Examining Tolerance to CNS Stimulants in ADHD

• ClinicalTrials.gov Identifier: NCT02039908
• Recruitment Status: Completed
• First Posted: January 20, 2014
• Results First Posted: September 17, 2019
• Last Update Posted: June 9, 2020
• Sponsor: Florida International University
• Information provided by (Responsible Party): Florida International University

Tracking Information

• First Submitted Date: March 7, 2013
• First Posted Date: January 20, 2014
• Results First Submitted Date: July 29, 2019
• Results First Posted Date: September 17, 2019
• Last Update Posted Date: June 9, 2020
• Study Start Date: April 2013
• Actual Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2019)

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.

Original Primary Outcome Measures (submitted: January 16, 2014)

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.

Current Secondary Outcome Measures (submitted: August 27, 2019)

• 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.
• Endpoint Medication Dose [ Time Frame: End of Phase 2 School Year ]
  Dose of medication reported in mg/kg/day

Original Secondary Outcome Measures (submitted: January 16, 2014)

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 weeks.

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: January 16, 2014)

Symptom ratings [ Time Frame: 12 months ]

ADHD symptoms will be measured at the end of the school year along with associated measures of social skills and academic performance.

Descriptive Information

• Brief Title: Examining Tolerance to CNS Stimulants in ADHD
• Official Title: Examining Tolerance to CNS Stimulants in ADHD

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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Attention-deficit/Hyperactivity Disorder

Intervention

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 Name: Concerta

Study Arms

• Active Comparator: Methylphenidate 7-day dosing
  During the school year, children in this arm will receive 7-day dosing of medication.
  Intervention: Drug: Methylphenidate
• Active Comparator: Methylphenidate 5-day dosing
  During the school year phase, these children will receive 5-day dosing with weekend holidays.
  Intervention: Drug: Methylphenidate

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 27, 2019): 267
• Original Estimated Enrollment (submitted: January 16, 2014): 250
• Actual Study Completion Date: March 2020
• Actual Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 12 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02039908
• Other Study ID Numbers: MH099030
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Florida International University
• Original Responsible Party: Same as current
• Current Study Sponsor: Florida International University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Florida International University
• Verification Date: May 2020