Intellectual DisabilityPhase 1NCT05301361
Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
A Phase 1 study testing Methylphenidate Oral Solution in people with Intellectual Disability and Fragile X Syndrome, run by University of California, Davis at 3 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 6 to 24 years
- Conditions the study is for
- Intellectual Disability, Fragile X Syndrome, Down Syndrome
- What is being tested?
- Methylphenidate Oral Solution
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Feb 2023to 29 Sep 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites
Rush University
Chicago, Illinois, 60612
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
UC Davis MIND Institute
Sacramento, California, 95817
About this study
Official title: Sensitivity of the NIH Toolbox Cognition Battery to Stimulant Treatment in Intellectual Disabilities
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
- Being tested
- Methylphenidate Oral Solution
- Medical subject headings
- Intellectual Disability, Fragile X Syndrome, Down Syndrome, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylphenidate Oral SolutionDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate | Active comparator | Not described Receives: Drug: Methylphenidate Oral Solution |
| Placebo | Placebo comparator | Not described Receives: Drug: Methylphenidate Oral Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 11 weeks
Secondary outcomes (2)
Conners 3 ADHD Rating Scale Inattention Scale
Measured: 11 weeks
Conners 3 ADHD Rating Scale Hyperactivity/Impulsivity Scale
Measured: 11 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2022
- Study start1 Feb 2023
- Primary completion29 Sep 2026 (estimated)
- Study completion29 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intellectual DisabilityStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05301361
- Sponsor's protocol ID
- 1970634
- Other IDs
- 5R01HD076189-08
- Status last verified
- Dec 2025
- First submitted
- 8 Mar 2022
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sensitivity of the NIH Toolbox Cognition Battery to Stimulant Treatment in Intellectual Disabilities
- ClinicalTrials.gov ID
- NCT05301361
- Acronym / sponsor ID
- 1970634
- Conditions
- Intellectual Disability, Fragile X Syndrome, Down Syndrome, Attention Deficit Hyperactivity Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 1 Feb 2023 (actual)
- Primary completion
- 29 Sep 2026 (estimated)
- Study completion
- 29 Sep 2026 (estimated)
- First posted
- 29 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate | Active comparator | Drug: Methylphenidate Oral Solution |
| Placebo | Placebo comparator | Drug: Methylphenidate Oral Solution |
Who may qualify
- Ages
- 6 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylphenidate Oral SolutionThe 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). | Drug | Methylphenidate, Placebo |
Primary outcome
Composite score of NIHTB-CB Flanker, Dimensional Change Card Sort, List Sorting and Speeded Matching tests.
Time frame: 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.
2 secondary outcomes
Conners 3 ADHD Rating Scale Inattention Scale
Time frame: 11 weeks
Conners 3 ADHD Rating Scale Hyperactivity/Impulsivity Scale
Time frame: 11 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
Related trials for Intellectual Disability
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
Not yet recruiting
Advancing Cardiovascular Health Among Adolescents With Intellectual Disabilities: Co-Development of Technology Interventions to Enhance Physical Activity
Physical Activity, Intellectual Disabilities
RecruitingObservational study
Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
Congenital Disorders of Glycosylation
RecruitingObservational study
Genome Medical Sequencing for Gene Discovery
Intellectual Disabilities, Congenital Anomaly
RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Methylphenidate Oral Solution in people with Intellectual Disability and Fragile X Syndrome, run by University of California, Davis at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite score of NIHTB-CB Flanker, Dimensional Change Card Sort, List Sorting and Speeded Matching tests. (time frame: 11 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.