Clinical trial NCT02039908: Examining Tolerance to CNS Stimulants in ADHD
Official title: Examining Tolerance to CNS Stimulants in ADHD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Attention-deficit/Hyperactivity Disorder
Keywords: Tolerance to stimulant medication
Lead sponsor: Florida International University
Sponsor class: OTHER
First posted: 2014-01-20
Enrollment: 267
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Dose Changes Required Per Protocol
timeFrame: 10 months
Secondary outcomes:
measure: Time to First Dose Increase
timeFrame: 10 months
measure: Endpoint Medication Dose
timeFrame: End of Phase 2 School Year
Other outcomes:
Locations:
city: Miami
country: United States
facility: Florida International University Center for Children and Families
state: Florida
Study officials:
affiliation: Florida International University
name: William E Pelham, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Florida International University
name: James M Swanson, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pelham WE, Altszuler AR, Merrill BM, Raiker JS, Macphee FL, Ramos M, Gnagy EM, Greiner AR, Coles EK, Connor CM, Lonigan CJ, Burger L, Morrow AS, Zhao X, Swanson JM, Waxmonsky JG, Pelham WE. The effect of stimulant medication on the learning of academic curricula in children with ADHD: A randomized crossover study. J Consult Clin Psychol. 2022 May;90(5):367-380. doi: 10.1037/ccp0000725.