Clinical trial NCT06905587: Methylphenidate in Pediatric Brain Tumor Survivors With Cancer-related Fatigue
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Brain Tumor, Pediatric
Cancer-related Fatigue
Methylphenidate
Keywords: methylphenidate
cancer-related fatigue
brain tumor
childhood cancer
pediatric cancer
childhood cancer survivor
late effect
long-term effects secondary to cancer therapy in children
long-term effects of cancer-treatment
pediatric brain tumor
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital Skejby
name: Aalborg University Hospital
name: Rigshospitalet, Denmark
name: University of Southern Denmark
First posted: 2025-04-01
Enrollment: 50
Sex: ALL
Minimum age (years): 6
Maximum age (years): 27
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Cancer-related fatigue is a common and debilitating late effect in pediatric brain tumor survivors. Currently, evidence-based recommendations to ameliorate this condition are lacking.

The researchers will investigate the ability of methylphenidate to improve fatigue and cognition in pediatric brain tumor survivors suffering from cancer-related fatigue. Methylphenidate is a drug (central nervous stimulant) most commonly used in the treatment of hyperkinetic disorders such as attention-deficit/hyperactivity disorder (ADHD).

If methylphenidate shows an effect, the prospects are important for this patient group, since methylphenidate may then be included as part of the treatment of brain tumor-related fatigue.


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.

Primary outcomes:
measure: PedsQL Multidimensional Fatigue Scale (MFS)
timeFrame: At baseline, at Week 6, Week 16, and Week 20 (follow-up).
Secondary outcomes:
measure: PedsQL Multidimensional Fatigue Scale (MFS)
timeFrame: At baseline, at Week 6, Week 16, and Week 20 (follow-up).
measure: Behaviour Rating Inventory of Executive Function (BRIEF)
timeFrame: At baseline, at Week 6, and Week 16.
measure: Connor's Continuous Performance Test (CPT) Online Suite
timeFrame: At baseline, at Week 6, and Week 16.
measure: Wechsler Coding
timeFrame: At baseline, at Week 6, and Week 16.
measure: Wechsler Digit Span
timeFrame: At baseline, at Week 6, and Week 16.
measure: PedsQL Generic Core Scales
timeFrame: At baseline, at Week 6, and Week 16.
measure: Accelerometry (Axivity AX3)
timeFrame: Accelerometry will be performed for a duration of 1 week during week 4-6 and week 14-16 during the study arm.
measure: Barkley's Stimulant Side Effect Rating Scale (SSERS)
timeFrame: At baseline, Week 2, Week 3, Week 4, Week 6, Week 10, Week 12, Week 13, Week 14, Week 16, and Week 20 (follow-up)..
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Odense University Hospital
name: Mathias Rathe, Consultant, MD, PhD
role: STUDY_DIRECTOR
References: