Attention-deficit/Hyperactivity DisorderPhase 4NCT02039908
Examining Tolerance to CNS Stimulants in ADHD
A Phase 4 study testing Methylphenidate in people with Attention-deficit/Hyperactivity Disorder, run by Florida International University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Attention-deficit/Hyperactivity Disorder
- What is being tested?
- Methylphenidate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 267 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2013to Mar 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of attention-deficit/hyperactivity disorder
- Full Scale IQ above 80
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Florida International University Center for Children and Families
Miami, Florida, 33199
About this study
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.
Read the 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
- Being tested
- Methylphenidate
- Keywords
- Tolerance to stimulant medication
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylphenidateDrug
Also called Concerta
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.
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate 7-day dosing | Active comparator | During the school year, children in this arm will receive 7-day dosing of medication. Receives: Drug: Methylphenidate |
| Methylphenidate 5-day dosing | Active comparator | During the school year phase, these children will receive 5-day dosing with weekend holidays. Receives: Drug: Methylphenidate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10 months
Secondary outcomes (2)
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.
Measured: 10 months
Endpoint Medication Dose
Dose of medication reported in mg/kg/day
Measured: End of Phase 2 School Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2014 (estimated)
- Study startApr 2013
- Primary completionMay 2018
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Attention-deficit/Hyperactivity DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 267 participants (actual)
Sponsor and investigators
- Lead sponsor
- Florida International University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William E Pelham, Ph.D., Principal investigator, Florida International UniversityJames M Swanson, Ph.D., Principal investigator, Florida International University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02039908
- Sponsor's protocol ID
- MH099030
- Status last verified
- May 2020
- First submitted
- 7 Mar 2013
- Last updated
- 9 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 35604744
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Examining Tolerance to CNS Stimulants in ADHD
- ClinicalTrials.gov ID
- NCT02039908
- Acronym / sponsor ID
- MH099030
- Conditions
- Attention-deficit/Hyperactivity Disorder
- Keywords
- Tolerance to stimulant medication
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 267 participants (actual)
- Lead sponsor
- Florida International UniversityUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- May 2018 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 20 Jan 2014 (estimated)
- Results
- Posted 17 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate 7-day dosing | Active comparator | Drug: MethylphenidateDuring the school year, children in this arm will receive 7-day dosing of medication. |
| Methylphenidate 5-day dosing | Active comparator | Drug: MethylphenidateDuring the school year phase, these children will receive 5-day dosing with weekend holidays. |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Diagnosis of attention-deficit/hyperactivity disorder
- Full Scale IQ above 80
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylphenidateAlso: ConcertaChildren 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. | Drug | Methylphenidate 5-day dosing, Methylphenidate 7-day dosing |
Primary outcome
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.
2 secondary outcomes
Time to First Dose Increase
Time frame: 10 months
Endpoint Medication Dose
Time frame: End of Phase 2 School Year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35604744Pelham 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.
- Center for Children and Families General InformationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William E Pelham, Ph.D. principal investigator
Florida International University
James M Swanson, Ph.D. principal investigator
Florida International University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methylphenidate in people with Attention-deficit/Hyperactivity Disorder, run by Florida International University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Dose Changes Required Per Protocol (time frame: 10 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02039908, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2020.