Physiological and neurophysiological determinants of postcancer fatigue: design of a randomized controlled trial

BACKGROUND: Postcancer fatigue is a frequently occurring, severe, and invalidating problem, impairing quality of life. Although it is possible to effectively treat postcancer fatigue with cognitive behaviour therapy, the nature of the underlying (neuro)physiology of postcancer fatigue remains unclear. Physiological aspects of fatigue include peripheral fatigue, originating in muscle or the neuromuscular junction; central fatigue, originating in nerves, spinal cord, and brain; and physical deconditioning, resulting from a decreased cardiopulmonary function. Studies on physiological aspects of postcancer fatigue mainly concentrate on deconditioning. Peripheral and central fatigue and brain morphology and function have been studied for patients with fatigue in the context of chronic fatigue syndrome and neuromuscular diseases and show several characteristic differences with healthy controls. METHODS/DESIGN: Fifty seven severely fatigued and 21 non-fatigued cancer survivors will be recruited from the Radboud University Nijmegen Medical Centre. Participants should have completed treatment of a malignant, solid tumour minimal one year earlier and should have no evidence of disease recurrence. Severely fatigued patients are randomly assigned to either the intervention condition (cognitive behaviour therapy) or the waiting list condition (start cognitive behaviour therapy after 6 months). All participants are assessed at baseline and the severely fatigued patients also after 6 months follow-up (at the end of cognitive behaviour therapy or waiting list). Primary outcome measures are fatigue severity, central and peripheral fatigue, brain morphology and function, and physical condition and activity. DISCUSSION: This study will be the first randomized controlled trial that characterizes (neuro)physiological factors of fatigue in disease-free cancer survivors and evaluates to which extent these factors can be influenced by cognitive behaviour therapy. The results of this study are not only essential for a theoretical understanding of this invalidating condition, but also for providing an objective biological marker for fatigue that could support the diagnosis and follow-up of treatment. TRIAL REGISTRATION: The study is registered at http://ClinicalTrials.gov (NCT01096641).