Clinical trial NCT05301361: Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
Official title: Sensitivity of the NIH Toolbox Cognition Battery to Stimulant Treatment in Intellectual Disabilities
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Intellectual Disability
Fragile X Syndrome
Down Syndrome
Attention Deficit Hyperactivity Disorder
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-03-29
Enrollment: 68
Sex: ALL
Minimum age (years): 6
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


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

Primary outcomes:
measure: Composite score of NIHTB-CB Flanker, Dimensional Change Card Sort, List Sorting and Speeded Matching tests.
timeFrame: 11 weeks
Secondary outcomes:
measure: Conners 3 ADHD Rating Scale Inattention Scale
timeFrame: 11 weeks
measure: Conners 3 ADHD Rating Scale Hyperactivity/Impulsivity Scale
timeFrame: 11 weeks
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis MIND Institute
state: California
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
Study officials:
References: