Methylphenidate to Address Attention and Executive Deficits Among Children With Sickle Cell Disease

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.

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 parents.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Sickle Cell Disease; Executive Dysfunction; Attention Deficit/Hyperactivity Disorder (ADHD)
• Intervention / Treatment: Drug: Extended-Release Methylphenidate

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. Parents will complete rating scales and interviews to assess treatment acceptability and decision-making.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Andrew Heitzer, PhD; Phone Number: 888-226-4343; Email: referralinfo@stjude.org

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • St. Jude Children's Research Hospital
      • Principal Investigator: Andrew K Heitzer, PhD
      • Contact: Andrew Heitzer, PhD; Phone Number: 888-226-4343; Email: referralinfo@stjude.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with SCD of any genotype
• 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 the 16th percentile on any 2 out of 4 performance measures:

  • NIH Toolbox Flanker
  • 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 the 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 parent willing to participate and provide consent/assent according to institutional guidelines
• Negative pregnancy test

Exclusion Criteria:

• Primary language other than English
• Score below the 2nd percentile on the Wechsler Abbreviated Scale of Intelligence (WASI)-2 intelligence quotient (IQ) test
• 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
• 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.

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylphenidate Treatment Group; 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.	Drug: Extended-Release Methylphenidate; 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.; Other Names: MPH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess feasibility of methylphenidate	Feasibility is measured by the participation rate (i.e., ratio of those who agree to participate to those approached).	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).	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.	Adherence is measured on a weekly basis through 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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	Baseline in-clinic assessments followed by remote weekly assessments for 4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate decision-making and determinants influencing methylphenidate utilization among parents	Semi-structured interviews will be conducted. The interviews will be transcribed and qualitatively coded.	Baseline and 4-6 weeks after treatment

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Andrew W. Heitzer, PhD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: October 22, 2025
• First Submitted That Met QC Criteria: November 6, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: ADHD; SCD
• Additional Relevant MeSH Terms: Mental Disorders; Genetic Diseases, Inborn; Neurocognitive Disorders; Hematologic Diseases; Cognition Disorders; Neurodevelopmental Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Attention Deficit and Disruptive Behavior Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Cognitive Dysfunction; Anemia, Sickle Cell; Attention Deficit Disorder with Hyperactivity; 5,10-dihydro-5-methylphenazine
• Other Study ID Numbers: STARS (STaRS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No