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Published in: Trials 1/2020

01-12-2020 | Mood Disorders | Study protocol

Protocol for the Optimune trial: a randomized controlled trial evaluating a novel Internet intervention for breast cancer survivors

Authors: Franziska Holtdirk, Anja Mehnert, Mario Weiss, Björn Meyer, Carsten Watzl

Published in: Trials | Issue 1/2020

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Abstract

Introduction

Depression and fatigue are common in breast cancer survivors, and their presence is associated with personal suffering and worse prognosis. While many women receive short-term psychological support in the acute treatment phase, this is rarely available in subsequent phases. Internet interventions for breast cancer survivors could provide additional psychological support, as they are easily accessible and may be effective. However, no trial has yet examined the effectiveness of an Internet intervention that provides cognitive behavioural therapy techniques plus lifestyle advice for this population. This trial aims to test whether Optimune, a novel Internet intervention we developed for that purpose, leads to improvements in quality of life and relevant lifestyle habits over the course of 3 to 6 months.

Methods

This randomized controlled trial (RCT) will include 360 female breast cancer survivors who have completed the active tumour eradication phase. Participants will be recruited from various settings, including web-based advertisements and Internet forums in German-speaking countries. The main inclusion criteria are a breast cancer diagnosis less than 5 years ago and completion of acute treatment at least 1 month ago, as verified by discharge letter from an oncology treatment centre. Participants will be randomly assigned to either (1) a control group, in which they receive care as usual (CAU) and are given access to Optimune after a delay of 3 months (CAU/wait list control), or (2) a treatment group that may also use CAU and will receive 12-month access to Optimune immediately after randomization. The three primary endpoints are quality of life, physical activity and diet quality, assessed with the World Health Organization Quality of Life Questionnaire, the International Physical Activity Questionnaire and the Food Quality Questionnaire, at 3 months post-baseline; secondary outcomes include cancer-related fatigue, emotional stress, depression, anxiety, fear of progression, insomnia, usefulness of the programme and negative treatment effects. Online assessments are conducted at baseline (T0), 3 months (T1) and 6 months (T2).

Discussion

Results of this RCT are expected to extend the body of knowledge with regard to the effectiveness of CBT-based Internet interventions for female breast cancer survivors.

Trial registration

ClinicalTrials.gov, NCT03643640. Registered on 23 August 2018.
Appendix
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Literature
1.
2.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRefPubMed
3.
Kreienberg R, Albert U, Follmann M, Kopp I, Kühn T, Wöckel A. Interdisziplinäre S3-Leitlinie für die Diagnostik, Therapie und Nachsorge des Mammakarzinoms. Senologie - Zeitschrift für Mammadiagnostik und -therapie. 2013;10:164–92.CrossRef
4.
Abrahams HJG, Gielissen MFM, Schmits IC, Verhagen CAHHVM, Rovers MM, Knoop H. Risk factors, prevalence, and course of severe fatigue after breast cancer treatment: a meta-analysis involving 12 327 breast cancer survivors. Ann Oncol. 2016;27:965–74.PubMedCrossRef
5.
Bower JE, Ganz PA, Desmond KA, Bernaards C, Rowland JH, Meyerowitz BE, et al. Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer. 2006;106:751–8.PubMedCrossRef
6.
Maass SWMC, Roorda C, Berendsen AJ, Verhaak PFM, de Bock GH. The prevalence of long-term symptoms of depression and anxiety after breast cancer treatment: a systematic review. Maturitas. 2015;82:100–8.PubMedCrossRef
7.
Von Ah D, Kang D-H. Correlates of mood disturbance in women with breast cancer: patterns over time. J Adv Nurs. 2008;61:676–89.CrossRef
8.
Bower JE, Ganz PA, Aziz N, Fahey JL. Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med. 2002;64:604–11.PubMedCrossRef
9.
Collado-Hidalgo A, Bower JE, Ganz PA, Cole SW, Irwin MR. Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res. 2006;12:2759–66.PubMedCrossRef
10.
Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH, et al. Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol. 2009;27:3437–44.PubMedPubMedCentralCrossRef
11.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67:446–57.PubMedCrossRef
12.
Sanjida S, Janda M, Kissane D, Shaw J, Pearson S-A, DiSipio T, et al. A systematic review and meta-analysis of prescribing practices of antidepressants in cancer patients. Psychooncology. 2016;25:1002–16.PubMedCrossRef
13.
Juurlink D. Revisiting the drug interaction between tamoxifen and SSRI antidepressants. BMJ. 2016;354:i5309.PubMedCrossRef
14.
Hannestad J, DellaGioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology. 2011;36:2452–9.PubMedPubMedCentralCrossRef
15.
Köhler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, et al. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry. 2014;71:1381–91.PubMedCrossRef
16.
Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013;70:31–41.PubMedPubMedCentralCrossRef
17.
Del Grande da Silva G, Wiener CD, Barbosa LP, Gonçalves Araujo JM, Molina ML, San Martin P, et al. Pro-inflammatory cytokines and psychotherapy in depression: results from a randomized clinical trial. J Psychiatr Res. 2016;75:57–64.CrossRef
18.
Moreira FP, de Azevedo Cardoso T, Mondin TC, de Mattos Souza LD, Silva R, Jansen K, et al. The effect of proinflammatory cytokines in Cognitive Behavioral Therapy. J Neuroimmunol. 2015;285:143–6.PubMedCrossRef
19.
Walsh E, Eisenlohr-Moul T, Baer R. Brief mindfulness training reduces salivary IL-6 and TNF-α in young women with depressive symptomatology. J Consult Clin Psychol. 2016;84:887–97.PubMedPubMedCentralCrossRef
20.
Black DS, Slavich GM. Mindfulness meditation and the immune system: a systematic review of randomized controlled trials. Ann N Y Acad Sci. 2016;1373:13–24.PubMedPubMedCentralCrossRef
21.
Kiecolt-Glaser JK, Bennett JM, Andridge R, Peng J, Shapiro CL, Malarkey WB, et al. Yoga’s impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. J Clin Oncol. 2014;32:1040–9.PubMedPubMedCentralCrossRef
22.
Bower JE, Crosswell AD, Stanton AL, Crespi CM, Winston D, Arevalo J, et al. Mindfulness meditation for younger breast cancer survivors: a randomized controlled trial. Cancer. 2015;121:1231–40.PubMedCrossRef
23.
Carlson LE, Speca M, Patel KD, Goodey E. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients. Psychosomatic Medicine. 2003;65:571–81.PubMedCrossRef
24.
McGregor BA, Antoni MH. Psychological intervention and health outcomes among women treated for breast cancer: a review of stress pathways and biological mediators. Brain Behav Immun. 2009;23:159–66.PubMedCrossRef
25.
Cuijpers P. Psychotherapies for adult depression: recent developments. Current Opinion in Psychiatry. 2015;28:24–9.PubMedCrossRef
26.
Zimmermann-Schlegel V, Hartmann M, Sklenarova H, Herzog W, Haun MW. Accessibility, availability, and potential benefits of psycho-oncology services: the perspective of community-based physicians providing cancer survivorship care. Oncologist. 2017;22:719–27.PubMedPubMedCentralCrossRef
27.
Mohr DC, Ho J, Duffecy J, Baron KG, Lehman KA, Jin L, et al. Perceived barriers to psychological treatments and their relationship to depression. J Clin Psychol. 2010;66:394–409.PubMedPubMedCentral
28.
29.
Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, et al. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. CA Cancer J Clin. 2016;66:43–73.PubMedCrossRef
30.
National Institute for Clinical Excellence. Improving outcomes in breast cancer: manual update. London: National Institute for Clinical Excellence; 2002.
31.
Kazdin AE, Blase SL. Rebooting psychotherapy research and practice to reduce the burden of mental illness. Perspect Psychol Sci. 2011;6:21–37.PubMedCrossRef
32.
Beevers CG, Pearson R, Hoffman JS, Foulser AA, Shumake J, Meyer B. Effectiveness of an internet intervention (Deprexis) for depression in a United States adult sample: a parallel-group pragmatic randomized controlled trial. J Consult Clin Psychol. 2017;85:367–80.PubMedCrossRef
33.
Berger T, Hämmerli K, Gubser N, Andersson G, Caspar F. Internet-based treatment of depression: a randomized controlled trial comparing guided with unguided self-help. Cogn Behav Ther. 2011;40:251–66.PubMedCrossRef
34.
Berger T, Urech A, Krieger T, Stolz T, Schulz A, Vincent A, et al. Effects of a transdiagnostic unguided Internet intervention ('velibra’) for anxiety disorders in primary care: results of a randomized controlled trial. Psychol Med. 2017;47:67–80.PubMedCrossRef
35.
Fischer A, Schröder J, Vettorazzi E, Wolf OT, Pöttgen J, Lau S, et al. An online programme to reduce depression in patients with multiple sclerosis: a randomised controlled trial. Lancet Psychiatry. 2015;2:217–23.PubMedCrossRef
36.
Fuhr K, Fahse B, Hautzinger M, Gulewitsch M. Erste Erfahrungen zur Implementierbarkeit einer internet-basierten Selbsthilfe zur Überbrückung der Wartezeit auf eine ambulante Psychotherapie. PPmP - Psychother Psych Med Psych. 2018;68:234–41.CrossRef
37.
Gräfe V, Greiner W. Internet based treatment of depressive symptoms — a health economic evaluation of costs and benefits. Value Health. 2017;20:A714.CrossRef
38.
Klein JP, Berger T, Schröder J, Späth C, Meyer B, Caspar F, et al. Effects of a psychological internet intervention in the treatment of mild to moderate depressive symptoms: results of the evident study, a randomized controlled trial. Psychother Psychosom. 2016;85:218–28.PubMedCrossRef
39.
Meyer B, Berger T, Caspar F, Beevers CG, Andersson G, Weiss M. Effectiveness of a novel integrative online treatment for depression (Deprexis): randomized controlled trial. J Med Internet Res. 2009;11:e15.PubMedPubMedCentralCrossRef
40.
Meyer B, Bierbrodt J, Schröder J, Berger T, Beevers CG, Weiss M, et al. Effects of an Internet intervention (Deprexis) on severe depression symptoms: randomized controlled trial. Internet Interv. 2015;2:48–59.CrossRef
41.
Moritz S, Schilling L, Hauschildt M, Schröder J, Treszl A. A randomized controlled trial of internet-based therapy in depression. Behav Res Ther. 2012;50:513–21.PubMedCrossRef
42.
Schröder J, Brückner K, Fischer A, Lindenau M, Köther U, Vettorazzi E, et al. Efficacy of a psychological online intervention for depression in people with epilepsy: a randomized controlled trial. Epilepsia. 2014;55:2069–76.PubMedCrossRef
43.
Zwerenz R, Becker J, Knickenberg RJ, Siepmann M, Hagen K, Beutel ME. Online self-help as an add-on to inpatient psychotherapy: efficacy of a new blended treatment approach. Psychother Psychosom. 2017;86:341–50.PubMedCrossRef
44.
Twomey C, O’Reilly G, Meyer B. Effectiveness of an individually-tailored computerised CBT programme (Deprexis) for depression: a meta-analysis. Psychiatry Res. 2017;256:371–7.PubMedCrossRef
45.
Meyer B, Weiss M, Holtkamp M, Arnold S, Brückner K, Schröder J, et al. Effects of an epilepsy-specific Internet intervention (Emyna) on depression: results of the ENCODE randomized controlled trial. Epilepsia. 2019;60:656–68.PubMedCrossRef
46.
Pöttgen J, Moss-Morris R, Wendebourg J-M, Feddersen L, Lau S, Köpke S, et al. Randomised controlled trial of a self-guided online fatigue intervention in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018;89:970–6.PubMedCrossRef
47.
48.
Hotopf M. The pragmatic randomised controlled trial. Adv Psychiatr Treat. 2002;8:326–33.CrossRef
49.
Zwarenstein M, Treweek S. What kind of randomised trials do patients and clinicians need? Evid Based Med. 2009;14:101–3.PubMedCrossRef
50.
Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158:200–7.PubMedPubMedCentralCrossRef
51.
Eysenbach G, CONSORT-EHEALTH Group. CONSORT-EHEALTH: Improving and Standardizing Evaluation Reports of Web-based and Mobile Health Interventions. J Med Internet Res. 2011;13:e126.PubMedPubMedCentralCrossRef
52.
53.
54.
Yardley L, Morrison L, Bradbury K, Muller I. The person-based approach to intervention development: application to digital health-related behavior change interventions. J Med Internet Res. 2015;17:e30.PubMedPubMedCentralCrossRef
55.
56.
57.
Vickerstaff V, Ambler G, King M, Nazareth I, Omar RZ. Are multiple primary outcomes analysed appropriately in randomised controlled trials? A review. Contemp Clin Trials. 2015;45(Pt A):8–12.PubMedCrossRef
58.
The WHOQOL Group. Development of the World Health Organization WHOQOL-BREF Quality of Life Assessment. Psychol Med. 1998;28:551–8.CrossRef
59.
60.
Skevington SM, Lotfy M, O’Connell KA. The World Health Organization’s WHOQOL-BREF quality of life assessment: psychometric properties and results of the international field trial. A Report from the WHOQOL Group. Qual Life Res. 2004;13:299–310.CrossRefPubMed
61.
Lee PH, Macfarlane DJ, Lam T, Stewart SM. Validity of the International Physical Activity Questionnaire Short Form (IPAQ-SF): a systematic review. Int J Behav Nutr Phys Act. 2011;8:115.PubMedPubMedCentralCrossRef
62.
Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, et al. The rapid assessment of fatigue severity in cancer patients. Cancer. 1999;85:1186–96.PubMedCrossRef
63.
Radbruch L, Sabatowski R, Elsner F, Everts J, Mendoza T, Cleeland C. Validation of the German version of the Brief Fatigue Inventory. J Pain Symptom Manag. 2003;25:449–58.CrossRef
64.
Creamer M, Bell R, Failla S. Psychometric properties of the Impact of Event Scale-Revised. Behav Res Ther. 2003;41:1489–96.PubMedCrossRef
65.
Kroenke K, Spitzer RL. The PHQ-9: a new depression diagnostic and severity measure. Psychiatr Ann. 2002;32:509–15.CrossRef
66.
67.
Löwe B, Decker O, Müller S, Brähler E, Schellberg D, Herzog W, et al. Validation and standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population. Med Care. 2008;46:266–74.PubMedCrossRef
68.
Spitzer RL, Kroenke K, Williams JBW, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092–7.CrossRefPubMed
69.
Herschbach P, Berg P, Engst-Hastreiter U, Waadt S, Duran G, Henrich G. Entwicklung und Evaluation eines Therapieprogramms zur Bewältigung von Progredienzangst. Munich: Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie, Klinikum rechts der Isar, Technische Universität München; 2006.
70.
Herschbach P, Dankert A, Duran-Atzinger G, Waadt S, Engst-Hastreiter U, Keller M, et al. Diagnostik von Progredienzangst – Entwicklung eines Fragebogens zur Erfassung von Progredienzangst bei Patienten mit Krebserkrankungen, Diabetes mellitus und entzündlich-rheumatischen Erkrankungen in der Rehabilitation. Munich: Institut für Psychosomatische Medizin, medizinische Psychologie und Psychotherapie der TU-München; 2001.
71.
Morin CM, Belleville G, Bélanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011;34:601–8.PubMedPubMedCentralCrossRef
72.
Keiningham TL, Aksoy L, Cooil B, Andreassen TW, Williams L. A holistic examination of Net Promoter. J Database Mark Cust Strategy Manag. 2008;15:79–90.CrossRef
73.
74.
Ledesma D, Kumano H. Mindfulness-based stress reduction and cancer: a meta-analysis. Psycho-Oncology. 2009;18:571–9.PubMedCrossRef
75.
Musial F, Büssing A, Heusser P, Choi K-E, Ostermann T. Mindfulness-based stress reduction for integrative cancer care — a summary of evidence. Forschende Komplementärmedizin/Research in Complementary Medicine. 2011;18:192–202.PubMedCrossRef
76.
Tatrow K, Montgomery GH. Cognitive behavioral therapy techniques for distress and pain in breast cancer patients: a meta-analysis. J Behav Med. 2006;29:17–27.PubMedCrossRef
77.
Gupta S. Intention-to-treat concept: a review. Perspectives Clin Res. 2011;2:109.CrossRef
78.
79.
Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials — a practical guide with flowcharts. BMC Med Res Methodol. 2017;17:162.PubMedPubMedCentralCrossRef
80.
O’Connell NS, Dai L, Jiang Y, Speiser JL, Ward R, Wei W, et al. Methods for analysis of pre-post data in clinical research: a comparison of five common methods. J Biom Biostat. 2017;8:1–8.PubMedPubMedCentral
81.
EMEA. ICH E9 statistical principles for clinical trials. London: European Medicines Agency; 1998.
Metadata
Title
Protocol for the Optimune trial: a randomized controlled trial evaluating a novel Internet intervention for breast cancer survivors
Authors
Franziska Holtdirk
Anja Mehnert
Mario Weiss
Björn Meyer
Carsten Watzl
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-019-3987-y

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