Treatment of Children With ADHD Who do Not Fully Respond to Stimulants (TREAT)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Developing More Efficacious Treatments for Children With ADHD Who Are "Partial" or "Non-responders" to Stimulants|
- ADHD Rating Scale - IV (ADHD-RS-IV) [ Time Frame: weekly ] [ Designated as safety issue: No ]
- Clinical Global Impressions - Improvement (CGI-I) [ Time Frame: weekly ] [ Designated as safety issue: No ]
- Children's Global Assessment Scale (C-GAS) [ Time Frame: pre and post treatment ] [ Designated as safety issue: No ]
- Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: weekly ] [ Designated as safety issue: Yes ]
- Barnes-Akathisia Rating Scale (BARS) [ Time Frame: weekly ] [ Designated as safety issue: Yes ]
- Simpson-Angus Scale (SAS) [ Time Frame: weekly ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2006|
|Study Completion Date:||February 2009|
|Primary Completion Date:||February 2008 (Final data collection date for primary outcome measure)|
Active Comparator: aripiprazole
This treatment arm (also called the "combination arm") consists of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus augmentation with aripiprazole. Aripriprazole pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Dosing will start at 2.5 mg and will be titrated up to 5 mg by week 1, and up to 10 mg by week 2 and for the remainder of the trial.
double blind capsules (abilify or placebo) taken once daily, up to 10mg.
Other Name: Abilify
Placebo Comparator: Sugar pill
This treatment arm (also called the "simple treatment" arm) will consist of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus a placebo matching aripiprazole. Placebo pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis.
We propose to do this with a single site, ten week, pilot study of 40 school age children, ages 6-17, with Attention-Deficit/ Hyperactivity Disorder (ADHD) and moderate or greater impairment (C-GAS < 55) who show ADHD symptoms despite a trial in the community with their primary care practitioner with either of two of the most commonly used stimulants (i.e., either OROS-MPH (Concerta) or mixed salts of amphetamine (Adderall-XR)).
These children first will be classified into three groups: Group 1, those who had been treated with a maximal dose of stimulant with partial or no response; Group 2, those treated with a suboptimal dose of stimulant and showing partial or no response, and Group 3, those who developed side effects that limited continued treatment with optimal doses of a stimulant.
The next step will be to enter these children into an open, two week trial to confirm their treatment resistance. Group 2, those treated with suboptimal doses, will have the dosage increased to the maximum recommended stimulant dose. Group 1, those who had been treated for 4 weeks with maximal doses of a stimulant, or Group 3, those who developed moderate to severe drug-related side effects, will be switched to the other class of stimulant for a two week trial, unless they have been tried on both classes. Those children will be maintained on their current class of stimulant for two weeks. At the end of the two weeks, all children will be rated on the ADHD-IV-RS by the Study Doctor. Those who have shown moderate to severe side effects or those who respond will exit the trial and be treated openly. Children from Group 2 who continue to show no improvement after a week will switch to the other stimulant. All children from Group 2 tried on both stimulants and all children from Groups 1 and 3 who continue to show mean scores greater than 1 SD over the mean for age will be referred to Phase 2.
During phase 2, they will be randomized to one of two treatment arms for eight weeks. The first treatment arm, the "simple treatment" arm, will consist of parent training plus continued treatment with a stimulant that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response, plus a placebo matching aripiprazole. The second treatment arm, called the "combination" arm, will consist of parent training plus continued treatment on stimulant plus augmentation with a second generation antipsychotic (aripiprazole). Aripiprazole (Abilify™ ) is a product that is FDA-approved and marketed for the treatment of schizophrenia and for the treatment of acute manic episodes associated with Bipolar I Disorder in adults only. However, aripiprazole is also used to treat children and adolescents with aggressive and oppositional disorders in standard clinical practice. We will continue randomizing patients until we have 40 children with ADHD become eligible to enter Phase 2.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00279409
|United States, New York|
|New York State Psychiatric Institute|
|New York, New York, United States, 10032|
|Principal Investigator:||Laurence L Greenhill, MD||New York State Psychiatric Institute|