title: Study protocol of the TIRED study: a randomised controlled trial comparing either graded exercise therapy for severe fatigue or cognitive behaviour therapy with usual care in patients with incurable cancer.
abstract: Fatigue is a common and debilitating symptom for patients with incurable cancer receiving systemic treatment with palliative intent. There is evidence that non-pharmacological interventions such as graded exercise therapy (GET) or cognitive behaviour therapy (CBT) reduce cancer-related fatigue in disease-free cancer patients and in patients receiving treatment with curative intent. These interventions may also result in a reduction of fatigue in patients receiving treatment with palliative intent, by improving physical fitness (GET) or changing fatigue-related cognitions and behaviour (CBT). The primary aim of our study is to assess the efficacy of GET or CBT compared to usual care (UC) in reducing fatigue in patients with incurable cancer.
  
  
  
  The TIRED study is a multicentre three-armed randomised controlled trial (RCT) for incurable cancer patients receiving systemic treatment with palliative intent. Participants will be randomised to GET, CBT, or UC. In addition to UC, the GET group will participate in a 12-week supervised exercise programme. The CBT group will receive a 12-week CBT intervention in addition to UC. Primary and secondary outcome measures will be assessed at baseline, post-intervention (14 weeks), and at follow-up assessments (18 and 26 weeks post-randomisation). The primary outcome measure is fatigue severity (Checklist Individual Strength subscale fatigue severity). Secondary outcome measures are fatigue (EORTC-QLQ-C30 subscale fatigue), functional impairments (Sickness Impact Profile total score, EORTC-QLQ-C30 subscale emotional functioning, subscale physical functioning) and quality of life (EORTC-QLQ-C30 subscale QoL). Outcomes at 14 weeks (primary endpoint) of either treatment arm will be compared to those of UC participants. In addition, outcomes at 18 and 26 weeks (follow-up assessments) of either treatment arm will be compared to those of UC participants.
  
  
  
  To our knowledge, the TIRED study is the first RCT investigating the efficacy of GET and CBT on reducing fatigue during treatment with palliative intent in incurable cancer patients. The results of this study will provide information about the possibility and efficacy of GET and CBT for severely fatigued incurable cancer patients.
  
  
  
  NTR3812 ; date of registration: 23/01/2013.
authors.affiliation: Expert Center for Chronic Fatigue, Radboud university medical center, Nijmegen, The Netherlands. Hanneke.Poort@radboudumc.nl.
authors.forename: Hanneke
authors.identifier: 0000-0002-1196-699X
authors.initials: H
authors.lastname: Poort
authors.affiliation: Department of Medical Oncology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Constans A H H V M
authors.initials: CA
authors.lastname: Verhagen
authors.affiliation: Department of Medical Oncology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Marlies E W J
authors.initials: ME
authors.lastname: Peters
authors.affiliation: Department of Health Psychology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Martine M
authors.initials: MM
authors.lastname: Goedendorp
authors.affiliation: Department of Health Evidence, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: A Rogier T
authors.initials: AR
authors.lastname: Donders
authors.affiliation: Department of Physiology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Maria T E
authors.initials: MT
authors.lastname: Hopman
authors.affiliation: Institute for Health Sciences, IQ Healthcare, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Maria W G
authors.initials: MW
authors.lastname: Nijhuis-van der Sanden
authors.affiliation: Expert Center for Chronic Fatigue, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Thea
authors.initials: T
authors.lastname: Berends
authors.affiliation: Expert Center for Chronic Fatigue, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Gijs
authors.initials: G
authors.lastname: Bleijenberg
authors.affiliation: Department of Medical Psychology, Amsterdam Public Health research institute, Academic Medical Centre (AMC), University of Amsterdam, Amsterdam, The Netherlands.|Expert Center for Chronic Fatigue, Department of Medical Psychology, Amsterdam Public Health research institute, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Knoop
mesh_terms: D015928:Cognitive Behavioral Therapy / Q000379:methods*; D005081:Exercise Therapy / Q000379:methods*; D005221:Fatigue / Q000209:etiology / Q000523:psychology* / Q000534:rehabilitation*; D005260:Female; D006801:Humans; D020407:Internet; D008297:Male; D009369:Neoplasms / Q000150:complications*; D010166:Palliative Care; D010809:Physical Fitness; D011788:Quality of Life / Q000523:psychology; D012720:Severity of Illness Index; D018434:Sickness Impact Profile; D016896:Treatment Outcome
keywords: Advanced cancer; Cognitive behaviour therapy; Fatigue; Graded exercise therapy; Randomised controlled trial