A Complex Intervention for Chronically Fatigued Lymphoma Survivors

Study Overview
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Brief Summary
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The present study is a randomized controlled trial (RCT) with an overall objective to examine the effect of an interdisciplinary complex intervention on the level of fatigue in lymphoma survivors with chronic fatigue. Secondary aims are to examine the effects of the intervention on daily functioning, work ability, physical fitness, QoL and cortisol secretion among the survivors, on QoL of their relatives and on the societal costs.The intervention will last for 12+12 weeks and include four components; patient education, supervised physical exercise, cognitive behavioral program and nutritional counselling. Outcomes will be assessed at baseline,post-intervention (12 weeks after baseline) and at 3-month and 6-month follow-up after completed intervention.

Detailed Description
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Chronic fatigue (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. Today, there is no curative treatment of CF. However, 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 project is a two-armed RCT in which chronically fatigued lymphoma survivors are randomized to an interdisciplinary complex intervention or to usual care. Eligible participants will receive written information about the study by mail. Survivors who perceive themselves as having physical and mental fatigue, and who are willing to participate, will be asked to fill out and return the Chalder Fatigue Questionnaire (FQ) to the study coordinator. Those who have chronic fatigue as measured by the FQ will be invited to a medical screening by an oncologist in the project group, for evaluation of inclusion. The interdisciplinary complex intervention will last for 12 + 12 weeks and include four components; patient education, physical exercise (and follow-up), cognitive behavioral program and nutritional counselling, organized in a systematic way, i.e. a standardized patient care pathway. All outcomes will be assessed in all participants at four points; pre-intervention (baseline) (T0), post-intervention (12 weeks after baseline) (T1) and at 3-month (T2) and 6-month (T3) after T1.

Official Title
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A Complex Intervention for a Complex Symptom - a Randomized Controlled Trial in Chronically Fatigued Lymphoma Survivors

Conditions
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Chronic Fatigue Syndrome

Intervention / Treatment
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* Other: Interdisciplinary complex intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Survivors of Hodgkin and aggressive non-Hodgkin lymphoma Not indolent non-Hodgkin lymphoma Not CNS lymphoma at diagnosis Not second cancer Not ongoing cancer treatment Chronic fatigue measured by Chalder Fatigue Questionnaire Diagnosed 2010-2020 Received treatment with curative intent 18 - 70 years old at inclusion > 2 years since last treatment Able to understand the Norwegian language Participation approval from oncologist in the project group Exclusion Criteria: Persisting fatigue > 1 year before the cancer diagnosis Somatic/physical conditions (i.e. severe heart failure/disease, lung disease, use of wheelchair /crutches) Psychiatric or mental disorders (i.e. dementia, severe depression, schizophrenia) Use of stimulants for ADHD Substance abuse disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interdisciplinary complex intervention<br> | Other: Interdisciplinary complex intervention<br>* The interdisciplinary complex intervention lasts 12 weeks and includes the 4 following components; Patient-education: a 2-hours group-based digital session, including information about fatigue, training theory, psychological strategies and nutrition, all in relation to chronic fatigue (CF). Physical exercise program: two weekly sessions with aerobic exercise and resistance training. The participants are instructed to do the same program in the unsupervised sessions as in the supervised sessions. After the first 12 weeks exercise period, the participant and the physiotherapist makes an individually tailored plan for exercise and follow-up the next 12 weeks. Cognitive behavioral program: 6 group-based online sessions lead by two psychologists, based on elements from cognitive behavioral therapy to reduce and/or manage CF. Each session lasts for 135 minutes. Nutritional counselling: 3 individual sessions by a clinical dietitian. Each session lasts for 30-60 minutes.<br>|
| No Intervention: Usual care<br>Six months after the intervention period (T3), the participants randomized to usual care will be offered a modified version of the intervention in line with their personally expressed needs. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of the level of fatigue (physical-, mental- and total fatigue) assessed by the Chalder Fatigue Questionnaire | The Fatigue Questionnaire consists of 11 questions, distributed on a physical fatigue scale (7 items) and mental fatigue scale (4 items) Each item is scored from 0 to 3. This provides a physical fatigue score from 0 to 21, mental fatigue score from 0 to 12, and total score from 0 to 33. Higher score implies more fatigue. | From baseline (T0) to 12 weeks (T1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the level of fatigue assessed by Chalder Fatigue Questionnaire | The Fatigue Questionnaire consists of 11 questions, distributed on a physical fatigue scale (7 items) and mental fatigue scale (4 items) Each item is scored from 0 to 3, providing a total score from 0 to 33. Higher score implies more fatigue. | From baseline (T0) to 24 weeks (T2) | 
| Change of the level of fatigue assessed by Chalder Fatigue Questionnaire | The Fatigue Questionnaire consists of 11 questions, distributed on a physical fatigue scale (7 items) and mental fatigue scale (4 items) Each item is scored from 0 to 3, providing a total score from 0 to 33. Higher score implies more fatigue. | From baseline (T0) to 36 weeks (T3) | 
| Change in daily functioning assessed by European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). | The questionnaire includes five functioning scales (physical, role, cognitive, emotional and social).All of the scales range in score from 0 to 100. A high score for a functional scale represents a high / healthy level of functioning. | From baseline (T0) to 12 weeks (T1) | 
| Change in daily functioning assessed by European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). | The questionnaire includes five functioning scales (physical, role, cognitive, emotional and social).All of the scales range in score from 0 to 100. A high score for a functional scale represents a high / healthy level of functioning. | From baseline (T0) to 24 weeks (T2) | 
| Change in daily functioning assessed by European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). | The questionnaire includes five functioning scales (physical, role, cognitive, emotional and social).All of the scales range in score from 0 to 100. A high score for a functional scale represents a high / healthy level of functioning. | From baseline (T0) to 36 weeks (T3) | 
| Change in global quality of life assessed by European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). | The questionnaire includes a global health status / quality of life (QoL) scale, which range in score from 0 to 100. A high score for the global health status / QoL represents a high QoL. | From baseline (T0) to 12 weeks (T1) | 
| Change in global quality of life assessed by European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). | The questionnaire includes a global health status / quality of life (QoL) scale, which range in score from 0 to 100. A high score for the global health status / QoL represents a high QoL. | From baseline (T0) to 36 weeks (T3) | 
| Change in global quality of life assessed by European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). | The questionnaire includes a global health status / quality of life (QoL) scale, which range in score from 0 to 100. A high score for the global health status / QoL represents a high QoL. | From baseline (T0) to 24 weeks (T2) | 
| Change in work ability assessed by the Work Ability Index scale | Current work ability is rated compared with the lifetime best on a scale from 0 to 10. Higher score implies higher work ability. | From baseline (T0) to 12 weeks (T1) | 
| Change in work ability assessed by the Work Ability Index scale | Current work ability is rated compared with the lifetime best on a scale from 0 to 10. Higher score implies higher work ability. | From baseline (T0) to 24 weeks (T2) | 
| Change in work ability assessed by the Work Ability Index scale | Current work ability is rated compared with the lifetime best on a scale from 0 to 10. Higher score implies higher work ability. | From baseline (T0) to 36 weeks (T3) | 
| Change in work ability assessed by the Work Ability Index: physical demands of the job | Assessed by rating work ability in relation to the physical demands of the job, by the following response alternatives: very good, rather good, moderate, rather poor or very poor | From baseline (T0) to 12 weeks (T1) | 
| Change in work ability assessed by the Work Ability Index: physical demands of the job | Assessed by rating work ability in relation to the physical demands of the job, by the following response alternatives: very good, rather good, moderate, rather poor or very poor | From baseline (T0) to 24 weeks (T2) | 
| Changes in work ability assessed by the Work Ability Index: physical demands of the job | Assessed by rating work ability in relation to the physical demands of the job, by the following response alternatives: very good, rather good, moderate, rather poor or very poor | From baseline (T0) to 36 weeks (T3) | 
| Changes in work ability assessed by the Work Ability Index: psychological demands of the job | Assessed by rating work ability in relation to the psychological demands of the job, by the following response alternatives: very good, rather good, moderate, rather poor or very poor | From baseline (T0) to 12 weeks (T1) | 
| Change in work ability assessed by the Work Ability Index: psychological demands of the job | Assessed by rating work ability in relation to the psychological demands of the job, by the following response alternatives: very good, rather good, moderate, rather poor or very poor | From baseline (T0) to 24 weeks (T2) | 
| Change in work ability assessed by the Work Ability Index: psychological demands of the job | Assessed by rating work ability in relation to the psychological demands of the job, by the following response alternatives: very good, rather good, moderate, rather poor or very poor | From baseline (T0) to 36 weeks (T3) | 
| Change in cardiorespiratory fitness assessed by cardio-pulmonary exercise testing (CPET) | Peak oxygen uptake (VO2peak) is measured | From baseline (T0) to 12 weeks (T1) | 
| Change in cardiorespiratory fitness assessed by cardio-pulmonary exercise testing (CPET) | Peak oxygen uptake (VO2peak) is measured | From baseline (T0) to 24 weeks (T2) | 
| Change in cardiorespiratory fitness assessed by cardio-pulmonary exercise testing (CPET) | Peak oxygen uptake (VO2peak) is measured | From baseline (T0) to 36 weeks (T3) | 
| Change in cardiorespiratory fitness assessed by a treadmill test | In cases where participants do not have the opportunity to travel for physical fitness tests, cardiorespiratory fitness will be assessed by an indirect treadmill test (modified Balke protocol) at their local physiotherapist. Time to exhaustion will be used as an indicator of cardiorespiratory fitness. | From baseline (T0) to 12 weeks (T1) | 
| Change in cardiorespiratory fitness assessed by a treadmill test | In cases where participants do not have the opportunity to travel for physical fitness tests, cardiorespiratory fitness will be assessed by an indirect treadmill test (modified Balke protocol) at their local physiotherapist. Time to exhaustion will be used as an indicator of cardiorespiratory fitness. | From baseline (T0) to 24 weeks (T2) | 
| Change in cardiorespiratory fitness assessed by a treadmill test | In cases where participants do not have the opportunity to travel for physical fitness tests, cardiorespiratory fitness will be assessed by an indirect treadmill test (modified Balke protocol) at their local physiotherapist. Time to exhaustion will be used as an indicator of cardiorespiratory fitness. | From baseline (T0) to 36 weeks (T3) | 
| Change in lower body muscle strength assessed by leg press | The one-repetition maximum (1RM) test (the maximal workload that can be lifted once)) in leg press. | From baseline (T0) to 12 weeks (T1) | 
| Change in lower body muscle strength assessed by leg press | The one-repetition maximum (1RM) test (the maximal workload that can be lifted once)) in leg press. | From baseline (T0) to 24 weeks (T2) | 
| Change in lower body muscle strength assessed by leg press | The one-repetition maximum (1RM) test (the maximal workload that can be lifted once)) in leg press. | From baseline (T0) to 36 weeks (T3) | 
| Change in upper body muscle strength assessed by push-ups | The maximum number of push-ups that can be performed in one set | From baseline (T0) to 12 weeks (T1) | 
| Change in upper body muscle strength assessed by push-ups | The maximum number of push-ups that can be performed in one set | From baseline (T0) to 24 weeks (T2) | 
| Change in upper body muscle strength assessed by push-ups | The maximum number of push-ups that can be performed in one set | From baseline (T0) to 36 weeks (T3) | 
| Change in level of depressive symptoms assessed by the Patient Health Questionnaire-9 | Each of the 9 items is scored from 0-3, providing a total score from 0 to 27. A higher score implies higher level of depressive symptoms. | From baseline (T0) to 12 weeks (T1) | 
| Change in level of depressive symptoms assessed by the Patient Health Questionnaire-9 | Each of the 9 items is scored from 0-3, providing a total score from 0 to 27. A higher score implies higher level of depressive symptoms. | From baseline (T0) to 24 weeks (T2) | 
| Change in level of depressive symptoms assessed by the Patient Health Questionnaire-9 | Each of the 9 items is scored from 0-3, providing a total score from 0 to 27. A higher score implies higher level of depressive symptoms. | From baseline (T0) to 36 weeks (T3) | 
| Change in level of anxiety symptoms assessed by the General Anxiety Disorder 7-items (GAD7). | Each of the 7 items is scored from 0-3, providing a total score from 0-21. A higher score implies higher level of anxiety symptoms. | From baseline (T0) to 12 weeks (T1) | 
| Change in level of anxiety symptoms assessed by the General Anxiety Disorder 7-items (GAD7). | Each item is scored from 0-3, providing a total score from 0-21. A higher score implies higher level of anxiety symptoms. | From baseline (T0) to 24 weeks (T2) | 
| Change in level of anxiety symptoms assessed by the General Anxiety Disorder 7-items (GAD7). | Each of the 7 items is scored from 0-3, providing a total score from 0-21. A higher score implies higher level of anxiety symptoms. | From baseline (T0) to 36 weeks (T3) | 
| Changes in sense of exercise competence assessed by the Perceived Competence Scale. | The scale consists of 4 items, each scored from 1 (totally disagree) to 7 (totally agree). A sum score from 0 to 7 is calculated based on the mean score of the items, with increasing score implying higher exercise competence. | From baseline (T0) to 12 weeks (T1) | 
| Change in sense of exercise competence assessed by the Perceived Competence Scale. | The scale consists of 4 items, each scored from 1 (totally disagree) to 7 (totally agree). A sum score from 0 to 7 is calculated based on the mean score of the items, with increasing score implying higher exercise competence. | From baseline (T0) to 24 weeks (T2) | 
| Change in sense of exercise competence assessed by the Perceived Competence Scale. | The scale consists of 4 items, each scored from 1 (totally disagree) to 7 (totally agree). A sum score from 0 to 7 is calculated based on the mean score of the items, with increasing score implying higher exercise competence. | From baseline (T0) to 36 weeks (T3) | 
| Change in satisfaction with life assessed by the Satisfaction With Life Scale. | The scale consists of 5 items, each scored from 1 (totally disagree) to 7 (totally agree). A sum score from 5 to 35 is calculated, with increasing score implying higher satisfaction with life. | From baseline (T0) to 12 weeks (T1) | 
| Changes in satisfaction with life assessed by the Satisfaction With Life Scale. | The scale consists of 5 items, each scored from 1 (totally disagree) to 7 (totally agree). A sum score from 5 to 35 is calculated, with increasing score implying higher satisfaction with life. | From baseline (T0) to 24 weeks (T2) | 
| Change in satisfaction with life assessed by the Satisfaction With Life Scale. | The scale consists of 5 items, each scored from 1 (totally disagree) to 7 (totally agree). A sum score from 5 to 35 is calculated, with increasing score implying higher satisfaction with life. | From baseline (T0) to 36 weeks (T3) | 
| Change in sense of vitality assessed by the Subjective Vitality Scale | The scale consists of 5 items, each scored from 1 (totally disagree) to 7 (totally agree). A sum score from 5 to 35 is calculated, with increasing score implying higher sense of vitality. | From baseline (T0) to 12 weeks (T1) | 
| Change in sense of vitality assessed by the Subjective Vitality Scale | The scale consists of 5 items, each scored from 1 (totally disagree) to 7 (totally agree). A sum score from 5 to 35 is calculated, with increasing score implying higher sense of vitality. | From baseline (T0) to 24 weeks (T2) | 
| Changes in sense of vitality assessed by the Subjective Vitality Scale | The scale consists of 5 items, each scored from 1 (totally disagree) to 7 (totally agree). A sum score from 5 to 35 is calculated, with increasing score implying higher sense of vitality. | From baseline (T0) to 36 weeks (T3) | 
| Change in adherence to the Norwegian food-based dietary guidelines assessed by DIGIKOST-FFQ | DIGIKOST-FFQ is a food frequency questionnaire aiming to benchmark against the Norwegian food-based dietary guidelines. | From baseline (T0) to 12 weeks (T1) | 
| Changes in adherence to the Norwegian food-based dietary guidelines assessed by DIGIKOST-FFQ | DIGIKOST-FFQ is a food frequency questionnaire aiming to benchmark against the Norwegian food-based dietary guidelines. | From baseline (T0) to 24 weeks (T2) | 
| Change in adherence to the Norwegian food-based dietary guidelines assessed by DIGIKOST-FFQ | DIGIKOST-FFQ is a food frequency questionnaire aiming to benchmark against the Norwegian food-based dietary guidelines. | From baseline (T0) to 36 weeks (T3) | 
| Change in general health measured by European Quality of Life Five-Dimension Scale Questionnaire (EQ-5D) | EQ-5D consists of five dimensions (mobility, self-care, usual activities, pain & discomfort, anxiety & depression), each of which has five severity levels that are described by statements appropriate to that dimension. | From baseline (T0) to 12 weeks (T1) | 
| Change in general health measured by European Quality of Life Five-Dimension Scale Questionnaire (EQ-5D) | EQ-5D consists of five dimensions (mobility, self-care, usual activities, pain & discomfort, anxiety & depression), each of which has five severity levels that are described by statements appropriate to that dimension. | From baseline (T0) to 24 weeks (T2) | 
| Change in general health measured by European Quality of Life Five-Dimension Scale Questionnaire (EQ-5D) | EQ-5D consists of five dimensions (mobility, self-care, usual activities, pain & discomfort, anxiety & depression), each of which has five severity levels that are described by statements appropriate to that dimension. | From baseline (T0) to 36 weeks (T3) | 
| Change in quality of life among the relatives measured by Research and Development 36-term Short Form Health Survey (RAND SF-36) | RAND-36 comprises 36 items that assess eight health concepts: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, emotional well-being, energy/fatigue, pain, and general health perceptions. Physical and mental health summary scores are also derived from the eight RAND-36 scales.All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. | From baseline (T0) to 12 weeks (T1) | 
| Change in quality of life among the relatives measured by Research and Development 36-term Short Form Health Survey (RAND SF-36) | RAND-36 comprises 36 items that assess eight health concepts: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, emotional well-being, energy/fatigue, pain, and general health perceptions. Physical and mental health summary scores are also derived from the eight RAND-36 scales.All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. | From baseline (T0) to 24 weeks (T2) | 
| Change in quality of life among the relatives measured by Research and Development 36-term Short Form Health Survey (RAND SF-36) | RAND-36 comprises 36 items that assess eight health concepts: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, emotional well-being, energy/fatigue, pain, and general health perceptions. Physical and mental health summary scores are also derived from the eight RAND-36 scales.All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. | From baseline (T0) to 36 weeks (T3) | 
| Change in quality of life among the relatives measured by the global health status / QoL scale from the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). | The questionnaire includes a global health status / quality of life (QoL) scale, which range in score from 0 to 100. A high score for the global health status / QoL represents a high QoL. | From baseline (T0) to 12 weeks (T1) | 
| Change in quality of life among the relatives measured by the global health status / QoL scale from the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). | The questionnaire includes a global health status / quality of life (QoL) scale, which range in score from 0 to 100. A high score for the global health status / QoL represents a high QoL. | From baseline (T0) to 24 weeks (T2) | 
| Change in quality of life among the relatives measured by the global health status / QoL scale from the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). | The questionnaire includes a global health status / quality of life (QoL) scale, which range in score from 0 to 100. A high score for the global health status / QoL represents a high QoL. | From baseline (T0) to 36 weeks (T3) | 
| Cost-effectiveness calculated based on measurements of health-related QoL and resource use (costs related to the intervention. | Combining information about health-related QoL will give quality-adjusted life-years, while valuation of resource use using standard principles of health economic evaluation will provide estimates of costs | From baseline (0) to 36 weeks (T3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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physical activity, nutrition, patient education, lymphoma, cancer survivorship, cognitive behavioral program