Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities

NCT ID: NCT05301361

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2026-09-29

Brief Summary

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.

Conditions

Intellectual Disability; Fragile X Syndrome; Down Syndrome; Attention Deficit Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Methylphenidate

Group Type: ACTIVE_COMPARATOR

Methylphenidate Oral Solution

Intervention Type: DRUG

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).

Placebo

Group Type: PLACEBO_COMPARATOR

Methylphenidate Oral Solution

Intervention Type: DRUG

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).

Interventions

Methylphenidate Oral Solution

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).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• IQ below 80
• Mental age 3.0 or higher (Stanford Binet)
• Diagnosis of Intellectual Disability
• Diagnosis of ADHD
• Ability to complete valid NIHTB-CB tests at screening/baseline

Exclusion Criteria

• stimulant use within 2 weeks prior to randomization
• history of a sensitivity reaction to stimulants
• presence of significant comorbid psychiatric or medical disorder/illness deemed by the site physician as inappropriate for stimulant use (uncontrolled epilepsy, bipolar disorder, psychosis, severe OCD, hypertension, tachycardia hypertension, failure to thrive, psychosis for example)
• a household resident with a current substance abuse disorder

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 24 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UC Davis MIND Institute

Sacramento, California, United States

Rush University

Chicago, Illinois, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Countries

United States

Other Identifiers

5R01HD076189-08

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1970634

Identifier Type: -

Identifier Source: org_study_id