Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities

Attention Deficit Hyperactivity Disorder Clinical Trial

Official title:

Sensitivity of the NIH Toolbox Cognition Battery to Stimulant Treatment in Intellectual Disabilities

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05301361
• Other study ID #: 1970634
• Secondary ID: 5R01HD076189-08
• Status: Enrolling by invitation
• Phase: Phase 1
• Start date: February 1, 2023
• Est. completion date: September 29, 2026

Study information

• Verified date: August 2023
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 4 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 68
• Est. completion date: September 29, 2026
• Est. primary completion date: September 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

• IQ above 50 and below 80
• Mental age 4.0 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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).

Locations

Country	Name	City	State
United States	Rush University	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	UC Davis MIND Institute	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Davis	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Conners 3 ADHD Rating Scale Inattention Scale		11 weeks
Secondary	Conners 3 ADHD Rating Scale Hyperactivity/Impulsivity Scale		11 weeks