Methylphenidate for Intellectual Disability and ADHD

Enrolling by invitation at 2 trial locations

Overseen By Elizabeth Berry-Kravis, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Davis

Must not be taking: Stimulants

Disqualifiers: Uncontrolled epilepsy, Bipolar, Psychosis, others

Compensation: Varies

Number of Visits: 1

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well a liquid form of methylphenidate (commonly used for ADHD) can enhance thinking and attention skills in children and teens with both intellectual disability and ADHD. Participants will receive both the medication and a placebo (a non-active substance) to compare their effects on cognition. The trial involves administering the medication in liquid form, with doses adjusted to find the optimal level without side effects. Children and teens diagnosed with intellectual disability and ADHD, who have an IQ below 80, and can complete certain cognitive tests are suitable candidates for the study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that methylphenidate, a common medicine for ADHD, is usually safe for children and teenagers. In a study with 2,103 children, those taking methylphenidate experienced fewer side effects than those who did not. Another review found that methylphenidate did not significantly increase the risk of serious side effects. While some side effects might occur, they are often not severe. Additionally, long-term use of methylphenidate has been linked to lower rates of depression and suicide in people with ADHD, suggesting it might help protect mental health. Overall, evidence supports methylphenidate as a safe choice for many young people with ADHD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for intellectual disability and ADHD?

Methylphenidate Oral Solution is unique because it offers a liquid form of a well-known medication often used in tablet form for treating ADHD and related symptoms. This can be especially beneficial for individuals with intellectual disabilities who might have trouble swallowing pills. Additionally, the liquid form allows for precise dosing adjustments, which can help tailor the treatment to individual needs more effectively. Researchers are excited about the potential for this formulation to improve compliance and outcomes in patients who struggle with traditional pill forms.

What evidence suggests that methylphenidate might be an effective treatment for intellectual disability and ADHD?

Research shows that methylphenidate, which participants in this trial may receive, helps treat ADHD symptoms. Studies have found that children taking ADHD medications, such as methylphenidate, experience fewer injuries, highlighting its positive effects on behavior and attention. A review found that methylphenidate improved quality of life more than a placebo, offering moderate benefits. Another study demonstrated that methylphenidate effectively reduces main ADHD symptoms and improves overall functioning. These findings suggest that methylphenidate can benefit people with ADHD, including those with intellectual disabilities. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Methylphenidate Oral Solution

Trial Overview The 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.

How Is the Trial Designed?

Group I: Methylphenidate Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

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+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on methylphenidate controlled-delivery capsules (Equasym XL, Metadate CD) in the treatment of children and adolescents with attention-deficit hyperactivity disorder. Anderson, VR., Keating, GM.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0890856724003046

Systematic Review and Meta-Analysis: Effects of ... The analysis showed that medications such as amphetamines, methylphenidate, and atomoxetine improved QoL compared to placebo, with moderate effect sizes.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00304681

An Effectiveness and Safety Study of CONCERTA* vs. ... The purpose of this study is to see how effective and safe Concerta* is vs. immediate release methylphenidate in children with ADHD. Patients will take either ...

3. thelancet.com thelancet.com/journals/lanpsy/article/PIIS2215-0366(18)30269-4/fulltext

Comparative efficacy and tolerability of medications for ... We focused on a series of clinically relevant outcomes—namely, efficacy on ADHD core symptoms, global clinical functioning, tolerability ...

4. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2019.18111296

Continued Benefits of Methylphenidate in ADHD After 2 ... Continued treatment with methylphenidate remains effective after long-term use. Some individual patients may, however, be withdrawn from methylphenidate ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6494554/

Methylphenidate for attention deficit hyperactivity disorder ... Similarly, ADHD drugs decreased injuries among 5‐ to 10‐year‐old children from 32% to 44%, when compared to ADHD children without treatment (Dalsgaard 2015a).

6. sciencedirect.com sciencedirect.com/science/article/pii/S0149763419302350

Neurological and psychiatric adverse effects of long-term ... Several studies suggest that long-term MPH may reduce depression and suicide in ADHD. Evidence suggests caution in specific groups including pre-school children ...

7. link.springer.com link.springer.com/article/10.1007/s43440-025-00763-0

Current insights into the safety and adverse effects of ... When compared to lithium, IR MPH did not significantly impact ADHD symptoms or mental health outcomes, though results remained uncertain.

8. withpower.com withpower.com/trial/phase-1-attention-deficit-hyperactivity-disorder-adhd-10-2022-bc0b5

Methylphenidate for Intellectual Disability and ADHD In a 5-year study involving 2103 children with ADHD, those treated with methylphenidate experienced significantly fewer adverse events (AEs) compared to those ...

9. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009885.pub3/full

Methylphenidate for children and adolescents with ... Methylphenidate may not affect serious adverse events (risk ratio (RR) 0.80, 95% CI 0.39 to 1.67; I² = 0%; 26 trials, 3673 participants; very ...