Impact of Respiratory Training in Lymphoma Survivors

Study Overview
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Brief Summary
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High-resistance inspiratory muscle strength training (IMST) is a time-efficient ( 5 minutes/day) form of exercise that employs an affordable, handheld device which impedes inspiratory breathing to train the diaphragm and accessory respiratory muscles and has demonstrated improvements in both cardiovascular health (9 mmHg reduction in systolic blood pressure, 45% improvement in vascular endothelial function) and improve exercise tolerance (12% increase in treadmill exercise time) in generally healthy midlife/older adults. Therefore, this approach may circumvent preventative hurdles to exercise, and augment the effects of exercise for capable survivors.

Detailed Description
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Cancer survivorship has been steadily improving as a result of earlier detection and improved therapies. Behind cancer recurrence, the primary cause of morbidity and mortality among survivors stems from the onset of cardiovascular disease that arises in part due to cardiotoxic chemo and radiation therapies. The increased risk of cardiovascular disease is particularly high in specific survivor populations, such as lymphoma survivors. Although exercise has been demonstrated to improve both recovery after cancer therapy and quality of life, both physical and logistical hurdles may prohibit certain patients from accessing this intervention. High-resistance inspiratory muscle strength training (IMST) is a time-efficient ( 5 minutes/day) form of exercise that employs an affordable, handheld device which impedes inspiratory breathing to train the diaphragm and accessory respiratory muscles and has demonstrated improvements in both cardiovascular health (9 mmHg reduction in systolic blood pressure, 45% improvement in vascular endothelial function) and improve exercise tolerance (12% increase in treadmill exercise time) in generally healthy midlife/older adults. Therefore, this approach may circumvent preventative hurdles to exercise, and augment the effects of exercise for capable survivors.

Official Title
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The Impact of Inspiratory Muscle Strength Training and Personalized Exercise Prescription on Metabolism, Cardiovascular Function, and Cardiorespiratory Fitness in Lymphoma Survivors

Conditions
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Hodgkin Lymphoma, Non Hodgkin Lymphoma

Intervention / Treatment
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* Device: Inspiratory muscle strength training
* Device: Sham Inspiratory muscle strength training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 80 Primary cancer diagnosis of lymphoma Able and willing to participate in a supervised exercise program at the Anschutz Health and Wellness Center Provides a signed physician exercise clearance form SBP > 120 mmHg Completion of curative cancer treatment over 12 months prior (individuals on maintenance therapy will be included) Possession of a smartphone compatible with the IMST training application (available on both Android and Apple). Exclusion Criteria: oSecond active cancer diagnosis oPlanned active cancer treatment or change in current treatment in the next 6 months Severe obesity (BMI > 40 kg/m2) or underweight (BMI < 18.5 kg/m2) Unstable weight (> 3 kg change in body mass in last 3 months) Significant metabolic disorder (e.g. diabetes type II) Uncontrolled thyroid disease Recent changes in hypertensive medication (within last 3 months) Greater than 100 min of self-reported regular exercise per week Any medical condition that would impact the safety of, or participation in, an exercise program, including: Significant pulmonary conditions such as chronic obstructive pulmonary disease, emphysema, or interstitial lung disease Known cardiovascular disease, significant hypertension (> 180/120), or a recent cardiac event (within past 6 months) Orthopedic conditions such as advanced osteoarthritis, mobility-limiting amputations or chronic injuries, or mobility-limiting acute orthopedic injuries Advanced rheumatoid arthritis or chronic widespread pain conditions such as fibromyalgia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lymphoma Survivors IMST<br>Participants will undergo a version of the BfitBwell Cancer Exercise Program physical assessment, which assesses physical fitness and function. | Device: Inspiratory muscle strength training<br>* High-resistance inspiratory muscle strength training (IMST) is a time-efficient ( 5 minutes/day) form of exercise that employs an affordable, handheld device which impedes inspiratory breathing to train the diaphragm and accessory respiratory muscles<br>* Other names: IMST;|
| Experimental: Lymphoma Survivors sham IMST<br>Participants will undergo a version of the BfitBwell Cancer Exercise Program physical assessment, which assesses physical fitness and function. | Device: Sham Inspiratory muscle strength training<br>* Low-resistance inspiratory muscle strength training<br>* Other names: Sham IMST;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Participants Recruited | Count of number of participants recruited into the study | 2 years | 
| Enrolled Participants per Month | Average number of participants enrolled per month of the study | 2 years | 
| Valid Assessments per Participant | Adherence to 75% of the program will be deemed acceptable | 5 months | 
| Session Attendance per Participant | Adherence to 75% of the program will be deemed acceptable | 5 months | 
| Total Participants Completing the Intervention | Adherence to 75% of the program will be deemed acceptable | 2 years | 
| Systolic Blood Pressure | Resting systolic blood pressure, collected in triplicate | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular Markers - Acetylcholine-stimulated production of nitric oxide | Serum will be used to perform experiments in which purchased cultured endothelial cells will be exposed to 10% serum from human subjects for 24 hours. The investigators will measure acetylcholine-stimulated production of nitric oxide (NO) in endothelial cells following serum incubation. Serum will be collected via venipuncture performed at the CTRC and stored at -80°C until analysis. | 5 months | 
| Molecular Markers - Acetylcholine-stimulated basal reactive oxygen species production | Serum will be used to perform experiments in which purchased cultured endothelial cells will be exposed to 10% serum from human subjects for 24 hours. The investigators will measure acetylcholine-stimulated basal reactive oxygen species (ROS) production in endothelial cells following serum incubation. Serum will be collected via venipuncture performed at the CTRC and stored at -80°C until analysis. | 5 months | 
| Cardiorespiratory Fitness (CRF) will be assessed via estimated VO2max | This will be measured by the Tecumseh Step Test. Participants step on and off an 8 step for 3 min, at a metronome-controlled pace of 24 steps/min. Afterward, they immediately sit down, and heart rate is recorded at 30 s and 1 min after completion (using Polar F4 heart rate monitors). These recovery heart rates are then entered into a predictive formula, along with patient biometric information (age, weight, gender), to calculate an estimated VO2max. | 5 months | 
| Physical function primarily assessed by the 6MWT | Participants will be instructed to walk as far as possible in a six minute period on an indoor track. | 5 months | 
| Metabolomics analyses will be performed on blood samples | Metabolomics analyses will be performed on blood samples collected during a standardized aerobic exercise session. Samples will be collected before exercise, immediately after, and after 30 min of recovery. Samples will be collected with patient-centric Tasso+ devices (Tasso, Inc) which minimize the discomfort of collection. | 5 months | 
| Functional Assessment of Cancer Therapy - General (FACT-G, assessing quality of life) | A 27-item scale commonly used to assess overall quality of life in the general cancer survivor population. Scores range from 0-108 with higher scores indicate higher quality of life. | 5 months | 
| Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) | A 13-item scale commonly used to assess cancer-related fatigue in cancer survivors. Scores range from 0-52 with higher scores indicate lower levels of fatigue. | 5 months | 
| Godin Leisure Time Physical Activity Questionnaire | A 6-item scale asking participants the amount of time spent in light, moderate, and vigorous physical activity during the past week. Scores start at 0 with no upper range. Higher scores indicate more minutes of activity per week. | 5 months | 
| Hospital Anxiety and Depression Scale (HADS) | 14 item scale indicating levels of anxiety and depression in clinical populations. Scores range from 0-21 for anxiety and depression scales. Higher scores indicate higher levels of anxiety and depression. | 5 months | 
| Cardiac risk factors will be collected from medical history forms | These risk factors will be included in secondary analyses to assess if participants at higher known risk of cardiac disease differ in their response to the intervention. | 5 months |