168 Participants Total of all reporting groups
Age, Categorical <=18 years	84 Participants n=5 Participants	84 Participants n=7 Participants	168 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	8.8 years STANDARD_DEVIATION 1.98 • n=5 Participants	9.0 years STANDARD_DEVIATION 2.05 • n=7 Participants	8.9 years STANDARD_DEVIATION 2.01 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	64 Participants n=5 Participants	65 Participants n=7 Participants	129 Participants n=5 Participants
Region of Enrollment United States	84 participants n=5 Participants	84 participants n=7 Participants	168 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured at baseline and Weeks 3, 4, 5, 6, 7, 8, 9

Population: ADHD \& severe physical aggression

Outcome measures

Outcome measures
Measure	Basic (Stimulant + PMT + Placebo) n=84 Participants Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.	Augmented (Stimulant + PMT + Risperidone) n=84 Participants Children will receive active methylphenidate HCl and risperidone. Parents will receive parent management training
NCBRF-TIQ D-Total Score Baseline	43.5 units on a scale Standard Deviation 10.3	42.1 units on a scale Standard Deviation 10.4
NCBRF-TIQ D-Total Score Week 3	24.9 units on a scale Standard Deviation 15.3	25.9 units on a scale Standard Deviation 15.2
NCBRF-TIQ D-Total Score Week 4	22.4 units on a scale Standard Deviation 15.1	17.1 units on a scale Standard Deviation 12.5
NCBRF-TIQ D-Total Score Week 5	20.1 units on a scale Standard Deviation 15.7	12.1 units on a scale Standard Deviation 10.1
NCBRF-TIQ D-Total Score Week 6	20.7 units on a scale Standard Deviation 14.6	13.8 units on a scale Standard Deviation 12.1
NCBRF-TIQ D-Total Score Week 7	16.8 units on a scale Standard Deviation 12.8	13.0 units on a scale Standard Deviation 11.2
NCBRF-TIQ D-Total Score Week 8	17.8 units on a scale Standard Deviation 15.0	11.7 units on a scale Standard Deviation 10.2
NCBRF-TIQ D-Total Score Week 9	17.8 units on a scale Standard Deviation 15.4	10.7 units on a scale Standard Deviation 9.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Measured at baseline and Week 9

Population: ADHD \& severe physical aggression

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.

Outcome measures

Outcome measures
Measure	Basic (Stimulant + PMT + Placebo) n=84 Participants Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.	Augmented (Stimulant + PMT + Risperidone) n=84 Participants Children will receive active methylphenidate HCl and risperidone. Parents will receive parent management training
Antisocial Behavior Scale - Reactive Aggression Subscale Baseline	15.9 units on a scale Standard Deviation 1.8	15.5 units on a scale Standard Deviation 2.4
Antisocial Behavior Scale - Reactive Aggression Subscale Week 9	12.3 units on a scale Standard Deviation 3.1	11.0 units on a scale Standard Deviation 2.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Measured at endpoint visit

Population: ADHD \& severe physical aggression; participants who completed a study endpoint visit and were given a Clinical Global Impressions Scale for Improvement rating

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.

Outcome measures

Outcome measures
Measure	Basic (Stimulant + PMT + Placebo) n=83 Participants Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.	Augmented (Stimulant + PMT + Risperidone) n=80 Participants Children will receive active methylphenidate HCl and risperidone. Parents will receive parent management training
Clinical Global Impressions Scale for Improvement Minimally improved at endpoint	22 participants	11 participants
Clinical Global Impressions Scale for Improvement Much or very much improved at endpoint	58 participants	63 participants
Clinical Global Impressions Scale for Improvement Unchanged or worse at endpoint	3 participants	6 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Measured at endpoint visit

Population: 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

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.

Outcome measures

Outcome measures
Measure	Basic (Stimulant + PMT + Placebo) n=83 Participants Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.	Augmented (Stimulant + PMT + Risperidone) n=78 Participants Children will receive active methylphenidate HCl and risperidone. Parents will receive parent management training
Clinical Global Impressions Scale for Severity of Illness Normal/Borderline/Mildly ill at endpoint	49 participants	56 participants
Clinical Global Impressions Scale for Severity of Illness Moderately/Markedly/Severely ill at endpoint	34 participants	22 participants

Adverse Events

Basic (Stimulant + PMT + Placebo)

Serious events: 0 serious events

Other events: 69 other events

Deaths: 0 deaths

Augmented (Stimulant + PMT + Risperidone)

Serious events: 0 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Basic (Stimulant + PMT + Placebo) n=80 participants at risk Children will receive active methylphenidate HCl and placebo. Parents will receive parent management training.	Augmented (Stimulant + PMT + Risperidone) n=73 participants at risk Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training.
General disorders Trouble falling asleep	36.2% 29/80 • 9 weeks 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.	19.2% 14/73 • 9 weeks 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.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	17.5% 14/80 • 9 weeks 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.	15.1% 11/73 • 9 weeks 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.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 20/80 • 9 weeks 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.	19.2% 14/73 • 9 weeks 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.
Metabolism and nutrition disorders Appetite decrease	23.8% 19/80 • 9 weeks 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.	12.3% 9/73 • 9 weeks 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.
Metabolism and nutrition disorders Appetite increase	8.8% 7/80 • 9 weeks 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.	13.7% 10/73 • 9 weeks 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.
Gastrointestinal disorders Diarrhea	11.2% 9/80 • 9 weeks 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.	6.8% 5/73 • 9 weeks 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.
Gastrointestinal disorders Gastrointestinal discomfort	5.0% 4/80 • 9 weeks 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.	16.4% 12/73 • 9 weeks 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.
Gastrointestinal disorders Vomiting	7.5% 6/80 • 9 weeks 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.	13.7% 10/73 • 9 weeks 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.
General disorders Sedation	25.0% 20/80 • 9 weeks 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.	21.9% 16/73 • 9 weeks 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.
General disorders Headache	21.2% 17/80 • 9 weeks 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.	21.9% 16/73 • 9 weeks 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.

Additional Information

Michael Aman

Ohio State University

Phone: 614-688-4196

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place