Methylphenidate in Pediatric Brain Tumor Survivors With Cancer-related Fatigue

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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 methylphenid
• Препарат Placebo
  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).

Первичные конечные точки

• PedsQL Multidimensional Fatigue Scale (MFS) [Срок оценки: At baseline, at Week 6, Week 16, and Week 20 (follow-up).]

Вторичные конечные точки (8)

• PedsQL Multidimensional Fatigue Scale (MFS) [Срок оценки: At baseline, at Week 6, Week 16, and Week 20 (follow-up).]
• Behaviour Rating Inventory of Executive Function (BRIEF) [Срок оценки: At baseline, at Week 6, and Week 16.]
• Connor's Continuous Performance Test (CPT) Online Suite [Срок оценки: At baseline, at Week 6, and Week 16.]
• Wechsler Coding [Срок оценки: At baseline, at Week 6, and Week 16.]
• Wechsler Digit Span [Срок оценки: At baseline, at Week 6, and Week 16.]
• PedsQL Generic Core Scales [Срок оценки: At baseline, at Week 6, and Week 16.]
• Accelerometry (Axivity AX3) [Срок оценки: 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) [Срок оценки: 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)..]

Критерии участия

Критерии включения

• Diagnosed and treated for a brain tumor during childhood or adolescence (0-≤18 years).
• Treated for a PBT during the previous 10 years, starting from date of diagnosis.
• Aged ≥6 years 0 months 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).
• 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.

Критерии исключения

• 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.

• History of recent poorly controlled seizures.
• Motor 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Дания · 4 центра

• Aalborg University Hospital — Aalborg
• Aarhus University Hospital — Aarhus
• Rigshospitalet — Copenhagen
• Odense University Hospital — Odense

Идентификаторы

NCT: NCT06905587 · 24/51848 · R352-A20781 · 2023-001094 · 2023-507926-18-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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