Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities

NCT05301361 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 2 other identifiers: 19706345R01HD076189-08
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 3

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

Outcome Measures

Primary Outcomes (1)

• Composite score of NIHTB-CB Flanker, Dimensional Change Card Sort, List Sorting and Speeded Matching tests.

  The composite score is calculated as the average of the non-age adjusted standard scores of each of these four tests. These standard scores have a mean of 100 and SD of 15. A minimum of 3/4 valid scores is required to calculate an average composite score.

  11 weeks

Secondary Outcomes (2)

• Conners 3 ADHD Rating Scale Inattention Scale

  11 weeks

• Conners 3 ADHD Rating Scale Hyperactivity/Impulsivity Scale

  11 weeks

Study Arms (2)

Methylphenidate

ACTIVE COMPARATOR

Drug: Methylphenidate Oral Solution

Placebo

PLACEBO COMPARATOR

Drug: Methylphenidate Oral Solution

Interventions

Methylphenidate Oral Solution 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).

Methylphenidate; Placebo

Eligibility Criteria

• Age: 6 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Davis: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (3)

UC Davis MIND Institute

Sacramento, California, 95817, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

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

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; X-Linked Intellectual Disability; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Abnormalities, Multiple; Attention Deficit and Disruptive Behavior Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: March 29, 2022
• Study Start: February 1, 2023
• Primary Completion (Estimated): September 29, 2026
• Study Completion (Estimated): September 29, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

US (3)