Sickle Cell DiseasePhase 1NCT07226219
Methylphenidate to Address Attention and Executive Deficits Among Children With Sickle Cell Disease
A Phase 1 study testing Extended-Release Methylphenidate in people with Sickle Cell Disease and Executive Dysfunction, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
The purpose of this study is to determine if patients with sickle cell disease (SCD) can consistently take a drug called Methylphenidate (MPH) daily, once a day for 4 weeks to help with any thinking, attention or schoolwork problems and if they have any side effects. Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Sickle Cell Disease, Executive Dysfunction, Cognitive Impairment
- What is being tested?
- Extended-Release Methylphenidate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Nov 2025to 1 Aug 2028
- Phase
- Phase 1
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 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosed with SCD
- Enrolled on the institutional protocol: Sickle Cell Clinical Research Intervention Program (SCCRIP)
- Between the ages of 8.0 and 17.9 years
- Included if performance measure, rating scale or diagnostic criteria met (within the past 2 years):
- *Score at or below a Standard Score of 85 (16th percentile) on any 2 out of 4 performance measures:
- NIH Toolbox Flanker
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- NIH Toolbox List Sorting
- NIH Toolbox Dimensional Change Card Sort Test (DCST)
- Wechsler Intelligence Scale for Children (WISC) -5/ Wechsler Adult Intelligence Scale (WAIS)-4 Digit Span Forward (DSF)
- *Score at or above a T Score of 60 (84th percentile) on any 1 out of 2 parent rating scales:
- BRIEF-2 Global Executive
- BASC-3 Attention
- *Have a documented diagnosis of attention deficit / hyperactivity disorder (any subtype)
- English as the primary language
- Research participant and one caregiver willing to participate and provide consent/assent according to institutional guidelines
- Negative pregnancy test in female participant of childbearing age
Who cannot join
- Primary language other than English
- Score below the 2nd percentile on the Wechsler Abbreviated Scale of Intelligence (WASI)-2 intelligence quotient (IQ) test (ever)
- Uncontrolled seizures (seizure within the past 6 months)
- Cardiomyopathy or known congenital structural cardiac defects
- Stenotic valvular disease, left coronary artery stenosis, or history of myocarditis or pericarditis
- History of heart arrhythmia including ventricular tachycardia, ventricular fibrillation, supraventricular tachycardia, QT prolongation or concomitant use of medications associated with QT prolongation
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- Two or more prior episodes of priapism
- Blood pressure >95th percentile at the three most recent visits consecutively (i.e., >95th percentile reading at all three of the most recent hospital visits to St. Jude).
- If blood pressure is > 95th %ile compared to age-norms on the day of the baseline visit, a repeat blood-pressure reading will be performed both electronically and manually to confirm findings.
- Stimulant medication within the past two weeks
- Severe sensory loss
- Previous adverse reaction to methylphenidate
- Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
- Currently prescribed another investigational medication.
- Diagnosed with sickle cell-hereditary persistence of fetal hemoglobin (HbSHPFH), sickle cell homozygous C (CC), Hb S/N-Baltimore, or other rare genotypes that would preclude the participant from having the classic symptoms of sickle cell disease
- Currently prescribed any of the following:
- Phenobarbital (anticonvulsant)
- Phenytoin (anticonvulsant)
- Primidone (anticonvulsant)
- Warfarin (anticoagulant)
- Antipsychotic medications
- Selective Serotonin Reuptake Inhibitor (SSRI) medications
- Tricyclic antidepressant (TCA) medications
- Vasopressor medications
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Andrew Heitzer, PhD, 888-226-4343, referralinfo@stjude.org
Andrew K Heitzer, PhD
About this study
Official title: Pilot Trial of Stimulant Treatment to Address Attention and Executive Deficits Among Children With Sickle Cell Disease
The purpose of this study is to determine if patients with sickle cell disease (SCD) can consistently take a drug called Methylphenidate (MPH) daily, once a day for 4 weeks to help with any thinking, attention or schoolwork problems and if they have any side effects.
The study will assess any thinking or attention problems participants may have both before taking this drug and after. Additionally, the study will assess the decision-making process of the caregiver that may influence using this drug or not.
Read more
Primary Objective:
- Assess the feasibility, acceptability, and adherence to MPH treatment in children with SCD and EF deficits.
Secondary Objective:
- Evaluate neurobehavioral and safety outcomes following MPH treatment.
Exploratory Objective:
- Evaluate decision-making and determinants influencing methylphenidate utilization among caregivers.
Read the detailed description
Children with sickle cell disease (SCD) are at higher risk for executive functioning (EF) deficits, including attention, working memory, and inhibitory control. These deficits are associated with poor academic performance, reduced quality of life, and challenges transitioning to adult healthcare. Despite the effectiveness of stimulant medications like methylphenidate (MPH) in improving EF in the general population and other medical groups, their use in children with SCD is rare.
This is a single-arm, open-label pilot trial conducted at St. Jude Children's Research Hospital. Thirty children with SCD and EF deficits will receive a 4-week course of extended-release MPH (10 mg or 20 mg daily, based on weight). Extended-release methylphenidate will be administered once daily for 4 weeks. The initial dose will be given in clinic, followed by home administration. Adherence will be monitored via weekly video pill counts.
The study will enroll 30 patients aged 8.0 to 17.9 years with SCD and EF impairment, along with 30 caregivers. An additional 12 caregivers who decline participation will be interviewed to assess decision-making and treatment barriers.
Neurobehavioral assessments and side effect evaluations will be conducted at baseline, immediately post-dose, and weekly during the home medication phase. Caregivers will complete rating scales and interviews to assess treatment acceptability and decision-making.
- Conditions
- Sickle Cell Disease, Executive Dysfunction, Cognitive Impairment, Attention Deficit/Hyperactivity Disorder (ADHD)
- Being tested
- Extended-Release Methylphenidate
- Keywords
- SCD, ADHD
- Medical subject headings
- Anemia, Sickle Cell, Cognitive Dysfunction, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extended-Release MethylphenidateDrug
Also called MPH
Participants will receive a weight-based dose of extended-release methylphenidate (0.6 mg/kg/day), rounded to either 10 mg or 20 mg, taken orally once daily for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate Treatment Group | Experimental | All participants in this single-arm pilot study will receive extended-release methylphenidate for 4 weeks. The intervention is designed to evaluate feasibility, acceptability, adherence, and safety of stimulant treatment in children and adolescents with sickle cell disease (SCD) and executive functioning deficits. Receives: Drug: Extended-Release Methylphenidate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess feasibility of methylphenidate
Feasibility is measured by the participation rate (i.e., ratio of those who agree to participate to those approached).
Measured: Feasibility is measured during the initial recruitment process for each participant.
Assess acceptability of methylphenidate
Acceptability is captured by parent- and self-report ratings on the Acceptability of Intervention Measure (AIM).
Measured: Acceptability ratings are captured at baseline and after 4 weeks of treatment with methylphenidate.
Assess adherence to methylphenidate
Adherence is measured through weekly pill counts. The primary adherence outcome is the ratio of the number of pills taken to those dispersed.
Measured: Adherence is measured on a weekly basis through 4 weeks of treatment
Secondary outcomes (9)
Behavior Assessment System for Children, 3rd Edition (BASC-3), Parent Report
Attention, Hyperactivity, and Depression scales are calculated. The investigators will determine the amount and pattern of missing data. The relative change (defined as (post - pre)/pre)) will be calculated for each outcome and rank these changes to determine sensitivity of the measures. The goal of measuring neurobehavioral outcomes in this pilot trial is to determine how feasible the measures are for the target population and their relative sensitivity to the effects of methylphenidate treatment.
Measured: Baseline and 4-6 weeks after treatment
Behavior Rating Inventory of Executive Function, 2nd Edition (BRIEF-2), Parent Report
Global Executive Composite Scale is calculated. The investigator will determine the amount and pattern of missing data for neurobehavioral outcomes. The relative change (defined as (post - pre)/pre)) will be calculated for each outcome and rank these changes to determine sensitivity of the measures. The goal of measuring neurobehavioral outcomes in this pilot trial is to determine how feasible the measures are for the target population and their relative sensitivity to the effects of methylphenidate treatment.
Measured: Baseline and 4-6 weeks after treatment
Pediatric Quality of Life Inventory (PedsQL) Sickle Cell Disease modules, Parent Report
The investigator will determine the amount and pattern of missing data for neurobehavioral outcomes. The relative change (defined as (post - pre)/pre)) will be calculated for each outcome and rank these changes to determine sensitivity of the measures. The goal of measuring neurobehavioral outcomes in this pilot trial is to determine how feasible the measures are for the target population and their relative sensitivity to the effects of methylphenidate treatment.
Measured: Baseline and 4-6 weeks after treatment
Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue modules, Parent Report
The investigator will determine the amount and pattern of missing data for neurobehavioral outcomes. The relative change (defined as (post - pre)/pre)) will be calculated for each outcome and rank these changes to determine sensitivity of the measures. The goal of measuring neurobehavioral outcomes in this pilot trial is to determine how feasible the measures are for the target population and their relative sensitivity to the effects of methylphenidate treatment.
Measured: Baseline and 4-6 weeks after treatment
Conners 4th Edition Short Form, Self Report
The investigator will determine the amount and pattern of missing data for neurobehavioral outcomes. The relative change (defined as (post - pre)/pre)) will be calculated for each outcome and rank these changes to determine sensitivity of the measures. The goal of measuring neurobehavioral outcomes in this pilot trial is to determine how feasible the measures are for the target population and their relative sensitivity to the effects of methylphenidate treatment.
Measured: Baseline and 4-6 weeks after treatment
NIH Toolbox Cognition
Dimensional Change Card Cort, Flanker, Pattern Comparison, Picture Sequence Memory Test, Picture Vocabulary subtests are completed. The investigator will determine the amount and pattern of missing data for neurobehavioral outcomes. The relative change (defined as (post - pre)/pre)) will be calculated for each outcome and rank these changes to determine sensitivity of the measures. The goal of measuring neurobehavioral outcomes in this pilot trial is to determine how feasible the measures are for the target population and their relative sensitivity to the effects of methylphenidate treatment.
Measured: Baseline and ~90 minutes after first dose administered
Woodcock Johnson Tests of Academic Achievement, 4th Edition (WJ-IV)
Math Fluency subtest is completed. The investigator will determine the amount and pattern of missing data for neurobehavioral outcomes. The relative change (defined as (post - pre)/pre)) will be calculated for each outcome and rank these changes to determine sensitivity of the measures. The goal of measuring neurobehavioral outcomes in this pilot trial is to determine how feasible the measures are for the target population and their relative sensitivity to the effects of methylphenidate treatment.
Measured: Baseline and ~90 minutes after first dose administered
Measure key safety outcomes using the Side Effects Rating Scale (SERS)
The investigator will record all adverse effects reported by participants and categorize adverse effects by type and severity based on the Side Effects Rating Scale. The investigator will present summary statistics, including the number of participants experiencing each type of adverse effect, the severity and the overall percentage of participants affected.
Measured: Baseline in-clinic assessments followed by remote weekly assessments for 4 weeks
Measure key safety outcomes using the Systematic Assessment for Treatment Emergent Effects
The investigator will record all adverse effects reported by participants and categorize adverse effects by type and severity based on the Systematic Assessment for Treatment Emergent Effects. The investigator will present summary statistics, including the number of participants experiencing each type of adverse effect, the severity, and the overall percentage of participants affected
Measured: Baseline in-clinic assessments followed by remote weekly assessments for 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2025
- Study start25 Nov 2025
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 30 patients + 42 caregivers (including 12 caregivers who declined participation for interviews)
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew W. Heitzer, PhD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07226219
- Sponsor's protocol ID
- STARS
- Status last verified
- Sep 2026
- First submitted
- 22 Oct 2025
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No