A Feasibility Study in Chronically Fatigued Cancer Survivors

Study Overview
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Brief Summary
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Improved cancer survival has led to increased attention on long-term health and quality of life (QoL) among the survivors. Both the cancer diagnosis and intensive treatments increase the risk of late effects which may interfere with daily physical, psychological and social functioning, and thereby negatively affect their QoL. Well-documented late-effects among cancer survivors are second cancer, cardio-vascular disease, pain, hormone disturbances, mental distress and chronic fatigue (CF). CF is a subjective experience of substantial lack of energy, exhaustion and cognitive difficulties lasting for six months or longer. CF is one of the most common and distressing late effects after cancer, affecting 15-35 % of survivors, often for years beyond treatment. Despite the high prevalence and the huge negative consequences of CF on daily functioning and QoL and the economic and societal costs, effective treatment of CF and standardized follow-up care are currently lacking. CF is a complex condition best understood as a multifactorial phenomenon. Our and other research groups have examined various cohorts of cancer survivors in order to identify behavioral-, psychological-, and biological factors associated with CF, that can form the basis for targeted interventions. So far, few treatable biological factors have been identified, even though immune activation, flattened diurnal cortisol slopes and a blunted cortisol response to stress have been demonstrated in small studies among cancer survivors suffering from CF. On the other hand, several modifiable behavioral factors including emotional distress, physical inactivity, sleep disturbances and unhealthy diets are found to be associated with CF. So far, most of the interventions aiming to reduce fatigue during and shortly after cancer treatment have targeted only one of these factors at a time, with small to moderate effect sizes. No prior study has examined if CF in cancer survivors is better treated by a complex intervention targeting combinations of these factors, an approach which seems logical due to the complexity of the symptom. The Division of Cancer Medicine at Oslo University Hospital (OUH) presently offers limited rehabilitation programs, including patient education, physical exercise, cognitive behavioral program and nutrition counselling to cancer survivors with CF. However, these programs are not offered as an interdisciplinary intervention integrated in a standardized patient care pathway, and the effects of these interventions have not been assessed. Based on the investigators clinical experience and published studies on single-targeted interventions, the investigators hypothesize that a complex intervention including psycho-educational elements, physical exercise and nutrition counseling delivered as a standardized patient care pathway is well-founded and doable, and will improve fatigue, functioning and QoL in cancer survivors with CF. During the fall of 2021, the investigators will conduct a randomized controlled trial (RCT) with the overall objective to improve fatigue in lymphoma survivors with CF. To uncover strengths and weaknesses with the planned RCT, i.e. the inclusion procedures, the assessments and the complex intervention, the investigators are now conducting a small one-armed feasibility study before the RCT during spring 2021.

Official Title
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A Feasibility Study in Chronically Fatigued Cancer Survivors

Conditions
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Fatigue, Lymphoma

Intervention / Treatment
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* Other: A 12-week interdisciplinary complex intervention


Participation Criteria
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Eligibility Criteria
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Seven lymphoma survivors will be included, with the same inclusion criteria as in the planned RCT: Inclusion Criteria: Survivors of Hodgkin and aggressive non-Hodgkin lymphoma, diagnosed 2014 or 2019 (n=7) 18-65 years at diagnosis, and 19-67 years at participation. CF measured by Chalder FQ. Curatively treated, more than 2 years since last treatment. Participation approval from oncologist. Exclusion Criteria: Indolent non-Hodgkin lymphoma. Fatigue more than one year before the cancer diagnosis. Ongoing cancer treatment, relapse or second cancer, somatic/physical conditions (i.e. severe heart failure/disease, lung disease, use of wheelchair /crutches). Psychiatric disorders (i.e. severe depression, schizophrenia), substance abuse disorder. In addition, eight cancer survivors with various diagnosis, will be included from a waiting list for rehabilitation at the Cancer Rehabilitation Centre at Aker hospital.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 67 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interdisciplinary complex intervention<br>The intervention includes patient education, physical exercise, a group-based cognitive behavioral program and individual nutritional counseling | Other: A 12-week interdisciplinary complex intervention<br>* The intervention will last for 12 weeks and includes four components; patient education, physical exercise, cognitive behavioral program and nutritional counseling. The patient education will include an online 2-hours group-based patient-education sessions in week 1. The physical exercise program includes two weekly exercise sessions, one supervised by a physiotherapist and one unsupervised, including aerobic exercise, resistance exercise and psychometric physiotherapy. Half of the intervention group (N=7) will perform the supervised exercise session individually with a physiotherapist in the municipality, while the other half (n=8) will exercise in online groups lead by physiotherapists. The cognitive behavioral program will begin in week 3 and include six group-based online sessions every week lead by a clinical psychologist. The nutritional counseling will include three individual digital nutrition counselling sessions in week 2, 6 and 10 by a clinical dietitian.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | Assessed by the number who consent to participate | The week before the intervention period (week 0) | 
| Inclusion rate | Assessed by the number of consenting participants who are included (i.e. have chronic fatigue according to the Fatigue Questionnaire, and are cleared for participation by oncologist after the medical screening). | The week before the intervention period (week 0) | 
| Completion rate | Assessed by the number of consenting participants consenting patients who complete any measurement at the final assessment | The week before the intervention period (week 0) | 
| Strengths and weaknesses with the inclusion procedure: participants | Assessed by structured conversations with the participants | Week 4 | 
| Strengths and weaknesses with the inclusion procedure: study personnel | Assessed by structured conversations with the study personnel | Week 4 | 
| Feasibility of the patient education session: participants | Strengths, weaknesses, and usefulness of the contents in the education session will be assessed by structured conversations with the participants after the patient education session. | Week 4 | 
| Feasibility of the patient education session: presenters | Strengths, weaknesses, and usefulness of the contents in the education session will be assessed by structured conversations with the presenters after the patient education session. | Week 4 | 
| Feasibility of the exercise program part one (week 1-3): participants | Strengths and weaknesses with the exercise program will be evaluated through structured conversations with the participants | Week 4 | 
| Feasibility of the exercise program part one (week 1-3): physiotherapists | Strengths and weaknesses with the exercise program will be evaluated through structured conversations with the physiotherapists | Week 4 | 
| Feasibility of the exercise program part two (week 4-7): participants | Strengths and weaknesses with the exercise program will be evaluated through structured conversations with the participants | Week 8 | 
| Feasibility of the exercise program part two (week 4-7): physiotherapists | Strengths and weaknesses with the exercise program will be evaluated through structured conversations with the physiotherapists | Week 8 | 
| Compliance to the cognitive behavioral therapy groups sessions | Participation to the cognitive behavioral therapy groups sessions will be registered by the study coordinators/psychologists.. | Week 8 | 
| Feasibility of the cognitive behavioral therapy groups sessions: participants | Strengths, weaknesses, and usefulness of the groups sessions will be assessed by structured conversations with the participants after the last group session | Week 8 | 
| Feasibility of the cognitive behavioral therapy groups sessions: psychologists | Strengths, weaknesses, and usefulness of the groups sessions will be assessed by structured conversations with the psychologists after the last group session | Week 8 | 
| Compliance to the nutrition counseling | Participation rate of the individual nutrition counseling sessions will be registered by the clinical dietitian. | Week 11 | 
| Feasibility of the nutrition counseling: participants | Strengths, weaknesses, and usefulness of the contents in the sessions will be assessed by structured conversations with the participants after the last counseling session. | Week 11 | 
| Feasibility of the nutrition counseling: clinical dietitian | Strengths, weaknesses, and usefulness of the contents in the sessions will be assessed by structured conversations with the clinical dietitian after the last counseling session. | Week 11 | 
| Compliance to the exercise program: attendance | Registered by the physiotherapists in an exercise log | Week 13 | 
| Compliance to the exercise program: intensity during the aerobic exercise intervals | Registered by pulse sensors | Week 13 | 
| Compliance to the exercise program: implementation of the strength training exercises | Registered by the physiotherapists in an exercise log | Week 13 | 
| Feasibility of the exercise program part three (week 8-12): participants | Strengths and weaknesses with the exercise program will be evaluated through structured conversations with the participants | Week 13 | 
| Feasibility of the exercise program part three (week 8-12): physiotherapists | Strengths and weaknesses with the exercise program will be evaluated through structured conversations with the physiotherapists | Week 13 | 
| Feasibility of the questionnaires | Strengths and weaknesses with the questionnaire will be evaluated through structured conversations with the participants. | Week 13 | 
| Feasibility of the physical tests: participants | Strengths and weaknesses with the tests will be evaluated through structured conversations with the participants. | Week 13 | 
| Feasibility of the physical tests: physiotherapists | Strengths and weaknesses with the tests will be evaluated through structured conversations with the physiotherapists conducting the tests. | Week 13 | 
| Compliance to the physical tests | Assessed by the completion rate of the physical tests (i.e. the number of participants who conduct the tests as planned). | Week 13 | 
| Completeness of the questionnaires | Assessed by the completion rate of the questionnaire (i.e. proportion of missing). | Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in level of fatigue | Measured by Chalder Fatigue Questionnaire. Total score range from 0 to 33, with increasing score implying more fatigue. | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in level of fatigue | Measured by Chalder Fatigue Questionnaire. Total score range from 0 to 33, with increasing score implying more fatigue. | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in level of fatigue | Measured by Chalder Fatigue Questionnaire. Total score range from 0 to 33, with increasing score implying more fatigue. | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in daily functioning and global quality of life | Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30). Scores range fro 0 to 100, a higher score represents a higher (better) level of functioning or a higher (worse) level of symptoms. | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in daily functioning and global quality of life | Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30). Scores range fro 0 to 100, a higher score represents a higher (better) level of functioning or a higher (worse) level of symptoms. | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in daily functioning and global quality of life | Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30). Scores range fro 0 to 100, a higher score represents a higher (better) level of functioning or a higher (worse) level of symptoms. | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in subjective well-being | Measured by the Satisfaction with Life Scale. Total score range from 5 to 35, with increasing score implying higher subjective well-being. | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in vitality | Measured by the Subjective Vitality Scale. The total score ranges from 6 to 36 with a higher score indicating a better condition | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in general health | Measured by European Quality of Life Five-dimension Scale Questionnaire (EQ-5D). Total score range from 5 (worst health) to 25 (best health). | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in work ability | Measured by Work Ability Index. Total score range from 7 to 49 points, with higher score indicating better work ability. | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in work ability | Measured by Work Ability Index. Total score range from 7 to 49 points, with higher score indicating better work ability. | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in work ability | Measured by Work Ability Index. Total score range from 7 to 49 points, with higher score indicating better work ability. | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in anxiety symptoms | Measured by the General Anxiety Disorder 7-items. Total score range from 0 to 21 with increasing score implying higher level of anxiety. | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in anxiety symptoms | Measured by the General Anxiety Disorder 7-items. Total score range from 0 to 21 with increasing score implying higher level of anxiety. | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in anxiety symptoms | Measured by the General Anxiety Disorder 7-items. Total score range from 0 to 21 with increasing score implying higher level of anxiety. | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in depressive symptoms | Measured by the Patient Health Questionnaire-9. Total score from 0 to 27, increasing score implying higher depressive symptoms. | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in depressive symptoms | Measured by the Patient Health Questionnaire-9. Total score from 0 to 27, increasing score implying higher depressive symptoms. | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in depressive symptoms | Measured by the Patient Health Questionnaire-9. Total score from 0 to 27, increasing score implying higher depressive symptoms. | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in level of physical activity | Measured by the Godin Leisure Time Exercise Questionnaire | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in level of physical activity | Measured by the Godin Leisure Time Exercise Questionnaire | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in level of physical activity | Measured by the Godin Leisure Time Exercise Questionnaire | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in exercise mastery | Assessed by the Perceived Competence Scale. The scale consists of 4 items (statements). On each item, participants are asked to rate how true a statement is using a 7-point scale.Total score range from 4 to 28, with increasing score reflecting higher exercise mastery. | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in exercise mastery | Assessed by the Perceived Competence Scale. The scale consists of 4 items (statements). On each item, participants are asked to rate how true a statement is using a 7-point scale.Total score range from 4 to 28, with increasing score reflecting higher exercise mastery. | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in exercise mastery | Assessed by the Perceived Competence Scale. The scale consists of 4 items (statements). On each item, participants are asked to rate how true a statement is using a 7-point scale.Total score range from 4 to 28, with increasing score reflecting higher exercise mastery. | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in dietary intake of the participants | Measured by a digital food frequency questionnaire (DIGIKOST-FFQ) | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in meal pattern | Measured by the Meal Pattern Questionnaire | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in body mass index | Calculated by measuring weight and height | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in body mass index | Calculated by measuring weight and height | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in body mass index | Calculated by measuring weight and height | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in sleep problems | Measured by questions from the Trøndelag Health Survey | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in sleep problems | Measured by questions from the Trøndelag Health Survey | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in sleep problems | Measured by questions from the Trøndelag Health Survey | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in cardiorespiratory fitness | Assessed by a submaximal and indirect treadmill test (modified Balke protocol) | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in cardiorespiratory fitness | Assessed by a submaximal and indirect treadmill test (modified Balke protocol) | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in cardiorespiratory fitness | Assessed by a submaximal and indirect treadmill test (modified Balke protocol) | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in lower body muscle strength | Assessed by 30 second sit-to-stand test | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in lower body muscle strength | Assessed by 30 second sit-to-stand test | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in lower body muscle strength | Assessed by 30 second sit-to-stand test | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in upper body muscle strength | Assessed by maximum repetitions of push-ups with various starting positions | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in upper body muscle strength | Assessed by maximum repetitions of push-ups with various starting positions | Change from baseline (week 0) to 4 months follow-up (week 29) | 
| Change in upper body muscle strength | Assessed by maximum repetitions of push-ups with various starting positions | Change from baseline (week 0) to 7 months follow-up (week 42) | 
| Change in quality of life among relatives | Assessed by the Research and Development 36-item Short Form Survey (RAND SF-36).The eight scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better quality of life. | Change from baseline (week 0) and to post-intervention (week 13) | 
| Change in global health status among relatives | The global health status / quality of life scale from the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30). Scores range from 0 to 100, a higher score represents a higher (better) level of functioning or a higher (worse) level of symptoms. | Change from baseline (week 0) and to post-intervention (week 13) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, chronic fatigue, lymphoma, cancer survivors, nutrition, cognitive therapy, patient education