Examining Tolerance to CNS Stimulants in ADHD

Study Overview
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Brief Summary
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Although stimulant medication is a well-established treatment for ADHD, it is often necessary for doctors to increase the dose over time to maintain the benefits of the medication. While medication can be very effective for improving symptoms of ADHD during the first year of use, it has not been found to significantly improve the long term course of children with ADHD. For example, in large research studies, groups of children who take medication for ten years do not have consistently better academic grades than groups of children who never used medication (individual results will vary from child to child). In order to help children with ADHD achieve the best possible outcomes, it is important for doctors to study why this happens. One possible reason is development of tolerance to the medication. Tolerance means that a drug's effects decrease when it is taken consistently over time, so that an increased dose is needed to continue showing effects. Some doctors believe that children who take stimulant medication for ADHD develop tolerance to it which would explain why benefits may not persist over time, but no research studies have been done to measure whether this occurs. This study aims to see if children show a tolerance effect to stimulant medication and whether that tolerance can be prevented by taking short breaks from the medication called medication holidays.

Detailed Description
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This is an innovative evaluation of tolerance using an objective measure in an analog classroom. Each subject will complete the a 10-minute math test twice a day for three weeks on optimal dose or placebo, and then be crossed over to the other condition. Within-subject drug/placebo differences will be compared over the three weeks of exposure to assess tolerance in the analog setting. When school commences, 50% of the sample will be randomized to 7-day-a-week (continuous) dosing and 50% to 5-day-a- week (weekend holidays) dosing to examine the efficacy of prescribed weekend drug holidays for combatting need for dose escalations (tolerance) during the school year. Participants will be assessed monthly to detect deteriorating functioning. Using a standardized protocol, study physicians will increase dose for subjects in either arm who meet defined impairment thresholds. The difference between the two dosing conditions will inform regarding how best to deal with tolerance in clinical application.

Official Title
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Examining Tolerance to CNS Stimulants in ADHD

Conditions
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Attention-deficit/Hyperactivity Disorder

Intervention / Treatment
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* Drug: Methylphenidate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of attention-deficit/hyperactivity disorder Full Scale IQ above 80 Exclusion Criteria: Psychotropic medications for conditions other than ADHD Active medical or psychiatric conditions that could be worsened by stimulants Diagnosis of Autism or Asperger's Disorder Documented intolerance fo methylphenidate or failed trial of OROS MPH

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methylphenidate 7-day dosing<br>During the school year, children in this arm will receive 7-day dosing of medication. | Drug: Methylphenidate<br>* Children will receive a double-blind assessment to determine their optimal starting dose of Concerta. Doses will be adjusted over the course of the school year and inceased if tolerance to the medication is detected.<br>* Other names: Concerta;|
| Active Comparator: Methylphenidate 5-day dosing<br>During the school year phase, these children will receive 5-day dosing with weekend holidays. | Drug: Methylphenidate<br>* Children will receive a double-blind assessment to determine their optimal starting dose of Concerta. Doses will be adjusted over the course of the school year and inceased if tolerance to the medication is detected.<br>* Other names: Concerta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Dose Changes Required Per Protocol | Monthly evaluations of medication efficacy will be used to determine whether dose adjustments are needed due to anticipated tolerance effects. | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Dose Increase | The amount of time elapsed before a child requires a dose increase during the school year will be measured in months. | 10 months | 
| Endpoint Medication Dose | Dose of medication reported in mg/kg/day | End of Phase 2 School Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tolerance to stimulant medication