Light therapy as a treatment of cancer-related fatigue in (non-)Hodgkin lymphoma survivors (SPARKLE trial): study protocol of a multicenter randomized controlled trial

Daniëlle E J Starreveld, Laurien A Daniels, Heiddis B Valdimarsdottir, William H Redd, Jessie L de Geus, Sonia Ancoli-Israel, Susan Lutgendorf, Catharina M Korse, Jacobien M Kieffer, Flora E van Leeuwen, Eveline M A Bleiker, Daniëlle E J Starreveld, Laurien A Daniels, Heiddis B Valdimarsdottir, William H Redd, Jessie L de Geus, Sonia Ancoli-Israel, Susan Lutgendorf, Catharina M Korse, Jacobien M Kieffer, Flora E van Leeuwen, Eveline M A Bleiker

Abstract

Background: Cancer related fatigue (CRF) is one of the most prevalent and distressing long-term complaints reported by (non-) Hodgkin survivors. To date there has been no standard treatment for CRF in this population. A novel and promising approach to treat CRF is exposure to bright white light therapy. Yet, large scale randomized controlled trials testing its efficacy in these patients and research on potential mechanisms is lacking. The objective of the current study is to investigate the efficacy of light therapy as a treatment for CRF and to explore potential mechanisms.

Methods/design: In a multicenter, randomized controlled trial we are evaluating the efficacy of two intensities of light therapy in reducing CRF complaints and restrictions caused by CRF in survivors of Hodgkin lymphoma or diffuse large B-cell lymphoma. Secondary outcomes include sleep quality, depression, anxiety, quality of life, cognitive complaints, cancer worries, fatigue catastrophizing, self-efficacy to handle fatigue, biological circadian rhythms of melatonin, cortisol and activity, and biomarkers of inflammation. We will recruit 128 survivors, with fatigue complaints, from academic and general hospitals. Survivors are randomized to either an intervention (exposure to bright white light) or a comparison group (exposure to dim white light). The longitudinal design includes four measurement points at baseline (T0), post-intervention at 3.5 weeks (T1), 3 months post-intervention (T2) and 9 months post-intervention (T3). Each measurement point includes self-reported questionnaires and actigraphy (10 days). T0 and T1 measurements also include collection of blood and saliva samples.

Discussion: Light therapy has the potential to be an effective treatment for CRF in cancer survivors. This study will provide insights on its efficacy and potential mechanisms. If proven to be effective, light therapy will provide an easy to deliver, low-cost and low-burden intervention, introducing a new era in the treatment of CRF.

Trial registration: The study is registered at ClinicalTrials.gov on August 8th 2017( NCT03242902 ).

Keywords: Cancer related fatigue; Circadian rhythms; Hematology; Light therapy; Randomized controlled trial; Sleep quality.

Conflict of interest statement

Ethics approval and consent to participate

This study (NL 61017.031.17) has received ethical approval from the Institutional Review Board of The Netherlands Cancer Institute (METC-AVL), reference number M17SPA) on May 9th 2017 as a multi-center study. Amendments are changes made to the research after approval by the accredited METC has been given. All amendments will be notified to the METC that gave approval.

Participating hospitals are Admiraal de Ruyter hospital (Goes), Albert Schweitzer hospital (Dordrecht), Erasmus Medical Center (Rotterdam), Haga Hospital (The Hague), Leiden University Medical Center (Leiden), Radboud University Medical Center (Nijmegen), The Netherlands Cancer Institute (Amsterdam), University Medical Center Utrecht (Utrecht), VU University Medical Center (Amsterdam).

A written informed consent is obtained from all participants upon participation.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Overview of the trial design
Fig. 2
Fig. 2
Overview of study procedure

References

    1. Favier O, Heutte N, Stamatoullas-Bastard A, Carde P, van't Veer MB, Aleman BM, Noordijk EM, Thomas J, Fermé C, Henry-Amar M, et al. Survival after Hodgkin lymphoma. Cancer. 2009;115(8):1680–1691. doi: 10.1002/cncr.24178.
    1. Pfreundschuh M, Trümper L, Österborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani P-L. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera international trial (MInT) group. Lancet Oncol. 2006;7(5):379–391. doi: 10.1016/S1470-2045(06)70664-7.
    1. Aleman BM, van Leeuwen FE. Are we improving the long-term burden of Hodgkin's lymphoma patients with modern treatment? Hematol Oncol Clin North Am. 2007;21(5):961–975. doi: 10.1016/j.hoc.2007.07.005.
    1. Mock V, Atkinson A, Barsevick A, Cella D, Cimprich B, Cleeland C, Donnelly J, Eisenberger M, Escalante C, Hinds P. NCCN practice guidelines for Cancer-related fatigue. Oncology (Williston Park, NY) 2000;14(11A):151–161.
    1. Bower JE, Bak K, Berger A, Breitbart W, Escalante CP, Ganz PA, Schnipper HH, Lacchetti C, Ligibel JA, Lyman GH. Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical oncology clinical practice guideline adaptation. J Clin Oncol. 2014;32(17):1840–1850. doi: 10.1200/JCO.2013.53.4495.
    1. Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, Johnson DH, Miaskowski C, Scherr SL, Portenoy RK. Impact of cancer-related fatigue on the lives of patients: new findings from the fatigue coalition. Oncologist. 2000;5(5):353–360. doi: 10.1634/theoncologist.5-5-353.
    1. Oerlemans S, Mols F, Issa DE, Pruijt J, Peters WG, Lybeert M, Zijlstra W, Coebergh JWW, van de Poll-Franse LV. A high level of fatigue among long-term survivors of non-Hodgkin’s lymphoma: results from the longitudinal population-based PROFILES registry in the south of the Netherlands. Haematologica. 2013;98(3):479–486. doi: 10.3324/haematol.2012.064907.
    1. Daniëls L, Oerlemans S, Krol A, Creutzberg C, van de Poll-Franse L. Chronic fatigue in Hodgkin lymphoma survivors and associations with anxiety, depression and comorbidity. Br J Cancer. 2014;110(4):868–874. doi: 10.1038/bjc.2013.779.
    1. Burnham TR, Wilcox A. Effects of exercise on physiological and psychological variables in cancer survivors. Med Sci Sports Exerc. 2002;34(12):1863–1867. doi: 10.1097/00005768-200212000-00001.
    1. Milne HM, Wallman KE, Gordon S, Courneya KS. Impact of a combined resistance and aerobic exercise program on motivational variables in breast cancer survivors: a randomized controlled trial. Ann Behav Med. 2008;36(2):158–166. doi: 10.1007/s12160-008-9059-2.
    1. 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(30):4882–4887. doi: 10.1200/JCO.2006.06.8270.
    1. Montgomery GH, Kangas M, David D, Hallquist MN, Green S, Bovbjerg DH, Schnur JB. Fatigue during breast cancer radiotherapy: an initial randomized study of cognitive–behavioral therapy plus hypnosis. Health Psychol. 2009;28(3):317. doi: 10.1037/a0013582.
    1. Gielissen M, Verhagen C, Bleijenberg G. Cognitive behaviour therapy for fatigued cancer survivors: long-term follow-up. Br J Cancer. 2007;97(5):612–618. doi: 10.1038/sj.bjc.6603899.
    1. Craike MJ, Hose K, Courneya KS, Harrison SJ, Livingston PM. Perceived benefits and barriers to exercise for recently treated patients with multiple myeloma: a qualitative study. BMC Cancer. 2013;13(1):1. doi: 10.1186/1471-2407-13-319.
    1. Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Davenport Y, Mueller PS, Newsome DA, Wehr TA. Seasonal affective disorder: a description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry. 1984;41(1):72–80. doi: 10.1001/archpsyc.1984.01790120076010.
    1. Pail G, Huf W, Pjrek E, Winkler D, Willeit M, Praschak-Rieder N, Kasper S. Bright-light therapy in the treatment of mood disorders. Neuropsychobiology. 2011;64(3):152–162. doi: 10.1159/000328950.
    1. Terman M, Terman JS. Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects. CNS Spectrums. 2005;10(08):647–663. doi: 10.1017/S1092852900019611.
    1. Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM, Suppes T, Wisner KL, Nemeroff CB. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. 2005;162(4):656–662. doi: 10.1176/appi.ajp.162.4.656.
    1. Mårtensson B, Pettersson A, Berglund L, Ekselius L. Bright white light therapy in depression: a critical review of the evidence. J Affect Disord. 2015;182:1–7. doi: 10.1016/j.jad.2015.04.013.
    1. Åkerstedt T, Landström U, Byström M, Nordström B, Wibom R. Bright light as a sleepiness prophylactic: a laboratory study of subjective ratings and EEG. Percept Mot Skills. 2003;97(3):811–819. doi: 10.2466/pms.2003.97.3.811.
    1. van Maanen A, Meijer AM, van der Heijden KB, Oort FJ. The effects of light therapy on sleep problems: a systematic review and meta-analysis. Sleep Med Rev. 2016;29:52–62. doi: 10.1016/j.smrv.2015.08.009.
    1. Ancoli-Israel S, Rissling M, Neikrug A, Trofimenko V, Natarajan L, Parker BA, Lawton S, Desan P, Liu L. Light treatment prevents fatigue in women undergoing chemotherapy for breast cancer. Support Care Cancer. 2012;20(6):1211–1219. doi: 10.1007/s00520-011-1203-z.
    1. Redd WH, Valdimarsdottir H, Wu LM, Winkel G, Byrne EE, Beltre MA, Liebman ES, Erazo T, Hayes JA, Isola L. Systematic light exposure in the treatment of cancer-related fatigue: a preliminary study. Psychooncology. 2014;23(12):1431–1434. doi: 10.1002/pon.3553.
    1. Johnson JA, Garland SN, Carlson LE, Savard J, Simpson JSA, Ancoli-Israel S, Campbell TS. Bright light therapy improves cancer-related fatigue in cancer survivors: a randomized controlled trial. J Cancer Surviv. 2018;12(2):206-15.
    1. Küller R. The influence of light on circarhythms in humans. J Physiol Anthropol Appl Hum Sci. 2002;21(2):87–91. doi: 10.2114/jpa.21.87.
    1. Lucas RJ, Peirson SN, Berson DM, Brown TM, Cooper HM, Czeisler CA, Figueiro MG, Gamlin PD, Lockley SW, O’Hagan JB. Measuring and using light in the melanopsin age. Trends Neurosci. 2014;37(1):1–9. doi: 10.1016/j.tins.2013.10.004.
    1. Neikrug AB, Rissling M, Trofimenko V, Liu L, Natarajan L, Lawton S, Parker BA, Ancoli-Israel S. Bright light therapy protects women from circadian rhythm desynchronization during chemotherapy for breast cancer. Behav Sleep Med. 2012;10(3):202–216. doi: 10.1080/15402002.2011.634940.
    1. Wu LM, Amidi A, Valdimarsdottir H, Ancoli-Israel S, Liu L, Winkel G, Byrne EE, Sefair AV, Vega A, Bovbjerg K. The effect of systematic light exposure on sleep in a mixed group of fatigued cancer survivors. J Clin Sleep Med. 2018;14(01):31–39. doi: 10.5664/jcsm.6874.
    1. Figueiro MG, Rea MS. The effects of red and blue lights on circadian variations in cortisol, alpha amylase, and melatonin. Int J Endocrinol. 2010. vol. 2010, Article ID 829351, 9 pages. 10.1155/2010/829351.
    1. Bower JE, Ganz PA, Aziz N. Altered cortisol response to psychologic stress in breast cancer survivors with persistent fatigue. Psychosom Med. 2005;67(2):277–280. doi: 10.1097/01.psy.0000155666.55034.c6.
    1. Innominato PF, Mormont M-C, Rich TA, Waterhouse J, Lévi FA, Bjarnason GA. Circadian disruption, fatigue, and anorexia clustering in advanced cancer patients: implications for innovative therapeutic approaches. Integr Cancer Ther. 2009;8(4):361–370. doi: 10.1177/1534735409355293.
    1. Weinrib AZ, Sephton SE, DeGeest K, Penedo F, Bender D, Zimmerman B, Kirschbaum C, Sood AK, Lubaroff DM, Lutgendorf SK. Diurnal cortisol dysregulation, functional disability, and depression in women with ovarian cancer. Cancer. 2010;116(18):4410–4419. doi: 10.1002/cncr.25299.
    1. Anderson J, Glod C, Dai J, Cao Y, Lockley S. Lux vs. wavelength in light treatment of seasonal affective disorder. Acta Psychiatr Scand. 2009;120(3):203–212. doi: 10.1111/j.1600-0447.2009.01345.x.
    1. Schrepf A, Clevenger L, Christensen D, DeGeest K, Bender D, Ahmed A, Goodheart MJ, Dahmoush L, Penedo F, Lucci JA. Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: relationships with depression, fatigue, and disability. Brain Behav Immun. 2013;30:S126–S134. doi: 10.1016/j.bbi.2012.07.022.
    1. Bower JE, Lamkin DM. Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. Brain Behav Immun. 2013;30:S48–S57. doi: 10.1016/j.bbi.2012.06.011.
    1. Wang XS, Shi Q, Shah ND, Heijnen CJ, Cohen EN, Reuben JM, Orlowski RZ, Qazilbash MH, Johnson VE, Williams LA. Inflammatory markers and development of symptom burden in patients with multiple myeloma during autologous stem cell transplantation. Clin Cancer Res. 2014;20(5):1366–1374. doi: 10.1158/1078-0432.CCR-13-2442.
    1. Powell N, Tarr A, Sheridan JF. Psychosocial stress and inflammation in cancer. Brain Behav Immun. 2013;30:S41–S47. doi: 10.1016/j.bbi.2012.06.015.
    1. Lieverse R, Van Someren EJ, Nielen MM, Uitdehaag BM, Smit JH, Hoogendijk WJ. Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial. Arch Gen Psychiatry. 2011;68(1):61–70. doi: 10.1001/archgenpsychiatry.2010.183.
    1. Jansson-Fröjmark M. The work and social adjustment scale as a measure of dysfunction in chronic insomnia: reliability and validity. Behav Cogn Psychother. 2014;42(02):186–198. doi: 10.1017/S135246581200104X.
    1. Dekker N, Aleman B, Raemaekers J. The BETER survivorship care initiative for Hodgkin lymphoma; tailored survivorship care for late effects of treatment. Ned Tijdschr Geneeskd. 2015;159:A9269.
    1. Smets E, Garssen B, Bd B, De Haes J. The multidimensional fatigue inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. 1995;39(3):315–325. doi: 10.1016/0022-3999(94)00125-O.
    1. Oldenmenger WH, Pleun J, de Klerk C, van der Rijt CC. Cut points on 0–10 numeric rating scales for symptoms included in the Edmonton symptom assessment scale in cancer patients: a systematic review. J Pain Symptom Manag. 2013;45(6):1083–1093. doi: 10.1016/j.jpainsymman.2012.06.007.
    1. Mundt JC, Marks IM, Shear MK, Greist JM. The work and social adjustment scale: a simple measure of impairment in functioning. Br J Psychiatry. 2002;180(5):461–464. doi: 10.1192/bjp.180.5.461.
    1. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213. doi: 10.1016/0165-1781(89)90047-4.
    1. Ancoli-Israel S, Martin JL, Blackwell T, Buenaver L, Liu L, Meltzer LJ, Sadeh A, Spira AP, Taylor DJ. The SBSM guide to actigraphy monitoring: clinical and research applications. Behav Sleep Med. 2015;13(sup1):S4–S38. doi: 10.1080/15402002.2015.1046356.
    1. Radloff LS. The CES-D scale a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1(3):385–401. doi: 10.1177/014662167700100306.
    1. van der Bij AK, de Weerd S, Cikot RJ, Steegers EA, Braspenning J. Validation of the dutch short form of the state scale of the Spielberger state-trait anxiety inventory: considerations for usage in screening outcomes. Public Health Genomics. 2003;6(2):84–87. doi: 10.1159/000073003.
    1. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care. 1992;30(6):473-83.
    1. Stewart AL, Ware JE, Sherbourne CD, Wells KB. Psychological distress/well-being and cognitive functioning measures. In: Stewart AL, Ware JE, editors. Measuring functioning and well-being: the medical outcomes study approach. Edn. Durham: Duke University; 1992. pp. 102–142.
    1. Cleeland CS, Mendoza TR, Wang XS, Chou C, Harle MT, Morrissey M, Engstrom MC. Assessing symptom distress in cancer patients. Cancer. 2000;89(7):1634–1646. doi: 10.1002/1097-0142(20001001)89:7<1634::AID-CNCR29>;2-V.
    1. Dinges DF, Powell JW. Microcomputer analyses of performance on a portable, simple visual RT task during sustained operations. Behav Res Methods Instrum Comput. 1985;17(6):652–655. doi: 10.3758/BF03200977.
    1. Saan R, Deelman B. De 15-woordentest A en B (een voorlopige handleiding) Groningen: Afdeling Neuropsychologie, AZG; 1986.
    1. Wechsler D: Wechsler adult intelligence scale–fourth edition (WAIS–IV). In.; 2014.
    1. Custers JA, van den Berg SW, van Laarhoven HW, Bleiker EM, Gielissen MF, Prins JB. The cancer worry scale: detecting fear of recurrence in breast cancer survivors. Cancer Nurs. 2014;37(1):E44–E50. doi: 10.1097/NCC.0b013e3182813a17.
    1. Jacobsen P, Azzarello L, Hann D. Relation of catastrophizing to fatigue severity in women with breast cancer. Cancer Res Ther Control. 1999;8:155–164.
    1. de Vree B, Van der Werf S, Prins J, Bazelmans H, Vercoulen J, Servaes P, Vries Md: Meetinstrumenten bij chronische vermoeidheid. 2002.
    1. Stalder T, Kirschbaum C, Kudielka BM, Adam EK, Pruessner JC, Wüst S, Dockray S, Smyth N, Evans P, Hellhammer DH. Assessment of the cortisol awakening response: expert consensus guidelines. Psychoneuroendocrinology. 2016;63:414–432. doi: 10.1016/j.psyneuen.2015.10.010.
    1. Keijzer H, Smits MG, Duffy JF, Curfs LM. Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders. Sleep Med Rev. 2014;18(4):333–339. doi: 10.1016/j.smrv.2013.12.001.
    1. Voultsios A, Kennaway DJ, Dawson D. Salivary melatonin as a circadian phase marker: validation and comparison to plasma melatonin. J Biol Rhythm. 1997;12(5):457–466. doi: 10.1177/074873049701200507.
    1. Hoeck AD. Vitamin D3 deficiency results in dysfunctions of immunity with severe fatigue and depression in a variety of diseases. In Vivo. 2014;28(1):133–145.
    1. Biersack MG, Hajdukiewicz M, Uebelhack R, Franke L, Piazena H, Klaus P, Höhne-Zimmer V, Braun T, Buttgereit F, Burmester G-R. Sustained increase of 25-hydroxyvitamin D levels in healthy young women during wintertime after three suberythemal UV irradiations—the MUVY pilot study. PLoS One. 2016;11(7):e0159040. doi: 10.1371/journal.pone.0159040.
    1. Nowak A, Boesch L, Andres E, Battegay E, Hornemann T, Schmid C, Bischoff-Ferrari HA, Suter PM, Krayenbuehl P-A. Effect of vitamin D3 on self-perceived fatigue: a double-blind randomized placebo-controlled trial. Medicine. 2016;95(52):e5353.
    1. Schubert C, Hong S, Natarajan L, Mills PJ, Dimsdale JE. The association between fatigue and inflammatory marker levels in cancer patients: a quantitative review. Brain Behav Immun. 2007;21(4):413–427. doi: 10.1016/j.bbi.2006.11.004.
    1. Faul F, Erdfelder E, Lang A-G, Buchner A. G* power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–191. doi: 10.3758/BF03193146.
    1. Cohen J. Statistical power analysis for the behavioral sciences. Hilsdale: Lawrence Earlbaum Associates; 1988. p. 2.
    1. Diggle PJ, Heagerty PJ, Liang K-Y, Zeger SL. Analysis of longitudinal data. 2. New York: Oxford University Press; 2002.
    1. Son H, Friedmann E, Thomas SA. Application of pattern mixture models to address missing data in longitudinal data analysis using SPSS. Nurs Res. 2012;61(3):195–203. doi: 10.1097/NNR.0b013e3182541d8c.
    1. Ghisletta P, Spini D. An introduction to generalized estimating equations and an application to assess selectivity effects in a longitudinal study on very old individuals. J Educ Behav Stat. 2004;29(4):421–437. doi: 10.3102/10769986029004421.
    1. Liu I, Agresti A. The analysis of ordered categorical data: an overview and a survey of recent developments. Test. 2005;14(1):1–73. doi: 10.1007/BF02595397.
    1. Cella M, Sharpe M, Chalder T. Measuring disability in patients with chronic fatigue syndrome: reliability and validity of the work and social adjustment scale. J Psychosom Res. 2011;71(3):124–128. doi: 10.1016/j.jpsychores.2011.02.009.
    1. Vodermaier A, Linden W, Siu C. Screening for emotional distress in cancer patients: a systematic review of assessment instruments. J Natl Cancer Inst. 2009;101(21):1464–1488. doi: 10.1093/jnci/djp336.
    1. Aaronson NK, Muller M, Cohen PD, Essink-Bot M-L, Fekkes M, Sanderman R, Sprangers MA, te Velde A, Verrips E. Translation, validation, and norming of the Dutch language version of the SF-36 health survey in community and chronic disease populations. J Clin Epidemiol. 1998;51(11):1055–1068. doi: 10.1016/S0895-4356(98)00097-3.
    1. Yarlas A, White M, Bjorner J. The development and validation of a revised version of the medical outcomes study cognitive functioning scale (Mos-cog-R) Value Health. 2013;16(3):A33–A34. doi: 10.1016/j.jval.2013.03.194.
    1. Jacobsen PB, Andrykowski MA, Thors CL. Relationship of catastrophizing to fatigue among women receiving treatment for breast cancer. J Consult Clin Psychol. 2004;72(2):355. doi: 10.1037/0022-006X.72.2.355.
    1. 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(9259):841–847. doi: 10.1016/S0140-6736(00)04198-2.

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