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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odense University Hospital

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Sep 2025 → ongoing

Decision date (initial)

2025-01-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of methylphenidate to alleviate cancer-related fatigue in patients treated for a pediatric brain tumor and screened as having cancer-related fatigue

Secondary objectives 1

1. To study the effects of methylphenidate on neurocognitive variables, sleep and physical activity patterns, and quality of life in patients treated for a pediatric brain tumor and screened as having cancer-related fatigue

Conditions and MedDRA coding

Cancer-related fatigue after treatment of pediatric brain tumor

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Diagnosed and treated for a brain tumor during childhood or adolescence (0-≤18 years).
2. Treated for a brain tumor 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 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/or legal guardians 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 pediatric brain tumor compared to estimated premorbid ability, as assessed from consultations in the childhood cancer outpatient clinics.

Exclusion criteria 9

1. Any known contraindications to methylphenidate medication 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. Acceptable effective contraceptive must be used for the duration of the trial, per guidelines by the Clinical Trials Coordination Group (CTCG). 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes in patient self-reported or parent proxy-reported fatigue from baseline to week 6 of MPH or placebo treatment as measured by the PedsQL Multidimensional Fatigue Scale (MFS).

Secondary endpoints 6

1. Changes from baseline in self and parent-reported executive function measured by the BRIEF-2.
2. Changes from baseline in digital measures of sustained attention and executive function.
3. Changes from baseline in standardized neurocognitive measures of processing speed and working memory.
4. Changes from baseline in self and parent-reported measures of Health Related Quality of Life measured by the PedsQL 4.0 Generic Core Scales Module.
5. Time spent within different activity domains and sleep-wake patterns measured by actigraphy.
6. Changes from baseline in self and parent-reported side-effects measured by Barkley’s Side-Effects Rating Scale.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation

Odense University Hospital

Address

J B Winsloews Vej 4

City

Odense C

Postcode

5000

Country

Denmark

Scientific contact point

Organisation

Odense University Hospital

Contact name

Principal and coordinating investigator

Public contact point

Organisation

Odense University Hospital

Contact name

Sponsor

Third parties 2

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications