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

St. Jude Children's Research Hospital

Status and phase: Enrolling; Phase 1

Conditions: Cognitive Impairment; Sickle Cell Disease; Attention Deficit/Hyperactivity Disorder (ADHD); Executive Dysfunction

Treatments: Drug: Extended-Release Methylphenidate

Study type: Interventional

Funder types: Other

Identifiers

NCT07226219

STARS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 72 estimated patients

Sex: All

Ages: 8 to 17 years old

Volunteers: No Healthy Volunteers

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 or rating scale criteria met:

• *Score 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 above the 84th percentile on any 1 out of 2 parent rating scales:

  • BRIEF-2 Global Executive
  • BASC-3 Attention

• 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

• Uncontrolled or untreated hypertension

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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72 participants in 1 patient group

Methylphenidate Treatment Group

Experimental group

Description:

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.

Treatment:

Drug: Extended-Release Methylphenidate