A clinical trial is testing whether the stimulant drug methylphenidate—commonly used for ADHD—can reduce the debilitating fatigue that affects most people with advanced cancer. Fatigue in advanced cancer is often severe, persistent, and poorly managed by current treatments. Standard approaches such as rest or energy conservation have limited effect, and no drug is licensed for this condition in the UK. This trial directly addresses that gap by comparing methylphenidate against a placebo in patients receiving specialist palliative care. If methylphenidate proves effective, it could offer a practical, low-cost option to improve quality of life for thousands of patients who currently have few alternatives. The drug is already widely available and familiar to clinicians, so a positive result could be implemented quickly in palliative care settings. Even a modest improvement in fatigue could meaningfully affect a patient’s ability to engage in daily activities, spend time with family, or tolerate other treatments. The trial also tracks side effects, survival, and patient satisfaction, ensuring any benefit is weighed against real-world risks. If the drug does not work, the study will still provide high-quality evidence to stop an ineffective treatment and redirect resources elsewhere.
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Design: Prospective randomised double-blind placebo-controlled trial with internal pilot Aim: Estimate clinical effectiveness of methylphenidate (MPH) vs placebo for cancer-related fatigue (CRF) in patients receiving specialist palliative care (SPC) Setting: Multi-centre study with community, day-care & outpatients Population: Patients with advanced cancer with CRF & receiving SPC Inclusions: 18+ years; advanced cancer; moderate to severe fatigue; informed consent; prognosis 2-12 months; under care of SPC Exclusions: Known contraindication to MPH; anaemia; liver failure; concomitant psycho-stimulant use Health technologies being assessed: MPH tablets 5mgs/day increasing up to maximum 60mgs/day in divided doses Outcomes: Primary outcome is fatigue at 6 weeks measured by Functional Assessment of Chronic Illness Therapy (FACIT-F). Secondary outcomes (measured at 3 & 9 weeks) are other measures of quality of life (using European Organisation for Research & Treatment of Cancer core Quality of Life Palliative Care questionnaire & the EuroQol EQ-5D 5 level [EQ-5D-5L]), adverse events, activities of daily living; appetite; satisfaction of patients & carers; survival & need for other medication. Missing data: Data are more likely to be missing when fatigue severity is greater, & may not reasonably be considered missing at random. Principal analysis will be on complete data, & we will explore the effects of missing data using developed deviance based likelihood ratio approaches Procedures: Patients will be identified by clinical teams & provided with study information. At screening, informed consent will be obtained & a specimen taken (full blood count, liver & renal function). After randomisation, face-to-face assessments will occur at weeks 3, 6 & 9 & will include; completion of outcome measures & blood pressure. Patients will be contacted by telephone weekly so that study medication can be titrated. The comparator group will receive individually titrated placebo tablets. Both groups will receive usual care Follow-up: Once participants have completed the nine week follow up they will be given the option to continue (or start) methylphenidate according to local clinical practice and circumstances. Pilot: Feasibility of recruitment strategy, randomisation & follow-up will be evaluated during a pilot at four centres during first 9 months of the study. During pilot phase (months 10-18) recruitment should exceed 70% of rate expected once trial is fully established. Sample size: With 230 randomised & 172 evaluable patients (25% attrition), this study has 90% power to detect a difference of 5-points on FACIT-F (effect size 0.5) between groups at 5% significance (two sided). Randomization will be computer generated & stratified by centre, by receipt of palliative cancer treatment, by baseline HADS depression score & by initial fatigue score >7 Timetable: Months 1–9 set-up; 10-18 internal pilot; 19–36 recruitment; 36-42 analysis, writing & dissemination Expertise: Our team includes expertise in palliative care, mental health, clinical trials, statistics & nursing
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