Improving Exercise Capacity With a Tailored Physical Activity Intervention

Study Overview
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Brief Summary
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The purpose of this research is to test whether participating in either a physical activity intervention or a series of educational classes will help to preserve exercise capability, heart function, brain-based activities (like memory), and quality of life. Participants will be randomized to 1 of 2 pathways: First pathway consists of organized health workshops. These workshops are intended to provide information on topics such as proper nutrition, management of stress, sleep practices, and emphasis on a healthy lifestyle that may help the participants through cancer treatment. This pathway will also test whether stretching may help participants through cancer treatment. Second pathway participants will take part in some unsupervised and some potentially supervised moderate activity sessions each week throughout participants' cancer treatment to take place either remotely or in person, depending on availability of facilities at the time visits are scheduled.

Detailed Description
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Primary Objective: To determine if a >10% difference exists in the % change (i.e., 2.06 ml/kg/min difference) in peak VO2 (volume or amount of oxygen your body consume) from baseline to 6 months of intervention between participants receiving the Physical Activity Intervention (PAI) versus Healthy Living Intervention (HLI). Secondary Objectives: To determine if a >10% difference exists in the % change in peak exercise cardiac output, calculated A-VO2 difference, and pre-exercise measures of left ventricular function from baseline to 6 months of intervention between participants receiving the PAI versus HLI. Among these same participants, 1) to compare PAI and HLI groups on their baseline to 3 & 6 months after initiating cancer treatment changes in 6-minWD, Health-Related Quality of Life (HRQOL), fatigue, strength, physical activity, cognitive & physical function, 2) to determine the relationships between the 6-month time-dependent changes in these and peak VO2; and 3) to examine whether time-dependent changes in peak exercise cardiac output and/or calculated arteriovenous oxygen difference are associated with similar time-dependent changes in peak VO2. Assess physical activity engagement via accelerometry.

Official Title
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Improving Exercise Capacity With a Tailored Physical Activity Intervention in Lymphoma Patients Undergoing Treatment

Conditions
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Non Hodgkin Lymphoma, Heart; Functional Disturbance, Hodgkin Lymphoma, Quality of Life

Intervention / Treatment
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* Other: Exercise with Trainerize application
* Diagnostic Test: Cardiopulmonary exercise testing
* Diagnostic Test: MRI scan
* Behavioral: Quality of Life Questionnaires
* Behavioral: Cognitive and Brain Function Questionnaires
* Other: Blood draws


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be considered eligible, participants must meet all of the following criteria: Individuals aged 18- 85 years Diagnosed with stage I-IV Hodgkin's or non-Hodgkin's lymphoma Expected to receive an anthracycline based chemotherapeutic regimen or other potentially cardiotoxic cancer therapies (e.g. chemotherapy regimens [anthracyclines, trastuzumab]), immuno-therapies (immune checkpoint inhibitors [ICI's]) or radiation (within 8 weeks of completion of radiation).29-31 Ability to speak and understand English Capacity to walk at least 2 city blocks ( .2 miles) on a flat surface Expected survival beyond 6 months. Must have an assistant that will help perform the home-based testing activities Exclusion Criteria: If the patient meets any of these criteria they are excluded from the study: Uncontrolled hypertension (systolic blood pressure >190 mm Hg or diastolic blood pressure >100 mm Hg) Recent history of alcohol or drug abuse, inflammatory conditions such as lupus or inflammatory bowel disease, or another medical condition that might compromise safety or successful completion (unless approved by the participant's physician and the Principal Investigator) NOTE: In the setting of active inflammation, participation will not be approved. If chronic disease is present and stable as judged by the participant's physician and the PI, participation will be approved. Contraindications to MRI such as ferromagnetic cerebral aneurysm clips or other intracranial metal, pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices (unless approved by the participant's physician and the Principal Investigator) Claustrophobia Pregnant Unstable angina Contraindication for exercise training or testing Inability to exercise on a treadmill or stationary cycle Significant ventricular arrhythmias (>20 PVCs/min due to gating difficulty) Atrial fibrillation with uncontrolled ventricular response Acute myocardial infarction within 28 days Inability to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Physical Activity Intervention<br>Participants will have the ability to attend one to two training sessions per week and 1-2 sessions per week at home (the 4th level of our multi-level intervention) or the location site using the Trainerize application to deliver the exercise prescription. | Other: Exercise with Trainerize application<br>* 1-2 sessions per week consisting of slow 15 minute aerobic warm, 20 minutes of strength training, 15 minutes progressive intensity aerobic exercise and 10 minute cool down (stretching/toning) with elastic bands.<br>Diagnostic Test: Cardiopulmonary exercise testing<br>* Maximal peak VO2 (to monitor the body's oxygen consumption) and 6-minute exercise walking test.<br>Diagnostic Test: MRI scan<br>* Images of the heart will be taken.<br>Behavioral: Quality of Life Questionnaires<br>* Participants will be asked to complete several questionnaires that will measure fatigue, general health, social determinants of health, cognitive function (tasks that assess memory, ability to count, etc.) and physical activity. The questionnaires will take 15-40 minutes to complete.<br>Behavioral: Cognitive and Brain Function Questionnaires<br>* Participants will be asked to complete several questionnaires that will measure fatigue, general health, social determinants of health, cognitive function (tasks that assess memory, ability to count, etc.) and physical activity. The questionnaires will take 15-40 minutes to complete.<br>Other: Blood draws<br>* Approximately 2 teaspoons of blood withdrawn from either a vein in your arm or a currently placed central line port-a-cath. A portion of blood from each visit will be used to collect information about blood cell count.<br>|
| Experimental: Healthy Living Intervention (Control Arm)<br>Participants randomized to the control arm will participate in organized health workshops. Each session will last 60 minutes and will be offered on location and virtually (e.g., Zoom) over 6 months. Participants will meet once a week for the first 4 weeks, biweekly for 3 months, and once a month for the last 2 months for a total of 12 sessions. | Diagnostic Test: Cardiopulmonary exercise testing<br>* Maximal peak VO2 (to monitor the body's oxygen consumption) and 6-minute exercise walking test.<br>Diagnostic Test: MRI scan<br>* Images of the heart will be taken.<br>Behavioral: Quality of Life Questionnaires<br>* Participants will be asked to complete several questionnaires that will measure fatigue, general health, social determinants of health, cognitive function (tasks that assess memory, ability to count, etc.) and physical activity. The questionnaires will take 15-40 minutes to complete.<br>Behavioral: Cognitive and Brain Function Questionnaires<br>* Participants will be asked to complete several questionnaires that will measure fatigue, general health, social determinants of health, cognitive function (tasks that assess memory, ability to count, etc.) and physical activity. The questionnaires will take 15-40 minutes to complete.<br>Other: Blood draws<br>* Approximately 2 teaspoons of blood withdrawn from either a vein in your arm or a currently placed central line port-a-cath. A portion of blood from each visit will be used to collect information about blood cell count.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peak VO2 | An analysis of covariance (ANCOVA) model will be used to assess post-intervention group differences in VO2, adjusted for baseline peak VO2. | At baseline and 6 months after study intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peak Exercise Cardiac Output | Measured on a continuous scale and will be analyzed using a repeated measures ANCOVA (RMANCOVA) approach. | At baseline and 6 months after study intervention | 
| Change in Calculated A-V Oxygen Levels | Measured on a continuous scale and will be analyzed using a repeated measures ANCOVA (RMANCOVA) approach. | At baseline and 6 months after study intervention | 
| Changes in Measurements of Pre-exercise Left Ventricular Function | Measured on a continuous scale and will be analyzed using a repeated measures ANCOVA (RMANCOVA) approach. | At baseline and 6 months after study intervention | 
| Change in Neurocognitive Function - Hopkins Verbal Learning Test | The Hopkins Verbal Learning Test (HVLT-R) consists of memorization of a list of words to test the ability to recall immediately after memorization (immediate recall) and after a 20-minute delay (delayed recall). This test has three parts and two alternate forms. Total scores could range from 0 to 30. Lower raw scores indicate difficulties with the task. | At baseline and 6 months after study intervention | 
| Change in Neurocognitive Function - Controlled Oral Word Association Test (COWAT) | The Controlled Oral Word Association Test is a verbal fluency test in which participants are asked to say as many words as possible from a given category and in a specified timeframe (typically 60 seconds). COWAT is measured by calculating the total number of acceptable words produced for at the given letter of the alphabet. Errors and perseverations (word repetitions) are not included in this score. | At baseline and 6 months after study intervention | 
| Change in Neurocognitive Function - Digit Span-Backward Test | The digit span backward test is used to assess working memory. Participants are given a series of digits and asked to repeat them backward. The item score is the sum of the scores on the two trials for that item (range=0-2). The total raw score for backwards digit span is the sum of the item scores; maximum backwards digit span total raw score is 16 points. | At baseline and 6 months after study intervention | 
| Change in Neurocognitive Function - Trail Making Test | The Trail Making Test (TMT) asks patients to connect consecutive targets (numbers and/or letters) on a page arranged in a specific geometric pattern. Scoring is based on time taken to complete the test (e.g. 35 seconds yielding a score of 35) with lower scores being better. | At baseline and 6 months after study intervention | 
| Change in 6-Minute Walk Distance | Measured on a continuous scale and will be analyzed using a repeated measures ANCOVA (RMANCOVA) approach. | At baseline, 3 months and 6 months after study intervention | 
| Health-Related Quality of Life Questionnaire (FACT-Lym) | 42-item questionnaire to assess the quality of life for lymphoma patients. 5-point Likert scale - 0 (not at all) to 4 (very much). Subscale domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, Lymphoma Subscale. Some items are reverse scored. Subscales scores are added to get the total score. The higher the score, the better the quality of life. Scores can range from 0-168 | At baseline, 3 months and 6 months after study intervention | 
| Fatigue Questionnaire | Questionnaire to assess the difference in the level of fatigue participants experience will performing study interventions. 5-point Likert scale - 0 (not at all) to 4 (very much). The higher the score the higher level of fatigue participants experience. Score range 0-52. | At baseline, 3 months and 6 months after study intervention | 
| Change in Physical Activity Levels - Godin Leisure Time Exercise Questionnaire | The questionnaire is a 4-item measure used to classify participants' activity levels during a typical 7-day period based on how many times on average participants exercise more than 15 minutes during their free time of strenuous, moderate or mild exercise. | At baseline, 3 months and 6 months after study intervention | 
| Change in Physical Function - Balance Test | Participants will be asked to maintain balance for up to 30 seconds in three positions characterized by a progressive narrowing of the base support: heel of one foot beside the big toe of the other foot (semi-tandem position), heel of one foot in front of and touching the toes of the other foot (tandem position), and single leg stand. | At baseline, 3 months and 6 months after study intervention | 
| Change in Physical Function - Chair Stand Test | The repeated chair stand test will be performed using a straight-backed chair placed with its back against a wall. Participants will be first asked to stand from a sitting position without using their arms. If they can perform the task, they will then be asked to stand up and sit down five times as quickly as possible. The time to complete the task will be recorded. | At baseline, 3 months and 6 months after study intervention | 
| Change in Physical Function - 4-Meter Walk Gait Speed Test | The gait speed test will assess the participant's ability to walk 4 meters. Participants will be instructed to start at a marked walking course with toes touching the start line and when cued to start, will begin walking at their usual speed. The time to walk from the starting line to the end of the 4-meter walk will be recorded | At baseline, 3 months and 6 months after study intervention | 
| Change in Physical Function - Grip Strength | Grip strength will be assessed using an isometric handgrip dynamometer while the participant is seated with the head facing straight ahead. The elbow should be bent at a 90 degree angle and the wrist should be at the mid-prone position. The participant should exert maximally and quickly (about 1 second) and two trials should be made alternately with each hand, with at least 30 seconds between trials for the same hand (recorded in kilograms). | At baseline, 3 months and 6 months after study intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise capability, Brain activity