Examining Tolerance to CNS Stimulants in ADHD

NCT ID: NCT02039908

Last Updated: 2020-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 267 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2020-03-31

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.

Conditions

Attention-deficit/Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Methylphenidate 7-day dosing

During the school year, children in this arm will receive 7-day dosing of medication.

Group Type: ACTIVE_COMPARATOR

Methylphenidate

Intervention Type: DRUG

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.

Methylphenidate 5-day dosing

During the school year phase, these children will receive 5-day dosing with weekend holidays.

Group Type: ACTIVE_COMPARATOR

Methylphenidate

Intervention Type: DRUG

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.

Interventions

Methylphenidate

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.

Intervention Type: DRUG

Other Intervention Names

Concerta

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Florida International University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William E Pelham, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Florida International University

James M Swanson, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Florida International University

Locations

Florida International University Center for Children and Families

Miami, Florida, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35604744 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://ccf.fiu.edu

Center for Children and Families General Information

Other Identifiers

MH099030

Identifier Type: -

Identifier Source: org_study_id