Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Study protocol

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

Authors: Hanneke Poort, Constans A. H. H. V. M. Verhagen, Marlies E. W. J. Peters, Martine M. Goedendorp, A. Rogier T. Donders, Maria T. E. Hopman, Maria W. G. Nijhuis-van der Sanden, Thea Berends, Gijs Bleijenberg, Hans Knoop

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

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.

Methods

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.

Discussion

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.

Trial registration

NTR3812; date of registration: 23/01/2013.
Literature
1.
Global Burden of Disease Cancer C, Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R, et al. The Global Burden of Cancer 2013. JAMA Oncol. 2015;1:505–27.CrossRef
2.
Sepulveda C, Marlin A, Yoshida T, Ullrich A. Palliative Care: the World Health Organization's global perspective. J Pain Symptom Manage. 2002;24:91–6.CrossRefPubMed
3.
Butt Z, Rosenbloom SK, Abernethy AP, Beaumont JL, Paul D, Hampton D, Jacobsen PB, Syrjala KL, Von Roenn JH, Cella D. Fatigue is the most important symptom for advanced cancer patients who have had chemotherapy. J Natl Compr Canc Netw. 2008;6:448–55.PubMedPubMedCentral
4.
Hauser K, Walsh D, Rybicki LA, Davis MP, Seyidova-Khoshknabi D. Fatigue in advanced cancer: a prospective study. Am J Hosp Palliat Care. 2008;25:372–8.CrossRefPubMed
5.
Radbruch L, Strasser F, Elsner F, Goncalves JF, Loge J, Kaasa S, Nauck F, Stone P. Research Steering Committee of the European Association for Palliative C: Fatigue in palliative care patients -- an EAPC approach. Palliat Med. 2008;22:13–32.CrossRefPubMed
6.
Echteld MA, Passchier J, Teunissen S, Claessen S, de Wit R, van der Rijt CC. Multidimensional fatigue and its correlates in hospitalised advanced cancer patients. Eur J Cancer. 2007;43:1030–6.CrossRefPubMed
7.
8.
Network NCC. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Cancer-Related Fatigue. 2016.
9.
Paiva CE, Paiva BS. Prevalence, predictors, and prognostic impact of fatigue among Brazilian outpatients with advanced cancers. Support Care Cancer. 2013;21:1053–60.CrossRefPubMed
10.
Hofman M, Ryan JL, Figueroa-Moseley CD, Jean-Pierre P, Morrow GR. Cancer-related fatigue: the scale of the problem. Oncologist. 2007;12 Suppl 1:4–10.CrossRefPubMed
11.
Tanaka K, Akechi T, Okuyama T, Nishiwaki Y, Uchitomi Y. Impact of dyspnea, pain, and fatigue on daily life activities in ambulatory patients with advanced lung cancer. J Pain Symptom Manage. 2002;23:417–23.CrossRefPubMed
12.
Peters ME, Goedendorp MM, Verhagen SA, van der Graaf WT, Bleijenberg G. Exploring the contribution of psychosocial factors to fatigue in patients with advanced incurable cancer. Psychooncology. 2014;23:773–9.CrossRefPubMed
13.
Mucke M, Mochamat, Cuhls H, Peuckmann-Post V, Minton O, Stone P, Radbruch L. Pharmacological treatments for fatigue associated with palliative care. Cochrane Database Syst Rev. 2015;5:CD006788.
14.
15.
Cramp F, Byron-Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev. 2012;11, CD006145.PubMed
16.
Lowe SS, Watanabe SM, Courneya KS. Physical activity as a supportive care intervention in palliative cancer patients: a systematic review. J Support Oncol. 2009;7:27–34.PubMed
17.
Hagelin CL, Wengstrom Y, Ahsberg E, Furst CJ. Fatigue dimensions in patients with advanced cancer in relation to time of survival and quality of life. Palliat Med. 2009;23:171–8.CrossRefPubMed
18.
Oldervoll LM, Loge JH, Paltiel H, Asp MB, Vidvei U, Wiken AN, Hjermstad MJ, Kaasa S. The effect of a physical exercise program in palliative care: A phase II study. J Pain Symptom Manage. 2006;31:421–30.CrossRefPubMed
19.
Porock D, Kristjanson LJ, Tinnelly K, Duke T, Blight J. An exercise intervention for advanced cancer patients experiencing fatigue: a pilot study. J Palliat Care. 2000;16:30–6.PubMed
20.
van den Dungen IA, Verhagen CA, van der Graaf WT, van den Berg JP, Vissers KC, Engels Y. Feasibility and impact of a physical exercise program in patients with advanced cancer: a pilot study. J Palliat Med. 2014;17:1091–8.CrossRefPubMed
21.
Jacobsen PB, Donovan KA, Vadaparampil ST, Small BJ. Systematic review and meta-analysis of psychological and activity-based interventions for cancer-related fatigue. Health Psychol. 2007;26:660–7.CrossRefPubMedPubMedCentral
22.
Kangas M, Bovbjerg DH, Montgomery GH. Cancer-related fatigue: a systematic and meta-analytic review of non-pharmacological therapies for cancer patients. Psychol Bull. 2008;134:700–41.CrossRefPubMed
23.
Gielissen MF, Verhagen S, Witjes F, Bleijenberg G. Effects of cognitive behavior therapy in severely fatigued disease-free cancer patients compared with patients waiting for cognitive behavior therapy: a randomized controlled trial. J Clin Oncol. 2006;24:4882–7.CrossRefPubMed
24.
Prinsen H, van Dijk JP, Zwarts MJ, Leer JW, Bleijenberg G, van Laarhoven HW. The role of central and peripheral muscle fatigue in postcancer fatigue: a randomized controlled trial. J Pain Symptom Manage. 2015;49:173–82.CrossRefPubMed
25.
Servaes P, Verhagen S, Bleijenberg G. Determinants of chronic fatigue in disease-free breast cancer patients: a cross-sectional study. Ann Oncol. 2002;13:589–98.CrossRefPubMed
26.
27.
Goedendorp MM, Peters ME, Gielissen MF, Witjes JA, Leer JW, Verhagen CA, Bleijenberg G. Is increasing physical activity necessary to diminish fatigue during cancer treatment? Comparing cognitive behavior therapy and a brief nursing intervention with usual care in a multicenter randomized controlled trial. Oncologist. 2010;15:1122–32.CrossRefPubMedPubMedCentral
28.
Goedendorp MM, Gielissen MF, Peters ME, Verhagen CA, Bleijenberg G. Moderators and long-term effectiveness of cognitive behaviour therapy for fatigue during cancer treatment. Psychooncology. 2012;21:877–85.CrossRefPubMed
29.
Armes J, Chalder T, Addington-Hall J, Richardson A, Hotopf M. A randomized controlled trial to evaluate the effectiveness of a brief, behaviorally oriented intervention for cancer-related fatigue. Cancer. 2007;110:1385–95.CrossRefPubMed
30.
Ream E, Richardson A, Alexander-Dann C. Supportive intervention for fatigue in patients undergoing chemotherapy: a randomized controlled trial. J Pain Symptom Manag. 2006;31:148–61.CrossRef
31.
Davis MP, Khoshknabi D, Yue GH. Management of fatigue in cancer patients. Curr Pain Headache Rep. 2006;10:260–9.CrossRefPubMed
32.
Frazier PA, Tix AP, Barron KE. Testing moderator and mediator effects in counseling psychology research. J Couns Psychol. 2004;51:115–34.CrossRef
33.
Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. Dimensional assessment of chronic fatigue syndrome. J Psychosom Res. 1994;38:383–92.CrossRefPubMed
34.
Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14:377–81.PubMed
35.
Staal JB, Hlobil H, Koke AJ, Twisk JW, Smid T, van Mechelen W. Graded activity for workers with low back pain: who benefits most and how does it work? Arthritis Rheum. 2008;59:642–9.CrossRefPubMed
36.
37.
Beurskens AJ, Bultmann U, Kant I, Vercoulen JH, Bleijenberg G, Swaen GM. Fatigue among working people: validity of a questionnaire measure. Occup Environ Med. 2000;57(5):353–7. 
38.
Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–76.CrossRefPubMed
39.
Aaronson NK, Bullinger M, Ahmedzai S. A modular approach to quality-of-life assessment in cancer clinical trials. Recent Results Cancer Res. 1988;111:231–49.CrossRefPubMed
40.
41.
Bergner M, Bobbitt RA, Carter WB, Gilson BS. The Sickness Impact Profile: development and final revision of a health status measure. Med Care. 1981;19:787–805.CrossRefPubMed
42.
de Bruin AF, de Witte LP, Stevens F, Diederiks JP. Sickness Impact Profile: the state of the art of a generic functional status measure. Soc Sci Med. 1992;35:1003–14.CrossRefPubMed
43.
Montoye HJ, Washburn R, Servais S, Ertl A, Webster JG, Nagle FJ. Estimation of energy expenditure by a portable accelerometer. Med Sci Sports Exerc. 1983;15:403–7.CrossRefPubMed
44.
Du H, Newton PJ, Salamonson Y, Carrieri-Kohlman VL, Davidson PM. A review of the six-minute walk test: its implication as a self-administered assessment tool. Eur J Cardiovasc Nurs. 2009;8:2–8.CrossRefPubMed
45.
Jacobsen PB, Andrykowski MA, Thors CL. Relationship of catastrophizing to fatigue among women receiving treatment for breast cancer. J Consult Clin Psychol. 2004;72:355–61.CrossRefPubMedPubMedCentral
46.
Borm GF, Fransen J, Lemmens WA. A simple sample size formula for analysis of covariance in randomized clinical trials. J Clin Epidemiol. 2007;60:1234–8.CrossRefPubMed
47.
Van Breukelen GJ. ANCOVA versus change from baseline: more power in randomized studies, more bias in nonrandomized studies [corrected]. J Clin Epidemiol. 2006;59:920–5.CrossRefPubMed
48.
Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods. 2008;40:879–91.CrossRefPubMed
49.
White C, Gilshenan K, Hardy J. A survey of the views of palliative care healthcare professionals towards referring cancer patients to participate in randomized controlled trials in palliative care. Support Care Cancer. 2008;16:1397–405.CrossRefPubMed
50.
Kars MC, van Thiel GJ, van der Graaf R, Moors M, de Graeff A, van Delden JJ. A systematic review of reasons for gatekeeping in palliative care research. Palliat Med. 2016;30(6):533–48.CrossRefPubMed
51.
Poort H, Peters ME, Verhagen SA, Verhoeven J, van der Graaf WT, Knoop H. Time to practice what we preach? Appreciating the autonomy of cancer patients on deciding whether they want to be informed about interventional studies for fatigue. Palliat Med. 2016;30(9):897–8.CrossRefPubMed
52.
Derogatis LR. Symptom Checklist-90-Revised. In: Handbook of psychiatric measures. Arlington: American Psychiatric Association; 2000. p. 81–4.
53.
Brom D, Kleber R. De Schok Verwerkings Lijst. Ned Tijdschr Psychol. 1985;40:164–8.
54.
Gielissen MF, Prins JB, Knoop H, Verhagen S, Bleijenberg G. Pictorial Representation of Self and Illness Measure (PRISM): a graphic instrument to assess suffering in fatigued cancer survivors. Psychol Assess. 2013;25:658–63.CrossRefPubMed
55.
Evers AW, Kraaimaat FW, van Lankveld W, Jongen PJ, Jacobs JW, Bijlsma JW. Beyond unfavorable thinking: the illness cognition questionnaire for chronic diseases. J Consult Clin Psychol. 2001;69:1026–36.CrossRefPubMed
56.
Lauwerier E, Crombez G, Van Damme S, Goubert L, Vogelaers D, Evers AW. The construct validity of the illness cognition questionnaire: the robustness of the three-factor structure across patients with chronic pain and chronic fatigue. Int J Behav Med. 2010;17:90–6.CrossRefPubMed
57.
Beck AT, Guth D, Steer RA, Ball R. Screening for major depression disorders in medical inpatients with the Beck Depression Inventory for Primary Care. Behav Res Ther. 1997;35:785–91.CrossRefPubMed
58.
Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 1983;67:361–70.CrossRefPubMed
59.
Prins JB, Bleijenberg G, Bazelmans E, Elving LD, de Boo TM, Severens JL, van der Wilt GJ, Spinhoven P, van der Meer JW. Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial. Lancet. 2001;357:841–7.CrossRefPubMed
60.
Ray C, Weir W, Stewart D, Miller P, Hyde G. Ways of Coping with Chronic Fatigue Syndrome - Development of an Illness Management Questionnaire. Soc Sci Med. 1993;37:385–91.CrossRefPubMed
61.
Timmerman IGH, Emanuels-Zuurveen ES, Emmelkamp PMG. The Social Support Inventory (SSI): A brief scale to assess perceived adequacy of social support. Clin Psychol Psychother. 2000;7:401–10.CrossRef
Metadata
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
Authors
Hanneke Poort
Constans A. H. H. V. M. Verhagen
Marlies E. W. J. Peters
Martine M. Goedendorp
A. Rogier T. Donders
Maria T. E. Hopman
Maria W. G. Nijhuis-van der Sanden
Thea Berends
Gijs Bleijenberg
Hans Knoop
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3076-0

Other articles of this Issue 1/2017

BMC Cancer 1/2017 Go to the issue

Research article

Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer

Research article

Whether intermediate-risk stage 1A, grade 1/2, endometrioid endometrial cancer patients with lesions larger than 2 cm warrant lymph node dissection?

Research article

In search of druggable targets for GBM amino acid metabolism

Research article

MALAT1 promoted invasiveness of gastric adenocarcinoma

Study protocol

Whole brain radiotherapy versus stereotactic radiosurgery for 4–10 brain metastases: a phase III randomised multicentre trial

Research article

Diagnostic accuracy of 18F–FDG PET/CT and MR imaging in patients with adenoid cystic carcinoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits