Remotely Monitored, Mobile Health-supported, High Intensity Interval Training Before Hematopoietic Stem Cell Transplant
- Conditions
- Hematopoietic Stem Cell TransplantationCardiorespiratory Fitness
- Registration Number
- NCT06953648
- Lead Sponsor
- University of Kansas Medical Center
- Brief Summary
The goal of this clinical trial is to learn how a remotely monitored high-intensity interval training (REMM-HIIT) affects the cardiorespiratory fitness and physical function for patients planning to undergo stem cell transplantation. The main questions it aims to answer are:
Is there a change in the participant's cardiorespiratory fitness level? Is there a change in the participant's physical function?
Researchers will compare the REMM-HIIT program to a control group of participants who do not take part in the training program to see if REMM-HIIT helps improve stem cell transplantation outcomes.
Participants will:
* Complete cardiopulmonary exercise testing (CPET) 4 times during the study
* Do basic tests to measure physical function 6 times during the study
* Answer questions about their life and how they are feeling 6 times during the study
* Wear a device to keep track of step counts and heart rate daily
* Keep a log of every time they exercise throughout the study
* Optionally, provide blood and stool samples 6 times during the study
- Detailed Description
Each year in the U.S., approximately 8,000 patients undergo allogeneic hematopoietic stem cell transplantation (HCT) as a potentially curative therapy for leukemias, lymphomas, and other hematologic malignancies. However, treatment-related mortality (TRM) is significant, ranging from 10-30%. Moreover, survivors of HCT often face significant physical, psychological, and social challenges post-treatment, leading to a substantial decrease in quality of life (QOL). Outcomes are closely linked to pre-HCT physical activity and function. For example, patients with worse pre-HCT physical function and capacity have markedly lower one-year survival rates (50% vs. 83%). In contrast, every 50-meter increase in pre-HCT six-minute walk distance (6MWD) correlates with a 9% reduction in relative risk for mortality.
Cardiorespiratory fitness (CRF) is a crucial indicator of physical capacity, reflecting the integrated functioning of the heart, lungs, skeletal muscle, adipose tissue, pancreas, liver and adrenal tissues. While CRF naturally declines with age, this decline is notably accelerated by cancer and its treatments, with cancer patients' average CRF levels comparable to individuals 20-30 years older. Importantly, patients with low pre-HCT CRF (VO2peak \<16 mL/kg/min) are at much higher risk of TRM (hazard ratio 6.70), even after accounting for other risk factors. This underscores the critical need for interventions to improve CRF prior to HCT to enhance survival and post-treatment quality of life.
It is well established that patients with better pre-HCT physical function tend to have better post-HCT outcomes. The critical question, however, is whether enhancing fitness pre-HCT can improve post-HCT outcomes. Animal studies provide optimism: exercise training in a murine model pre-HCT associated with improved survival, possibly through immune-mediated pathways. Yet, research exploring the impact of pre-HCT exercise on human post-HCT outcomes remains limited. Small studies have linked pre-HCT improvements in physical function with better survival, and preliminary results from a randomized controlled trial suggest that exercise during HCT may reduce mortality. However, a recent large (n=711) randomized Blood and Marrow Transplant Clinical Trials Network study of self-directed exercise and stress management during HCT did not show a significant benefit in outcomes. Study investigators suggested several reasons for this lack of effect, including timing of intervention (peri-HCT rather than pre-HCT), low intensity rather than high intensity exercise, and low engagement in the self-directed program.
To address prior study limitations, the investigators developed the REMM-HIIT program, focusing on pre-HCT intervention, high-intensity interval training (HIIT), and a mobile health (mHealth) platform to support participant engagement. This program, supported by the National Institute of Aging and the Duke Claude D. Pepper Older Americans Independence Center, was piloted in a successful phase 1 study of Remotely Monitored, Mobile health-supported, pre-HCT High Intensity Interval Training (REMM-HIIT). In this feasibility study, participants underwent baseline cardiopulmonary exercise testing (CPET) to ensure cardiac safety and to measure maximal cardiorespiratory fitness (VO2peak). The heart rate (HR) at VO2peak was used to personalize the high and low intensity interval goals. Participants were equipped with an iPhone and Garmin Watch for remote monitoring and exercised three times a week at home, with the first session and subsequent sessions as needed monitored remotely by the coach via videoconference. This approach ensured continuous support and maximized participant engagement while allowing the majority of sessions to occur remotely.
This program was purposely designed based on investigators' prior research and other significant studies in the field, aiming to overcome common barriers to physical activity in cancer populations. To facilitate participation, the investigators enable exercise at home utilizing the participant's preferred activity (e.g., walking, cycling, stairs) and at convenient times. The majority engaged in walking-based intervention, which despite their simplicity, provided sufficient intensity for deconditioned HCT participants. Others used cycle ergometers. This program adheres to the principles of exercise training and recommendations from Sasso and colleagues, ensuring individualization, progressive overload, appropriate recovery periods, and reasonable specificity. Exercise sessions started with a 5-minute warmup (e.g., walking or cycling at a HR corresponding to 60% VO2peak). This was followed by ten intervals, each consisting of one-minute of high intensity exercise at a HR corresponding to 95% VO2peak, alternated with one minute of low to moderate intensity interval at a HR corresponding to 60% VO2peak, totaling 20 minutes. The session concluded with a 5-minute cooldown, resulting in a comprehensive 30-minutes exercise session. For participants unable to complete all intervals, the study team began with fewer intervals and gradually increased the number as tolerated. A recovery period of 24-48 hours between HIIT sessions was recommended to prevent overtraining and ensure adequate recovery. Broad specificity was achieved by incorporating high, moderate, and low intensity aerobic exercises continuously. As such, the program is a progressive HIIT-based intervention, with flexibility given to ensure the principles of exercise training are upheld, and participants receive the best possible information and guidance to rapidly increase CRF and health outcomes pre-HCT.
The investigators' prior phase 1 study was successful. Out of 24 participants approached, 14 enrolled (10 males, 4 females), achieving a recruitment rate of 58%. Of the 14 enrolled, 13 (age 59±12, range 34-76 yrs; 10 White, 3 Black) were medically cleared to proceed with HIIT following a CPET. One participant did not proceed to HIIT and was withdrawn due to cardiac concerns detected on baseline CPET. Importantly, there were no adverse events associated with exercise among the remaining participants. Participants were able to engage in HIIT, even with a baseline CRF as low as 10.6 mL/kg/min; for reference, independent living in healthy adults is generally associated with a CRF \>18 in men and \>15 in women. Some participants who were habitually exercising were able to complete ten intervals immediately and to maintain intensity over time, while other participants who were less fit required more coaching but were able to rapidly improve fitness to reach program goals. Remarkably, even with low baseline CRF and concomitant chemotherapy (some requiring hospitalization), nine of the 13 participants engaged in the exercise program (69%), and average adherence to the prescribed 3 sessions/week in those nine was excellent at 104 +/- 28%. Mean intervention length was 13.8 +/- 7.5 weeks, with participants staying engaged in the exercise program for approximately three months prior to HCT; this compares very favorably to the 50-70% adherence rates commonly reported in other home-based exercise studies. All 7 participants who had repeat CPET showed improvements in CRF, with average change in VO2peak from 14.6 ± 3.1 mL/kg/min at enrollment to 17.9 ± 3.3 by the start of transplant, or 23% increase (p\<0.001). For the other 6, 3 were not evaluated due to the onset of the COVID-19 pandemic, which suspended research operations. Because CRF declines at about 10% per decade, this substantial improvement in CRF equates to a fitness level increase that typically would take over 20 years to achieve, aligning participants' fitness more closely with that of healthy adults34. As highlighted by Wood et al.,16 a pre-HCT VO2peak \<16 mL/kg/min is associated with higher post-HCT mortality rate (HR 6.70 (1.29-34.75), p=0.02) and longer hospital stay (median number of hospitalized days before Day 100: 33 vs. 21, p=0.004). Thus, increasing CRF pre-HCT has the potential to improve post-HCT outcomes, suggesting this program could substantially impact participant health and recovery.
The investigators believe this program's success is from a combination of participant motivation and mHealth platform and coaching. Because participants know that they were to undergo HCT within a few months, with a 10-30% chance of death related to the treatment itself, they were highly motived to do anything they could to improve their chances of survival. Furthermore, knowing that an oncology-experienced exercise professional is monitoring their exercise sessions, coupled with personalized and frequent feedback (at least once a week), likely helped improve adherence, with resultant improvements in CRF.
Allogeneic HCT has curative potential for hematologic malignancies but is associated with significant morbidity and TRM, especially in patients with low pre-HCT CRF. Improving CRF through a time-efficient, high-intensity interval training (HIIT) approach, facilitated remotely via mHealth, could improve physical function and clinical outcomes for HCT patients. The investigators hypothesize that patients undergoing REMM-HIIT program will experience improved CRF, physical function, and QOL pre-HCT, leading to better post-HCT outcomes, including improved physical function, reduced TRM, and increased overall survival.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 126
- Plan to undergo allogeneic hematopoietic stem cell transplant in 4-12 weeks after enrollment on this study.
- Age 18-80 years
- Able to read/write English (as many participant-reported outcome measures lack validated translations in other languages)
-
Unable or unwilling to follow coaching
-
Functional impairment resulting in inability to exercise
-
Any absolute contraindications to exercise:
- recent (<6 months) acute cardiac event;
- unstable angina;
- uncontrolled dysrhythmias causing symptoms;
- symptomatic aortic stenosis;
- uncontrolled symptomatic heart failure;
- acute pulmonary embolus;
- acute myocarditis or pericarditis;
- suspected or known dissecting aneurysm
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Change in Cardiorespiratory Fitness At Baseline, Day -10, Day 90, and Day 365 Change in cardiorespiratory fitness as measured by the difference in peak rate of oxygen consumption (VO2peak) in mL/(kg\*min) from baseline to the pre-hematopoietic stem cell transplant (HCT) timepoint; a higher number for VO2 peak indicates greater cardiorespiratory fitness.
Change in Physical Function (Six Minute Walk Test Distance) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 The change in physical function as measured by the difference in six minute walk test distance in meters from baseline to the pre-hematopoietic stem cell transplantation (HCT) timepoint; a greater number of meters walked indicates a higher level of physical function.
- Secondary Outcome Measures
Name Time Method Effect on Clinical Outcomes (Time to Relapse) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on clinical outcomes as measured by time to relapse.
Effect on Health-related Quality of Life (Weight) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (weight) as measured by the change in patient's body weight in kilograms.
Effect on Clinical Outcomes (Treatment-related Mortality) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on clinical outcomes as measured by treatment-related mortality.
Effect on Clinical Outcomes (Incidence of Infection) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on clinical outcomes as measured by incidence of infection.
Effect on Health-related Quality of Life (Nutrition) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (nutrition) as measured by the Patient-Generated Subjective Global Assessment (PG-SGA), which gives 2 results: a numerical score between 0 and 16, where a higher score indicates higher nutritional risk, and a categorical score where A = well nourished, B = moderately malnourished, and C = severely malnourished.
Effect on Health-related Quality of Life (Social Support/Social Isolation) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (social support) as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Social Isolation assessment, which results in a numerical score between 6 and 30, with a higher score indicating a greater level of social participation.
Effect on Health-related Quality of Life (EuroQoL-5 Dimension-5 Level) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life as measured by the EuroQoL-5 Dimension-5 Level (EQ-5D-5L), which results in a 5-digit health state, where each digit is between 1 and 5 (e.g. 12345 or 11111). For each digit, a higher number indicates a greater severity of problems.
Effect on Clinical Outcomes (Incidence of Graft-versus-host disease) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on clinical outcomes as measured by incidence of graft versus host disease.
Length of Stay At day of hospital discharge The length of hospital stay measured in days from time of transplant to time of discharge.
Effect on Health-related Quality of Life (Mental Health/Depression Scale) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (mental health) as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression scale, which results in a numerical value between 8 and 40, with a higher number indicating greater severity of depression.
Effect on Health-related Quality of Life (Mental Health/Anxiety scale) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (mental health) as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale, which results in a numerical value between 7 and 35, with a higher number indicating greater severity of anxiety.
Effect on Health-related Quality of Life (Albumin Level) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (albumin level) as measured by the change in patient's albumin level in grams per deciliter; low serum albumin levels can predict higher cancer mortality.
Effect on Health-related Quality of Life (Social Support/Emotional Support) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (social support) as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Support assessment, which results in a numerical score between 8 and 40, with a higher score indicating a greater level of social participation.
Effect on Health-related Quality of Life (Return to Work) At Day 180 and Day 365 Effect on health-related quality of life as measured by assessing the patient's return to work as an indicator of recovery.
Effect on Clinical Outcomes (Overall Survival) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on clinical outcomes as measured by overall survival.
Effect on Health-related Quality of Life (Physical Activity/Short Physical Performance Battery) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (physical activity) as measured by performance on the Short Physical Performance Battery, which results in a score from 0 to 12 points, with a higher number indicating better physical performance.
Effect on Health-related Quality of Life (Physical Activity/30-Second Sit-to-Stand Test) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related qulaity of life (physical activity) as measured by the 30-second sit-to-stand test, which measures the number of times an individual can stand up from a chair and sit back down within 30 seconds, with a higher number indicating greater fitness.
Effect on Health-related Quality of Life (Physical Activity/Fried Frailty) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (physical activity) as measured by the Fried Frailty assessment, which results in a score from 0 to 5, with a higher number indicating greater frailty.
Effect on Health-related Quality of Life (Physical Activity/Fall Question) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (physical activity) as measured by the Fall Question, a structured questionnaire asking about any history of falls, with a higher number of falls indicating greater fall risk and physical vulnerability.
Effect on Health-related Quality of Life (Physical Activity/Physical Function Questionnaire) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (physical activity) as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function questionnaire, which results in a numerical score between 0 and 100, with a higher number indicating better physical function.
Effect on Health-related Quality of Life (Physical Activity/Fatigue Questionnaire) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (physical activity) as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire, which results in a numerical score between 0 and 100, with a higher number indicating greater symptom burden.
Effect on Health-related Quality of Life (Physical Activity/International Physical Activity Questionnaire) At Baseline Effect on health-related quality of life (physical activity) as measured by the International Physical Activity Questionnaire, which provides 2 results: a categorical rating of low, moderate, or high activity level, and a number of Metabolic Equivalent of Task (MET) minutes per week, with a higher number indicating a greater amount of physical activity.
Effect on Health-related Quality of Life (Cognitive/Montreal Cognitive Assessment) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (cognitive) as measured by the Montreal Cognitive Assessment (MOCA), which results in a numerical score between 0 and 30, with a higher number indicating better cognitive functioning.
Effect on Health-related Quality of Life (Mental Health/Lorig Self-Efficacy) At Baseline, Day -10, Day 30, Day 90, Day 180, and Day 365 Effect on health-related quality of life (mental health) as measured by the Lorig Self-Efficacy for Managing Chronic Disease Scale, which results in a numerical score between 1 and 10, with a higher number indicating higher self-efficacy.
Trial Locations
- Locations (3)
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
Duke University
🇺🇸Durham, North Carolina, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States