Treatment for Persistently Fatigued Cancer Survivors: A Randomized Controlled Trial With Biomarker Response

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects of Mindfulness-Based Stress Reduction (MBSR) to an attention control psycho-educational support group in treating cancer-related fatigue (CRF) in early-stage (0-III) post-treatment cancer survivors with clinically-significant CRF. The study will collect, store, and later analyze blood and urine samples for several biomarkers that may be linked to persistent CRF in cancer survivors.

Detailed Description
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This is a randomized, attention control clinical trial to compare MBSR to support and education on biobehavioral outcomes in early-stage (0-III) post-treatment cancer survivors with clinically-significant CRF. The study will use quantitative and qualitative methods to evaluate the following: Primary Aim 1: Determine effect size estimates of MBSR compared to attention control in reducing fatigue interference and the severity of several cancer-related symptoms immediately post-intervention and at 6-month follow-up. Exploratory Aim 1: To identify potential moderators of intervention effects in breast cancer survivors (BCS) and colorectal cancer survivors (CRCS), such as demographic, clinical/disease characteristics, personality traits, and baseline mindfulness level. Exploratory Aim 2: To compare levels of a number of anti- and pro-inflammatory proteins present in blood and urine between MBSR and attention control groups immediately post-intervention and 6-month follow-up, and between fatigued and non-fatigued breast cancer survivors at baseline.

Official Title
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Treatment for Breast and Colorectal Cancer Survivors With Persistent Cancer-Related Fatigue: A Randomized Controlled Trial

Conditions
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Fatigue

Intervention / Treatment
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* Behavioral: Mindfulness-Based Stress Reduction
* Behavioral: Attention Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for breast cancer participants: be age 18 or older live in the Indianapolis region have an established first-time diagnosis of non-metastatic (stages 0-III) breast cancer treated with chemotherapy and/or radiation therapy be in good general health (self-report) have clinically-significant CRF (Fatigue Symptom Inventory [FSI severity composite ≥ 4]) that has persisted for the previous 8 weeks or longer. Inclusion Criteria for colorectal cancer participants: be age 18 or older live in the Indianapolis region have an established diagnosis of colorectal cancer (any stage) in treatment currently or previously with chemotherapy and/or radiation therapy have clinically-significant CRF (Fatigue Symptom Inventory [FSI severity composite ≥ 4) that has persisted for the previous 8 weeks or longer. Exclusion Criteria for breast cancer participants: cancer treatment (chemotherapy, biologic response modifiers, radiation therapy, or surgery) in prior 3 months or > 5 years ago (endocrine therapy for breast cancer is allowed) enrollment in hospice care severe depression (PHQ-8 ≥ 20) past participation in a mindfulness meditation class and/or having an established/ongoing meditation practice Exclusion Criteria for colorectal cancer participants: enrollment in hospice care severe depression (PHQ-8 ≥ 20) past participation in a mindfulness meditation class and/or having an established/ongoing meditation practice A non-fatigued group of post-treatment BCS will also be enrolled in order to compare baseline levels of all biomarkers and all self-reported psychosocial measures between fatigued and non-fatigued BCS. Inclusion criteria for non-fatigued BCS participants being age 18 or older having an established first-time diagnosis of non-metastatic (stage 0-III) breast cancer being in good general health (self-reported) having FSI severity composite scores of ≤ 2 Exclusion criteria for non-fatigued BCS participants cancer treatment (chemotherapy, biologic response modifiers, radiation therapy, or surgery) in prior 3 months or > 5 years ago (endocrine therapy for breast cancer is allowed) enrollment in hospice care severe depression (PHQ-8 ≥ 20)

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mindfulness-Based Stress Reduction<br>The MBSR intervention is an 8-week course meeting 2 hours weekly. The curriculum is based on MBSR manuals with a brief CRF education component incorporated into the first and second class sessions, drawing from information from the National Comprehensive Cancer Network clinical practice guidelines for CRF. In general, the MBSR class includes guided meditation practice; mindful, gentle movement (hatha yoga); didactic material on self-regulatory responses to stress; and group discussion that includes the participants' growing incorporation of mindfulness in adapting to life experiences. Along with class time, each participant is asked to commit 20 minutes per day, six days per week to formal meditation practice using compact disk recordings of the teacher's voice. | Behavioral: Mindfulness-Based Stress Reduction<br> <br> * Other names: MBSR;|
| Active Comparator: Attention Control<br>The attention control is an 8-week class meeting 2 hours weekly. The group sessions are supportive in tone, focus on pre-designated topics relevant to fatigue management (e.g., sleep hygiene, nutrition, exercise, emotional regulation), and involve weekly readings and open group discussion about session topics. This condition contains non-specific factors similar to MBSR (e.g., facilitator offering participants compassionate attention, empathy, genuine caring, and an opportunity to discuss what is important to them in a supportive environment); however, mindfulness is not presented/practiced in the group. | Behavioral: Attention Control<br> <br> * Other names: Education/support group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cancer-related fatigue functional interference | The Fatigue Symptom Inventory interference subscale will be used to assess the degree to which CRF was judged to interfere with quality of life across seven domains over the previous week. | from baseline to 6 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cancer-related fatigue severity | The Fatigue Symptom Inventory severity subscale will be used to assess the most, least, and average fatigue in the past week, as well as current fatigue. | from baseline to 6 month follow-up | 
| Change in vitality | The Short Form (36) Health Survey Vitality Scale will be used to assess how much during the past 4 weeks the person had a lot of energy, felt full of life, felt worn out, and felt tired. | from baseline to 6 month follow-up | 
| Change in depression | The PHQ-8 scale will be used to assess how often the person has been bothered over the previous 2 weeks by symptoms of depression, including little interest or pleasure in doing things and feeling down, depressed, or hopeless. | from baseline to 6 month follow-up | 
| Change in anxiety | The GAD-7 scale will be used to assess how often the person has been bothered over the previous 2 weeks by symptoms such as: feeling nervous, anxious, or on edge; not being able to stop or control worrying; and trouble relaxing. | from baseline to 6 month follow-up | 
| Change in sleep disturbance | The Insomnia Severity Index will be used to assess the perceived severity of insomnia and the impact of sleep difficulties over the previous 2 weeks. | from baseline to 6 month follow-up | 
| Change in pain | The Brief Pain Inventory-3 is a brief pain measure derived from the Brief Pain Inventory. It is also known as the PEG and will be used to assess average pain intensity (P), interference with enjoyment of life (E), and interference with general activity (G) over the past week. | from baseline to 6 month follow-up | 
| Change in fear of recurrence | The Concerns About Recurrence Scale will be used to assess overall frequency, potential for upset, consistency, and intensity of recurrence fears. | from baseline to 6 month follow-up | 
| Change in attentional function | The Attentional Function Index will be used to assess perceived effectiveness in common activities requiring attention and working memory. | from baseline to 6 month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Fatigue, Mindfulness, Meditation, Neoplasms, Signs and symptoms