Examining Tolerance to CNS Stimulants in ADHD

May 29, 2020 updated by: Florida International University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

267

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33199
        • Florida International University Center for Children and Families

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Methylphenidate 7-day dosing
During the school year, children in this arm will receive 7-day dosing of medication.
Drug: 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.
Other Names:
  • Concerta
Active Comparator: Methylphenidate 5-day dosing
During the school year phase, these children will receive 5-day dosing with weekend holidays.
Drug: 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.
Other Names:
  • Concerta

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Dose Changes Required Per Protocol
Time Frame: 10 months
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
Time Frame: 10 months
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
Time Frame: End of Phase 2 School Year
Dose of medication reported in mg/kg/day
End of Phase 2 School Year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Florida International University

Investigators

  • Principal Investigator: William E Pelham, Ph.D., Florida International University
  • Principal Investigator: James M Swanson, Ph.D., Florida International University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

May 1, 2018

Study Completion (Actual)

March 1, 2020

Study Registration Dates

First Submitted

March 7, 2013

First Submitted That Met QC Criteria

January 16, 2014

First Posted (Estimate)

January 20, 2014

Study Record Updates

Last Update Posted (Actual)

June 9, 2020

Last Update Submitted That Met QC Criteria

May 29, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MH099030

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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