Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities

Sponsor
University of California, Davis (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05301361
Collaborator
(none)
68
2
46.9

Study Details

Study Description

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 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Methylphenidate Oral Solution
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
68 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
Sensitivity of the NIH Toolbox Cognition Battery to Stimulant Treatment in Intellectual Disabilities
Anticipated Study Start Date :
Nov 1, 2022
Anticipated Primary Completion Date :
Sep 29, 2025
Anticipated Study Completion Date :
Sep 29, 2026

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Methylphenidate

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).

Placebo Comparator: Placebo

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).

Outcome Measures

Primary Outcome Measures

  1. Composite score of NIHTB-CB Flanker, Dimensional Change Card Sort, List Sorting and Speeded Matching tests. [11 weeks]

    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.

Secondary Outcome Measures

  1. Conners 3 ADHD Rating Scale Inattention Scale [11 weeks]

  2. Conners 3 ADHD Rating Scale Hyperactivity/Impulsivity Scale [11 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Years to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • University of California, Davis

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
David Hessl, PhD, Professor of Clinical Psychiatry, University of California, Davis
ClinicalTrials.gov Identifier:
NCT05301361
Other Study ID Numbers:
  • ToolboxStim
First Posted:
Mar 29, 2022
Last Update Posted:
Mar 29, 2022
Last Verified:
Mar 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 29, 2022