68 Participants Needed

Methylphenidate for Intellectual Disability and ADHD

Recruiting at 2 trial locations
AD
JJ
EG
CE
EB
Overseen ByElizabeth Berry-Kravis, MD
Age: < 65
Sex: Any
Trial Phase: Phase 1
Sponsor: University of California, Davis

Trial Summary

What is the purpose of this trial?

This study is a randomized, double-blind, placebo-controlled, crossover trial of extended-release liquid methylphenidate (XRMPH) to evaluate the sensitivity of the NIH Toolbox Cognition Battery (NIHTB-CB) to changes in cognition in children and adolescents ages 6 to 17 with intellectual disability (D) and comorbid Attention Deficit Hyperactivity Disorder (ADHD). The sample will include 68 males or females (expected male: female ratio of 1.8:1 with ID and ADHD as determined by structured diagnostic interview and Conners 3 scores. Additional inclusion criteria will include Full Scale IQ above 50 and mental age greater than or equal to 3 years. In addition, participants must be able to complete NIHTB-CB testing and provide valid scores at baseline. After baseline testing, participants will then be randomized to drug or placebo in a 1:1 ratio (N=34 per group) at the end of the baseline visit. XRMPH in oral suspension supplied as Quillivant XR in 5 mg/ml (Tris Pharma, Monmouth Junction, NJ) will be the active treatment. The XRMPH or matching placebo will be started at a dose of 0.3 mg/kg/day and individually titrated over two weeks. Phone calls at the end of weeks 1, 2, and 3 will be used to collect adverse event and response data. If there is no evidence of side effects and ongoing symptoms of ADHD, the dose will be increased to 0.5 mg/kg/day at one week and 0.7 mg/kg/day at 2 weeks (maximum dose of 60 mg per day consistent with FDA labeled use in youth). The Clinical Global Impression (CGI) will be used as a guide to define optimal dose. If side effects occur the dose will be reduced to the dose level at which there were no side effects. Final optimal dose will be established by the end of week 3 and this will be maintained for 2 weeks until 5 weeks post randomization, at which time the follow-up parent and teacher Conners scales, NIHTB-CB, Go/No-Go, and PedsQL will be completed. Participants will have a washout period of 1 week, will then complete re-assessment at the second baseline, and then will cross over to the other treatment (Quillivant to placebo; placebo to Quillivant), also in a double-blind fashion. In the second treatment arm, patients will have the same titration, monitoring and treatment periods as in the first arm, again followed by repeated assessments at the conclusion of 5 weeks. The accrual of participants and number of visits is shown in the Timeline per 6-month period.

Will I have to stop taking my current medications?

The trial requires that you stop taking any stimulant medications at least 2 weeks before joining. If you're on other types of medications, the protocol doesn't specify, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Methylphenidate Oral Solution for treating Intellectual Disability and ADHD?

Research shows that methylphenidate is effective in reducing ADHD symptoms in children, adolescents, and adults. It has been studied in various forms, including controlled-delivery and osmotic-release systems, and has shown positive results in managing ADHD symptoms, which may suggest potential benefits for those with intellectual disabilities as well.12345

Is methylphenidate safe for humans?

Research shows that methylphenidate, used for treating ADHD in children and adolescents, has been studied for safety over several years. While it can cause some side effects, it is generally considered safe when used as prescribed.678910

How does the drug Methylphenidate Oral Solution differ from other treatments for ADHD and intellectual disability?

Methylphenidate Oral Solution is unique because it is an oral liquid form, which can be easier to administer for individuals who have difficulty swallowing pills. This form of methylphenidate is designed to help manage symptoms of ADHD by increasing levels of certain chemicals in the brain, similar to other forms of methylphenidate, but its liquid form offers a different administration option.311121314

Eligibility Criteria

This trial is for children and adolescents aged 6-17 with intellectual disabilities (ID) like Down Syndrome or Fragile X, who also have ADHD. They must have an IQ above 50 but below 80, a mental age of at least 4 years, and be able to complete certain cognitive tests. Those recently on stimulants or with conditions like uncontrolled epilepsy or severe psychiatric disorders cannot participate.

Inclusion Criteria

My mental age is 4 years or older according to the Stanford Binet test.
You have been diagnosed with intellectual disability.
I can complete the required cognitive tests.
See 2 more

Exclusion Criteria

You have had a bad reaction to stimulant medications in the past.
You have taken stimulant medications in the two weeks before the study starts.
Someone who lives with you has a current problem with drugs or alcohol.
See 1 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Baseline testing and randomization to drug or placebo

1 week

Treatment

Participants receive XRMPH or placebo with dose titration over 3 weeks, followed by 2 weeks at optimal dose

5 weeks
Phone calls at the end of weeks 1, 2, and 3

Washout

Participants undergo a washout period before crossover

1 week

Crossover Treatment

Participants switch to the alternate treatment with the same titration and monitoring as the first arm

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Methylphenidate Oral Solution
Trial OverviewThe study tests if extended-release liquid methylphenidate (a medication commonly used for ADHD) affects cognition in participants with ID and ADHD. It's a double-blind trial where half the kids get the drug and half get a placebo without knowing which one they're taking. The dose starts low and can increase unless side effects appear.
Participant Groups
2Treatment groups
Active Control
Placebo Group
Group I: MethylphenidateActive Control1 Intervention
Group II: PlaceboPlacebo Group1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials
958
Recruited
4,816,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials
2,103
Recruited
2,760,000+

Findings from Research

Controlled-delivery methylphenidate (methylphenidate CD) is effective and well tolerated for treating ADHD in children aged 6 and older, showing superior control of symptoms compared to osmotic release methylphenidate during a typical school day.
In clinical trials lasting 3 weeks, methylphenidate CD was found to be more effective than a placebo and equally effective as immediate-release methylphenidate, making it a strong option for managing ADHD symptoms during school hours.
Methylphenidate controlled-delivery capsules (EquasymXL, Metadate CD): a review of its use in the treatment of children and adolescents with attention-deficit hyperactivity disorder.Anderson, VR., Keating, GM.[2018]
In a 5-year study involving 2103 children with ADHD, those treated with methylphenidate experienced significantly fewer adverse events (AEs) compared to those treated with atomoxetine, indicating a better safety profile for methylphenidate.
Overall, 26.8% of participants reported mild AEs and 3.9% reported severe AEs, with atomoxetine associated with higher rates of both mild and severe AEs, including gastrointestinal and neuropsychiatric issues.
Safety of Methylphenidate and Atomoxetine in Children with Attention-Deficit/Hyperactivity Disorder (ADHD): Data from the Italian National ADHD Registry.Cortese, S., Panei, P., Arcieri, R., et al.[2018]
In a 12-week study involving 55 adolescents treated with osmotic-release oral system methylphenidate (MPH) for ADHD, both patients and parents reported similar adverse events (AEs), but clinicians identified more AEs, especially at week 6, suggesting the need for comprehensive reporting methods.
The study highlights the importance of using a drug-specific checklist for clinicians to better capture AEs, as differences in reported AEs between patients and parents indicate that gathering information from both sources can provide a fuller picture of the treatment's safety.
Two different solicitation methods for obtaining information on adverse events associated with methylphenidate in adolescents: a 12-week multicenter, open-label study.Lee, MS., Lee, SI., Hong, SD., et al.[2015]

References

Methylphenidate in children with ADHD with or without learning disability. [2019]
Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders. [2021]
Methylphenidate controlled-delivery capsules (EquasymXL, Metadate CD): a review of its use in the treatment of children and adolescents with attention-deficit hyperactivity disorder. [2018]
Randomized, 6-Week, Placebo-Controlled Study of Treatment for Adult Attention-Deficit/Hyperactivity Disorder: Individualized Dosing of Osmotic-Release Oral System (OROS) Methylphenidate With a Goal of Symptom Remission. [2018]
The acute effect of methylphenidate in Brazilian male children and adolescents with ADHD: a randomized clinical trial. [2017]
Safety of Methylphenidate and Atomoxetine in Children with Attention-Deficit/Hyperactivity Disorder (ADHD): Data from the Italian National ADHD Registry. [2018]
Two different solicitation methods for obtaining information on adverse events associated with methylphenidate in adolescents: a 12-week multicenter, open-label study. [2015]
Methylphenidate and dexmethylphenidate formulations for children with attention-deficit/hyperactivity disorder. [2019]
Long-acting versus short-acting methylphenidate for paediatric ADHD: a systematic review and meta-analysis of comparative efficacy. [2022]
Update on methylphenidate and dexmethylphenidate formulations for children with attention-deficit/hyperactivity disorder. [2021]
Spotlight on methylphenidate controlled-delivery capsules (Equasym XL, Metadate CD) in the treatment of children and adolescents with attention-deficit hyperactivity disorder. [2019]
12.United Statespubmed.ncbi.nlm.nih.gov
Methylphenidate: established and expanding roles in symptom management. [2022]
13.United Statespubmed.ncbi.nlm.nih.gov
Comparative Efficacy of Methylphenidate and Atomoxetine on Social Adjustment in Youths with Attention-Deficit/Hyperactivity Disorder. [2021]
[Sustained effectiveness of osmotic-release methylphenidate: a study of 266 cases]. [2015]