Brain Tumor, PediatricPhase 3EMBRAINNCT06905587
Methylphenidate in Pediatric Brain Tumor Survivors With Cancer-related Fatigue
A Phase 3 study testing Methylphenidate (MPH) in people with Brain Tumor, Pediatric and Cancer-related Fatigue, run by Odense University Hospital at 4 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 27 years
- Conditions the study is for
- Brain Tumor, Pediatric, Cancer-related Fatigue, Methylphenidate
- What is being tested?
- Methylphenidate (MPH)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 4 sitesDenmark
- Study dates
- 2 Sep 2025to Dec 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 27 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosed and treated for a brain tumor during childhood or adolescence (0-≤18 years).
- Treated for a brain tumor during the previous 10 years.
- Age ≥6 years and <28 years at the start of the trial.
- Off therapy/active treatment for pediatric brain tumor (PBT) for 12 months at the start of the trial.
- No known signs of clinical or radiological tumor progression at last follow-up.
- Danish is the sole or primary language (enabling provision of validated assessment tools).
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- Patient and family have provided consent for inclusion in the trial.
- Clinically significant fatigue based on the PedsQL MFS questionnaire at baseline, defined by a score ≥ 1 standard deviation below the normative mean.
- History of clinically relevant fatigue after treatment of PBT compared to estimated premorbid ability, as assessed from consultations in the childhood cancer outpatient clinics.
Who cannot join
- Any known contraindications to methylphenidate as outlined below:
- 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.
- History of recent poorly controlled seizures.
- Complex tics or Tourette syndrome (including family history of tic disorder).
- Known diagnosis of Attention Deficit/Hyperactivity Disorder or Autism Spectrum Disorder.
- Known diagnosis of Full Scale Intelligence Quotient (FSIQ) of <50.
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- 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.
- Concerns about family ability to safely store or administer MPH, or to report side effects appropriately/concerns about familial substance abuse.
- Concurrent use of opiods (ATC N02A) or benzodiazepines (ATC N05BA and N05CF).
- Simultaneously enrolled in another clinical trial investigating cancer-related fatigue with a pharmaceutical intervention.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Sebastian W Most-Mottelson, MD, PhD Student contact
Denmark4 sites, 4 recruiting
- Recruiting
Aalborg University Hospital
Aalborg, 9000
Christina Friis Jensen, Consultant, MD, +45 97663368, cfj@rn.dk
Christina Friis Jensen, Consultant, MD
- Recruiting
Aarhus University Hospital
Aarhus, 8200
Louise T Henriksen, MD, PhD, +45 20921611, louhen@rm.dk
Louise T Henriksen, MD, PhD
- Recruiting
Rigshospitalet
Copenhagen, 2100
Christine Dahl, Consultant, MD, PhD, +45 35454137, christine.dahl@regionh.dk
Christine Dahl, Consultant, MD, PhD
- Recruiting
Odense University Hospital
Odense, 5000
Mathias Rathe, Consultant, MD, PhD, +45 20469682, mathias.rathe@rsyd.dk
Sebastian W Most-Mottelson, MD, PhD Student
About this study
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
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.
- Being tested
- Methylphenidate (MPH), Placebo
- 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
- Medical subject headings
- Brain Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylphenidate (MPH)Drug
10 mg methylphenidate tablets with a scoreline. Tablets will be administered orally.
For children aged 6-12, a daily dose of 5 mg x 2 will be administered during the first week with an increase in dose to 10 mg x 2 in the second week. For adolescents and adults above 12 years of age, the same starting dose will be used as for children, with weekly incremental increases up to a maximum of 15 mg x 2 daily in the third week. In case of potential toxicity events during study, dosage of methylphenidate can be modified according to protocol.
PlaceboDrug
10 mg methylphenidate-matched placebo tablets with a scoreline. Tablets will be administered orally.
Dosage will follow the exact same principles as for the study drug (methylphenidate).
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate, Then Placebo | Experimental | Patients will receive treatment with methylphenidate tablets for 6 weeks, and then cross over to treatment with methylphenidate-matched placebo tablets for an additional 6 weeks. A four week wash out period is incorporated between treatments. Receives: Drug: Methylphenidate (MPH); Drug: Placebo |
| Placebo, Then Methylphenidate | Experimental | Patients will receive treatment with methylphenidate-matched placebo tablets for 6 weeks, and then cross over to treatment with methylphenidate tablets for an additional 6 weeks. A four week wash out period is incorporated between treatments. Receives: Drug: Methylphenidate (MPH); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PedsQL Multidimensional Fatigue Scale (MFS)
Changes in patient self-reported fatigue (participants above 18 years of age) or parent proxy-reported fatigue (participants between 6-17 years of age) from baseline to week 6 of MPH or placebo treatment as measured by the PedsQL Multidimensional Fatigue Scale (MFS).
Measured: At baseline, at Week 6, Week 16, and Week 20 (follow-up).
Secondary outcomes (8)
PedsQL Multidimensional Fatigue Scale (MFS)
Changes from baseline in self-reported fatigue (participants aged 6-17 years of age) measured by the PedsQL MFS.
Measured: At baseline, at Week 6, Week 16, and Week 20 (follow-up).
Behaviour Rating Inventory of Executive Function (BRIEF)
Changes from baseline in self and parent-reported executive function measured by the BRIEF-2 or BRIEF-V questionnaire.
Measured: At baseline, at Week 6, and Week 16.
Connor's Continuous Performance Test (CPT) Online Suite
Changes from baseline in digital measures of sustained attention and executive function. CPT-3 and K-CPT-2 will be used.
Measured: At baseline, at Week 6, and Week 16.
Wechsler Coding
Changes from baseline in processing speed. Coding module from Wechsler Intelligence Scale for Children Fifth Edition (WISC-V) or Wechsler Adult Intelligence Scale Fifth Edition (WAIS-V) depending on age of participant.
Measured: At baseline, at Week 6, and Week 16.
Wechsler Digit Span
Changes from baseline in working memory. Coding module from WISC-V or WAIS-V depending on age of participant.
Measured: At baseline, at Week 6, and Week 16.
PedsQL Generic Core Scales
Changes from baseline in self and parent-reported measures of Health Related Quality of Life.
Measured: At baseline, at Week 6, and Week 16.
Accelerometry (Axivity AX3)
Time spent within different activity domains and sleep-wake patterns measured by accelerometry. Axivity AX3 accelerometers will be used.
Measured: Accelerometry will be performed for a duration of 1 week during week 4-6 and week 14-16 during the study arm.
Barkley's Stimulant Side Effect Rating Scale (SSERS)
Changes from baseline in self and parent-reported side-effects. A modified version of SSERS with 21 items customized to Danish practice will be used.
Measured: 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)..
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2025
- Study start2 Sep 2025
- Primary completionDec 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Tumor, PediatricStudies of the same condition, open and under way.
- More trials run by Odense University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital Skejby, Aalborg University Hospital, Copenhagen University Hospital, Rigshospitalet, University of Southern Denmark
- Responsible party
- Sponsor
- Investigators
- Mathias Rathe, Consultant, MD, PhD, Study director, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06905587
- Sponsor's protocol ID
- 24/51848
- Other IDs
- R352-A20781, 2023-001094, 2023-507926-18-00, 2023
- Acronym
- EMBRAIN
- Status last verified
- Oct 2026
- First submitted
- 27 Nov 2024
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06905587
- Acronym / sponsor ID
- EMBRAIN / 24/51848
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Collaborators
- Aarhus University Hospital Skejby, Aalborg University Hospital, Copenhagen University Hospital, Rigshospitalet, University of Southern Denmark
- Study start
- 2 Sep 2025 (actual)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 1 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate, Then Placebo | Experimental | Drug: Methylphenidate (MPH), Drug: PlaceboPatients will receive treatment with methylphenidate tablets for 6 weeks, and then cross over to treatment with methylphenidate-matched placebo tablets for an additional 6 weeks. A four week wash out period is incorporated between treatments. |
| Placebo, Then Methylphenidate | Experimental | Drug: Methylphenidate (MPH), Drug: PlaceboPatients will receive treatment with methylphenidate-matched placebo tablets for 6 weeks, and then cross over to treatment with methylphenidate tablets for an additional 6 weeks. A four week wash out period is incorporated between treatments. |
Who may qualify
- Ages
- 6 to 27 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Diagnosed and treated for a brain tumor during childhood or adolescence (0-≤18 years).
- Treated for a brain tumor during the previous 10 years.
- Age ≥6 years and <28 years at the start of the trial.
- Off therapy/active treatment for pediatric brain tumor (PBT) for 12 months at the start of the trial.
- No known signs of clinical or radiological tumor progression at last follow-up.
Key exclusion criteria (10 listed)
- Any known contraindications to methylphenidate as outlined below:
- History of recent poorly controlled seizures.
- Complex tics or Tourette syndrome (including family history of tic disorder).
- Known diagnosis of Attention Deficit/Hyperactivity Disorder or Autism Spectrum Disorder.
- Known diagnosis of Full Scale Intelligence Quotient (FSIQ) of <50.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylphenidate (MPH)10 mg methylphenidate tablets with a scoreline. Tablets will be administered orally. For children aged 6-12, a daily dose of 5 mg x 2 will be administered during the first week with an increase in dose to 10 mg x 2 in the second week. For adolescents and adults above 12 years of age, the same starting dose will be used as for children, with weekly incremental increases up to a maximum of 15 mg x 2 daily in the third week. In case of potential toxicity events during study, dosage of methylphenidate can be modified according to protocol. | Drug | Methylphenidate, Then Placebo, Placebo, Then Methylphenidate |
| Placebo10 mg methylphenidate-matched placebo tablets with a scoreline. Tablets will be administered orally. Dosage will follow the exact same principles as for the study drug (methylphenidate). | Drug | Methylphenidate, Then Placebo, Placebo, Then Methylphenidate |
Primary outcome
PedsQL Multidimensional Fatigue Scale (MFS)
Time frame: At baseline, at Week 6, Week 16, and Week 20 (follow-up).
Changes in patient self-reported fatigue (participants above 18 years of age) or parent proxy-reported fatigue (participants between 6-17 years of age) from baseline to week 6 of MPH or placebo treatment as measured by the PedsQL Multidimensional Fatigue Scale (MFS).
8 secondary outcomes
PedsQL Multidimensional Fatigue Scale (MFS)
Time frame: At baseline, at Week 6, Week 16, and Week 20 (follow-up).
Behaviour Rating Inventory of Executive Function (BRIEF)
Time frame: At baseline, at Week 6, and Week 16.
Connor's Continuous Performance Test (CPT) Online Suite
Time frame: At baseline, at Week 6, and Week 16.
Wechsler Coding
Time frame: At baseline, at Week 6, and Week 16.
Wechsler Digit Span
Time frame: At baseline, at Week 6, and Week 16.
PedsQL Generic Core Scales
Time frame: At baseline, at Week 6, and Week 16.
Accelerometry (Axivity AX3)
Time frame: Accelerometry will be performed for a duration of 1 week during week 4-6 and week 14-16 during the study arm.
Barkley's Stimulant Side Effect Rating Scale (SSERS)
Time frame: 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)..
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sebastian W Most-Mottelson, MD, PhD Student contact
Mathias Rathe, Consultant, MD, PhD study director
Odense University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methylphenidate (MPH) in people with Brain Tumor, Pediatric and Cancer-related Fatigue, run by Odense University Hospital at 4 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sebastian W Most-Mottelson, MD, PhD Student (+45 21567257, sebastian.wenzel.most-mottelson@rsyd.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PedsQL Multidimensional Fatigue Scale (MFS) (time frame: At baseline, at Week 6, Week 16, and Week 20 (follow-up).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.