Methylphenidate for fatigue in survivors of pediatric brain tumors

Effect of Methylphenidate on Cancer-related Fatigue in Patients Treated for a Brain Tumor During Childhood or Adolescence: Protocol for a Randomized, Double-blind, Placebo-controlled Crossover Trial - the EMBRAIN Trial

This trial will test whether methylphenidate can reduce fatigue and improve thinking in children and teens who survived brain tumors.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 6 Years to 27 Years
• Sex: All
• Sponsor: Odense University Hospital (Academic / other)
• Locations: 4 sites (Aalborg and 3 other locations)
• Trial ID: NCT06905587 on ClinicalTrials.gov

What this trial studies

This Phase 3 multicenter trial in Denmark gives eligible pediatric brain tumor survivors either methylphenidate or a matching placebo to measure effects on cancer-related fatigue and cognitive function. Participants are generally aged six years and older, at least 12 months off therapy, within 10 years of diagnosis, must speak Danish for validated assessments, and must have clinically significant fatigue by the PedsQL MFS. Outcomes will be measured with validated questionnaires and cognitive tests at baseline and during follow-up to compare changes between groups. Safety monitoring for contraindications and adverse effects of methylphenidate will be performed throughout the study.

Who should consider this trial

Good fit: Children and adolescents treated for a brain tumor in childhood who are at least 6 years old, at least 12 months off therapy, within 10 years of diagnosis, Danish-speaking, and have clinically significant fatigue by PedsQL MFS.

Not a fit: Patients with contraindications to stimulants, active tumor progression, or without clinically significant fatigue per the trial criteria are unlikely to receive benefit from this intervention.

Why it matters

Potential benefit: If effective, methylphenidate could reduce debilitating fatigue and improve cognition, helping survivors better participate in daily life.

How similar studies have performed: Prior small or adult studies of methylphenidate for cancer-related fatigue have shown mixed or modest benefits, and high-quality pediatric brain tumor data are limited.

Eligibility criteria

Inclusion Criteria:

1. Diagnosed and treated for a brain tumor during childhood or adolescence (0-≤18 years).
2. Treated for a PBT during the previous 10 years, starting from date of diagnosis.
3. Aged ≥6 years 0 months at the start of the trial.
4. Off therapy/active treatment for pediatric brain tumor (PBT) for 12 months at the start of the trial.
5. No known signs of clinical or radiological tumor progression at last follow-up.
6. Danish is the sole or primary language (enabling provision of validated assessment tools).
7. Patient and family have provided consent for inclusion in the trial.
8. Clinically significant fatigue based on the PedsQL MFS questionnaire at baseline, defined by a score ≥ 1 standard deviation below the normative mean.
9. History of clinically relevant fatigue after treatment of PBT compared to estimated premorbid ability, as assessed from consultations in the childhood cancer outpatient clinics.

Exclusion Criteria:

1. Any known contraindications to methylphenidate as outlined below:

   A) Hypersensitivity to the active substance or any excipients listed in the summary of product characteristics. B) Glaucoma. C) Pheochromocytoma. D) Hyperthyroidism. E) Mania. F) Psychosis. G) Anorexia nervosa. H) Current or previous severe depression. I) Suicidal behavior. J) Poorly controlled type 1 bipolar affective disorder. K) Antisocial or borderline personality disorder. L) Pre-existing cardiovascular disorders, including severe hypertension, heart failure, arterial occlusive disease, angina pectoris, hemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening cardiac arrhythmias and channelopathies. M) Pre-existing cerebrovascular disease, cerebral aneurysm, vascular abnormalities including vasculitis or stroke. N) Treatment with irreversible MAO inhibitors within the last 14 days and reversible MAO inhibitors within the last 24 hours.
2. History of recent poorly controlled seizures.
3. Motor tics or Tourette syndrome (including family history of tic disorder).
4. Known diagnosis of Attention Deficit/Hyperactivity Disorder or Autism Spectrum Disorder.
5. Known diagnosis of Full Scale Intelligence Quotient (FSIQ) of \<50.
6. Pregnancy. Participants known to be pregnant or breastfeeding at screening/registration will not be enrolled in the trial. All sexually active women of childbearing potential (WOCBP) must have a negative pregnancy test prior to the start of treatment. Acceptableeffective contraceptive must be used for the duration of the trial. No further testing is needed during trial, unless the participant suspects to have become pregnant.
7. Concerns about family ability to safely store or administer MPH, or to report side effects appropriately/concerns about familial substance abuse.
8. Concurrent use of opiods (ATC N02A) or benzodiazepines (ATC N05BA and N05CF).
9. Simultaneously enrolled in another clinical trial investigating cancer-related fatigue with a pharmaceutical intervention.

Where this trial is running

Aalborg and 3 other locations

• Aalborg University Hospital — Aalborg, Denmark (Not_yet_recruiting)
• Aarhus University Hospital — Aarhus, Denmark (Recruiting)
• Rigshospitalet — Copenhagen, Denmark (Not_yet_recruiting)
• Odense University Hospital — Odense, Denmark (Recruiting)

Study contacts

• Study coordinator: Sebastian W Most-Mottelson, MD, PhD Student

Conditions Brain Tumor, Pediatric; Cancer-related Fatigue; Methylphenidate; methylphenidate; cancer-related fatigue; brain tumor; childhood cancer; pediatric cancer