Treatment of Severe Childhood Aggression (The TOSCA Study)
NCT ID: NCT00796302
Last Updated: 2017-07-26
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE4
168 participants
INTERVENTIONAL
2008-08-31
2012-11-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Risperidone Augmentation for Treatment-Resistant Aggression in ADHD
NCT00297739
Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study)
NCT00794625
Treatment of Impulsive Aggression (IA) in Adolescent With ADHD in Conjunction With Standard ADHD Treatment
NCT03597503
Predictors of Improvements in Irritability and Aggression in Children With ADHD Treated With CNS Stimulants
NCT06871488
Methylphenidate for Treating Children With ADHD and Tourette Syndrome
NCT00441649
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
For the next 3 weeks, all child participants will take methylphenidate HCl at a dose that will start low and gradually be increased until the most effective dose is determined. For the next 6 weeks, child participants will add either risperidone or a placebo to their regimen of methylphenidate HCl. This second medication will also be started at a low dose and raised to appropriate levels of tolerability. During the 9 weeks of medication adjustment, participants will attend weekly study visits to complete questionnaires and have their vital signs measured. Parents will attend education sessions at each of these visits. The child's teacher will also fill out weekly questionnaires on the child's behavior. Every 3 weeks, child participants will be tested on verbal memory, attention, and impulsiveness. After the 9-week period, child participants will again undergo a physical exam, lab tests, and an ECG.
At this point, if the child's behavior has improved, the child will continue the same treatment for the next 3 months. Monthly study visits will include parent education sessions and recording of parent and teacher evaluations of the child. All participants will attend a 1-year follow-up visit that will include previous assessments.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
1
Children will receive active methylphenidate HCl and active risperidone. Parents will receive parent management training.
Methylphenidate HCl
For children weighing less than 25 kg, the dose will be titrated at 18 mg for the first 7 days, 36 mg for the next 4 days, and, if needed, 54 mg for the next 4 days. For children weighing more than 25 kg, the dose will be titrated at 18 mg for the first 4 days, 36 mg for the next 3 days, 54 mg for the next 4 days, and 72 mg for the next 3 days.
Once the child's optimal dose is established, he or she will continue on that dose for the rest of the 21-week trial.
One pill is taken once daily.
Risperidone
For children weighing less than 45 kg, the dose will start at 0.5 mg at night. After 4 days, the child's dose may be increased to 1 mg a day. On Day 8, the child's dose may be increased to 1.5 mg a day. On Day 16, the child's dose may be increased to 2.0 mg a day. On Day 22, the child's dose may be increased to 2.5 mg a day.
For children weighing more than 45 kg, the dose will start at 0.5 mg at night. After 4 days, the child's dose may be increased to 1.0 mg a day. On Day 8, the child's dose may be increased to 1.5 mg a day. On Day 12, the child's dose may be increased to 2.0 mg a day. On Day 15, the child's dose may be increased to 2.5 mg a day. On Day 18, the child's dose may be increased to 3 mg a day. On Day 23, the child's dose may be increased to 3.5 mg a day.
Parent Management Training (PMT)
PMT will include individual parent sessions held weekly for 9 weeks, with two booster sessions to be completed during the 3-month extension. Sessions will include development of problem-solving skills and behavior management strategies, practice activities, and role-playing with the behavioral therapist.
2
Children will receive methylphenidate HCl and placebo instead of the active risperidone. Parents will receive parent management training.
Methylphenidate HCl
For children weighing less than 25 kg, the dose will be titrated at 18 mg for the first 7 days, 36 mg for the next 4 days, and, if needed, 54 mg for the next 4 days. For children weighing more than 25 kg, the dose will be titrated at 18 mg for the first 4 days, 36 mg for the next 3 days, 54 mg for the next 4 days, and 72 mg for the next 3 days.
Once the child's optimal dose is established, he or she will continue on that dose for the rest of the 21-week trial.
One pill is taken once daily.
Parent Management Training (PMT)
PMT will include individual parent sessions held weekly for 9 weeks, with two booster sessions to be completed during the 3-month extension. Sessions will include development of problem-solving skills and behavior management strategies, practice activities, and role-playing with the behavioral therapist.
Placebo
One pill will be taken once daily for the first 4 days and then twice daily until Week 21.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Methylphenidate HCl
For children weighing less than 25 kg, the dose will be titrated at 18 mg for the first 7 days, 36 mg for the next 4 days, and, if needed, 54 mg for the next 4 days. For children weighing more than 25 kg, the dose will be titrated at 18 mg for the first 4 days, 36 mg for the next 3 days, 54 mg for the next 4 days, and 72 mg for the next 3 days.
Once the child's optimal dose is established, he or she will continue on that dose for the rest of the 21-week trial.
One pill is taken once daily.
Risperidone
For children weighing less than 45 kg, the dose will start at 0.5 mg at night. After 4 days, the child's dose may be increased to 1 mg a day. On Day 8, the child's dose may be increased to 1.5 mg a day. On Day 16, the child's dose may be increased to 2.0 mg a day. On Day 22, the child's dose may be increased to 2.5 mg a day.
For children weighing more than 45 kg, the dose will start at 0.5 mg at night. After 4 days, the child's dose may be increased to 1.0 mg a day. On Day 8, the child's dose may be increased to 1.5 mg a day. On Day 12, the child's dose may be increased to 2.0 mg a day. On Day 15, the child's dose may be increased to 2.5 mg a day. On Day 18, the child's dose may be increased to 3 mg a day. On Day 23, the child's dose may be increased to 3.5 mg a day.
Parent Management Training (PMT)
PMT will include individual parent sessions held weekly for 9 weeks, with two booster sessions to be completed during the 3-month extension. Sessions will include development of problem-solving skills and behavior management strategies, practice activities, and role-playing with the behavioral therapist.
Placebo
One pill will be taken once daily for the first 4 days and then twice daily until Week 21.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* DSM-IV diagnosis of a disruptive behavior disorder, including CD or ODD
* Evidence of serious physical aggression, as rated on the Overt Aggression Scale-Modified, and as determined by parent or guardian ratings on the NCBRF D-Total Score. In addition, the blinded clinician must assign a clinical global impressions severity score of 4 or greater for aggression.
* Prior to random assignment, participants must be free of all psychotropic medicines for 2 weeks for most drugs (such as most antidepressants, alpha agonists, beta blockers, anxiolytics, mood stabilizers, and antihistamines), and 4 weeks for depot antipsychotics and fluoxetine.
Exclusion Criteria
* Pregnancy or a history of seizure disorder or other neurological or medical disorders for which medication may present a considerable risk
* Abnormal liver function
* Pervasive developmental disorder, schizophrenia or other psychotic disorders, or eating disorders
* Currently taking other psychotropic medications from which discontinuation would present a significant risk. Participants may not discontinue a satisfactory medication to participate.
* Presence or history of major depressive disorder
* Diagnosis of bipolar disorder
* A hypomanic/biphasic score of 36 or greater as rated by child's parent on the General Behavior Inventory and confirmed by clinician as indication of mood disorder
* Active substance abuse disorder or lack of control of substance use that does not allow for safe medication administration
* Evidence of current child abuse or neglect
* History of suicide attempt in the past year or current suicidal ideation with plan and/or intent
* Family history of type II diabetes in two or more first degree relatives, defined as biological parents and/or full biological siblings
6 Years
12 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Mental Health (NIMH)
NIH
Michael Aman
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Michael Aman
Retiree-Faculty
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Michael G. Aman, PhD
Role: PRINCIPAL_INVESTIGATOR
Ohio State University
Oscar G. Bukstein, MD, MPH
Role: PRINCIPAL_INVESTIGATOR
University of Pittsburgh
Kenneth D. Gadow, PhD
Role: PRINCIPAL_INVESTIGATOR
State University of New York Stony Brook
Robert L. Findling, MD
Role: PRINCIPAL_INVESTIGATOR
Case Western Reserve University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
State University of New York Stony Brook
Stony Brook, New York, United States
Case Western Reserve University
Cleveland, Ohio, United States
Ohio State University Nisonger Center
Columbus, Ohio, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Aman MG, Bukstein OG, Gadow KD, Arnold LE, Molina BS, McNamara NK, Rundberg-Rivera EV, Li X, Kipp H, Schneider J, Butter EM, Baker J, Sprafkin J, Rice RR Jr, Bangalore SS, Farmer CA, Austin AB, Buchan-Page KA, Brown NV, Hurt EA, Grondhuis SN, Findling RL. What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder? J Am Acad Child Adolesc Psychiatry. 2014 Jan;53(1):47-60.e1. doi: 10.1016/j.jaac.2013.09.022. Epub 2013 Nov 18.
Kaat A, Farmer C, Gadow K, Findling RL, Bukstein O, Arnold LE, Bangalore S, McNamara N, Aman M. Factor Validity of a Proactive and Reactive Aggression Rating Scale. J Child Fam Stud. 2015 Sep 1;24(9):2734-2744. doi: 10.1007/s10826-014-0075-5. Epub 2014 Nov 27.
Farmer CA, Brown NV, Gadow KD, Arnold LE, Kolko DG, Findling RL, Molina BS, Buchan-Page KA, Rice RR Jr, Bangalore SS, Bukstein O, Rundberg-Rivera EV, McNamara N, Aman MG. Comorbid symptomatology moderates response to risperidone, stimulant, and parent training in children with severe aggression, disruptive behavior disorder, and attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2015 Apr;25(3):213-24. doi: 10.1089/cap.2014.0109.
Rundberg-Rivera EV, Townsend LD, Schneider J, Farmer CA, Molina BB, Findling RL, Gadow KD, Bukstein OG, Arnold LE, Kolko DJ, Buchan-Page KA, McNamara NK, Michel C, Austin A, Kipp H, Rice RR, Aman MG. Participant satisfaction in a study of stimulant, parent training, and risperidone in children with severe physical aggression. J Child Adolesc Psychopharmacol. 2015 Apr;25(3):225-33. doi: 10.1089/cap.2014.0097.
Arnold LE, Gadow KD, Farmer CA, Findling RL, Bukstein O, Molina BS, Brown NV, Li X, Rundberg-Rivera EV, Bangalore S, Buchan-Page K, Hurt EA, Rice R, McNamara NK, Aman MG. Comorbid anxiety and social avoidance in treatment of severe childhood aggression: response to adding risperidone to stimulant and parent training; mediation of disruptive symptom response. J Child Adolesc Psychopharmacol. 2015 Apr;25(3):203-12. doi: 10.1089/cap.2014.0104.
Gadow KD, Arnold LE, Molina BS, Findling RL, Bukstein OG, Brown NV, McNamara NK, Rundberg-Rivera EV, Li X, Kipp HL, Schneider J, Farmer CA, Baker JL, Sprafkin J, Rice RR Jr, Bangalore SS, Butter EM, Buchan-Page KA, Hurt EA, Austin AB, Grondhuis SN, Aman MG. Risperidone added to parent training and stimulant medication: effects on attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, and peer aggression. J Am Acad Child Adolesc Psychiatry. 2014 Sep;53(9):948-959.e1. doi: 10.1016/j.jaac.2014.05.008. Epub 2014 Jun 12.
Grondhuis SN, Farmer CA, Arnold LE, Gadow KD, Findling RL, Molina BSG, Kolko DJ, Buchan-Page KA, Rice RR , Jr, Butter EM, Aman MG. Standardized Observation Analogue Procedure in the Treatment of Severe Childhood Aggression Study. J Child Adolesc Psychopharmacol. 2020 Feb;30(1):48-54. doi: 10.1089/cap.2019.0109. Epub 2019 Nov 15.
Barterian JA, Arnold LE, Brown NV, Farmer CA, Williams C, Findling RL, Kolko DJ, Bukstein OG, Molina BSG, Townsend L, Aman MG. Clinical Implications From the Treatment of Severe Childhood Aggression (TOSCA) Study: A Re-Analysis and Integration of Findings. J Am Acad Child Adolesc Psychiatry. 2017 Dec;56(12):1026-1033. doi: 10.1016/j.jaac.2017.09.426. Epub 2017 Oct 6.
Farmer CA, Epstein JN, Findling RL, Gadow KD, Arnold LE, Kipp H, Kolko DJ, Butter E, Schneider J, Bukstein OG, McNamara NK, Molina BS, Aman MG. Risperidone Added to Psychostimulant in Children with Severe Aggression and Attention-Deficit/Hyperactivity Disorder: Lack of Effect on Attention and Short-Term Memory. J Child Adolesc Psychopharmacol. 2017 Mar;27(2):117-124. doi: 10.1089/cap.2016.0040. Epub 2016 Jun 27.
Gadow KD, Brown NV, Arnold LE, Buchan-Page KA, Bukstein OG, Butter E, Farmer CA, Findling RL, Kolko DJ, Molina BS, Rice RR Jr, Schneider J, Aman MG. Severely Aggressive Children Receiving Stimulant Medication Versus Stimulant and Risperidone: 12-Month Follow-Up of the TOSCA Trial. J Am Acad Child Adolesc Psychiatry. 2016 Jun;55(6):469-78. doi: 10.1016/j.jaac.2016.03.014. Epub 2016 Apr 13.
Farmer CA, Arnold LE, Bukstein OG, Findling RL, Gadow KD, Li X, Butter EM, Aman MG. The treatment of severe child aggression (TOSCA) study: Design challenges. Child Adolesc Psychiatry Ment Health. 2011 Nov 10;5(1):36. doi: 10.1186/1753-2000-5-36.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
DSIR 84-CTS
Identifier Type: -
Identifier Source: secondary_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.