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

Official title

Pilot Trial of Stimulant Treatment to Address Attention and Executive Deficits Among Children With Sickle Cell Disease

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Assess feasibility of methylphenidate [Time frame: Feasibility is measured during the initial recruitment process for each participant.]
• Assess acceptability of methylphenidate [Time frame: Acceptability ratings are captured at baseline and after 4 weeks of treatment with methylphenidate.]
• Assess adherence to methylphenidate [Time frame: Adherence is measured on a weekly basis through 4 weeks of treatment]

Secondary outcome measures (9)

• Behavior Assessment System for Children, 3rd Edition (BASC-3), Parent Report [Time frame: Baseline and 4-6 weeks after treatment]
• Behavior Rating Inventory of Executive Function, 2nd Edition (BRIEF-2), Parent Report [Time frame: Baseline and 4-6 weeks after treatment]
• Pediatric Quality of Life Inventory (PedsQL) Sickle Cell Disease modules, Parent Report [Time frame: Baseline and 4-6 weeks after treatment]
• Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue modules, Parent Report [Time frame: Baseline and 4-6 weeks after treatment]
• Conners 4th Edition Short Form, Self Report [Time frame: Baseline and 4-6 weeks after treatment]
• NIH Toolbox Cognition [Time frame: Baseline and ~90 minutes after first dose administered]
• Woodcock Johnson Tests of Academic Achievement, 4th Edition (WJ-IV) [Time frame: Baseline and ~90 minutes after first dose administered]
• Measure key safety outcomes using the Side Effects Rating Scale (SERS) [Time frame: Baseline in-clinic assessments followed by remote weekly assessments for 4 weeks]
• Measure key safety outcomes using the Systematic Assessment for Treatment Emergent Effects [Time frame: Baseline in-clinic assessments followed by remote weekly assessments for 4 weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• St. Jude Children's Research Hospital — Memphis

Identifiers

NCT: NCT07226219 · STARS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗