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

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.

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