Survivorship Post-HCT Optimization Program

Study Overview
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Brief Summary
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The purpose of this project is to investigate the effects of 12 weeks of high-intensity interval training (HIIT) and resistance training on several domains of health including physical function, cognitive function, mental health, and quality of life in patients who have undergone hematopoietic stem cell transplant (HCT). In addition, the project will determine the effects of 12 weeks of HIIT and resistance training on physical function, caregiver strain, mental health, and caregiver confidence in individuals who are providing care for patients undergoing HCT.

Official Title
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The Effect of High-intensity Interval Training (HIIT) and Resistance Training on Function, Health, and Quality of Life Outcomes Following Hematopoietic Stem Cell Transplant

Conditions
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Hematologic Malignancy

Intervention / Treatment
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* Behavioral: Exercise training


Participation Criteria
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Eligibility Criteria
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Patient Inclusion Criteria: ≥18 years old English speaking Within 90 ± 30 days post allogenic HCT Caregiver Inclusion Criteria: ≥18 years old English speaking Providing post-discharge care for the patient who has undergone HCT Patient and Caregiver Exclusion Criteria: Have an absolute contraindication to exercise including a recent acute cardiac event (<6 months), unstable angina, uncontrolled dysthymias causing symptoms or hemodynamic compromise, symptomatic aortic stenosis, uncontrolled symptomatic heart failure, acute pulmonary embolus, acute myocarditis or pericarditis, suspects or known dissecting aneurism, or coronary artery disease. In addition to these absolute contraindications, the patient and caregiver will complete cardiopulmonary exercise testing (CPET) where the heart rate and heart rhythm will be monitored via a 12-lead ECG before, during, and after the test. The results from the CPET will be reviewed by a physician before the subject is cleared to participate in the HIIT and resistance training program. If the participant is not cleared by the physician following the CPET, then the patient and his or her caregiver will not be eligible to participate in the study.

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: Supportive Care
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patient<br>These are patients who are 90 (±30) days post-allogeneic hematopoietic stem cell transplant. Patients will complete 12 weeks of exercise training. Patients will also complete assessments to evaluate physical function, cognitive function, mental health, social support, nutrition and diet, symptoms, quality of life, and financial status. They will use devices to capture activity data and vital signs. They will collect bio-specimens to assess microbiota and biomarkers. | Behavioral: Exercise training<br>* 12 weeks of high intensity interval training (HIIT) (3x/week) and resistance training (2x/week)<br>|
| Experimental: Caregiver<br>These are the assigned caregivers for the transplant patients. Caregivers will complete 12 weeks of exercise training. Caregivers will also complete assessments to evaluate physical function, caregiver support, and physical activity and exercise. They will collect bio-specimens to assess microbiota. | Behavioral: Exercise training<br>* 12 weeks of high intensity interval training (HIIT) (3x/week) and resistance training (2x/week)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to prescribed exercise program, as measured by number of total sessions completed |  | 12 weeks | 
| Compliance to prescribed HIIT sessions, as measured by total session time (in minutes) |  | 12 weeks | 
| Compliance to prescribed HIIT sessions, as measured by number of intervals completed |  | 12 weeks | 
| Compliance to prescribed HIIT sessions, as measured by number/percentage of intervals meeting target heart rates |  | 12 weeks | 
| Compliance to prescribed resistance sessions, as measured by number of sets completed |  | 12 weeks | 
| Compliance to prescribed resistance sessions, as measured by number of repetitions completed |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in physical function/activity, as measured by SPPB | All the task points are added which make the SPPB score. The cut-point for the SPPB is a score of 10. The cumulative and sections scores are assessed individually and comprehensively. This assessment score will be used as a tool for evaluating lower extremity functioning in older persons. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by 6-minute walk test | The baseline for each patient is made through an algorithm that factors the patients age and gender. The patient's score is compared to what a person that is the patient's same age and gender would get. This comparison is then used as a tool to assess aerobic capacity or endurance. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by 30-second sit-to-stand | Subjects will sit in a chair with their arms crossed over their chest and rise to a standing position, then return to seated position. They will repeat this as many times as they can in 30 seconds. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by grip strength | The hand grip is an indicator of upper body strength and has been found to be a good predictor of future functional limitations and disabilities. The hand grip score is determined based on how quickly the participant can squeeze the hand dynamometer. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by Fried Frailty | The scores of all of the sections are added and if the patient has a score greater or equal to three this assessment deems that the patients is frail. If the patient has a score between 1-2 the patient is deemed pre-frail. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by PROMIS Physical Function | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by bioelectrical impedance (BIA) | Participants will have body composition assessed by bioelectrical impedance spectroscopy (BIS) via a bioimpedance analysis (BIA) device. BIA equipment does not measure muscle mass directly, but instead derives an estimate of muscle mass based on whole-body electrical conductivity. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by CPET | Exercise capacity will be assessed using a symptom-limited Cardiopulmonary Exercise Test (CPET) on a cycle ergometer or for a six-minute step test with expired gas analysis to determine VO2peak, according to guidelines for clinical populations (Jones et al., 2012). All CPET data will be recorded as the highest 30-second value elicited during the CPET. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by Intramuscular Adipose Tissue (IMAT) | Longitudinal and transverse ultrasound images of the m. rectus femoris, vastus lateralis, m. intercostalis / m. pectoralis, (head) m. temporalis, and/or (head) styloglossus. Complex grayscale analysis of the images is used to calculate the IMAT. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by Intramuscular Glycogen Content (IMGC) | Longitudinal and transverse ultrasound images of the m. rectus femoris, vastus lateralis, m. intercostalis / m. pectoralis, (head) m. temporalis, and/or (head) styloglossus. Complex grayscale analysis of the images is used to calculate the IMGC. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by muscle thickness | Longitudinal and transverse ultrasound images of the m. rectus femoris, vastus lateralis, m. intercostalis / m. pectoralis, (head) m. temporalis, and/or (head) styloglossus, using greyscale analyses. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by muscle area | Longitudinal and transverse ultrasound images of the m. rectus femoris, vastus lateralis, m. intercostalis / m. pectoralis, (head) m. temporalis, and/or (head) styloglossus, using greyscale analyses. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in physical function/activity, as measured by subcutaneous fat layer thickness | Longitudinal and transverse ultrasound images of the m. rectus femoris, vastus lateralis, m. intercostalis / m. pectoralis, (head) m. temporalis, and/or (head) styloglossus, using greyscale analyses. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in cognitive function, as measured by Montreal Cognitive Assessment (MOCA) | This administered assessment is subdivided into visuospatial/executive (5pts), naming (3pts), memory (no points), attention(5pts), language(3pts), abstraction(2pts), delayed recall(5pts), and orientation(6pts). All the subdivided sections have as many questions as they have points. For analysis, the cut point is if the patient has less than 26 points. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in cognitive function, as measured by PROMIS Cognitive Function | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in cognitive function, as measured by RBANS | RBANS evaluation produces five index scores as well as a total summary score, and total scaled score. Scores range from 40 to 160, with higher scores indicating better performance (Smith et al., 2014). The scaled score classifies neuropsychological performance as: extremely low (69 and below), borderline (70-79), low average (80-89), average (90-109), high average (110-119), superior (120-129), and very superior (130 and above) (Batty et al., 2016; Randolph et al., 1998). | Baseline, Post-intervention (week 12), 1 Year | 
| Change in cognitive function, as measured by Trail making test | Trail Making Test parts A and B (TMT-A and -B) will be used for identification of cognitively impairment. Total time to completion will be used as outcome variable for both parts (ranging from 0 to 300 seconds, with higher scores indicating worse performance (Smith et al., 2014). An adjusted mean T-score also will be calculated ranging from 0 to 100 (mean score 50, higher score indicating better performance). The T-score can be adjusted for age, sex, education and ethnicity. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in cognitive function, as measured by Brief Cope | Scores are presented for three overarching coping styles as average scores (sum of item scores divided by number of items), indicating the degree to which the respondent has been engaging in that coping style. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in mental health, as measured by PHQ-9 | The PHQ-9 consists of 9 items, each of which is scored 0 to 3, giving a 0 to 27 severity score | Baseline, Post-intervention (week 12), 1 Year | 
| Change in mental health, as measured by PC-PTSD/PCL-5 | PC-PTSD is a 5 item screen to identify patients with probable PTSD. If the patient screens positive, they then take the PCL-5. The PCL-5 is a 20 item screen to assess symptoms of PTSD. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in mental health, as measured by PROMIS Depression | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in mental health, as measured by PROMIS Anxiety | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in diet/nutrition, as measured by Perioperative Nutrition Screen (PONS) | PONS analyzes BMI, weight loss, and food intake to screen for preoperative nutrition risk | Baseline, Post-intervention (week 12), 1 Year | 
| Change in diet/nutrition, as measured by PG-SGA/Clinician SGA | Scores for each section can range from 0-4 depending on severity and nutritional impact. The sum of all scores provides the Total PG-SGA score, which can be used to indicate the need for intervention (Bauer et al., 2002) | Baseline, Post-intervention (week 12), 1 Year | 
| Change in diet/nutrition, as measured by ASA-24 | ASA-24 is a self-administered 24-hour diet recall | Baseline, Post-intervention (week 12), 1 Year | 
| Change in diet/nutrition, as measured by Food Security | Participants will be given the USDA food security survey to review their food securities or insecurities. This is a 10 item survey. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in social support, as measured by PROMIS Emotional Support | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in social support, as measured by PROMIS Social Isolation | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in social support, as measured by Lorig Self Efficacy | The Self-Efficacy to Manage Chronic Disease Scale is made up of 6-items on a visual analog scale, ranging from 1 (not at all confident) to 10 (totally confident). | Baseline, Post-intervention (week 12), 1 Year | 
| Change in social support, as measured by CFC-14 | CFC-14 is a 14 item questionnaire to assess a patient's consideration of immediate and consideration of future consequences | Baseline, Post-intervention (week 12), 1 Year | 
| Change in social support, as measured by Brief Resilience Scale | BRS assesses the patient's ability to recover from stress. The possible score range on the BRS is from 1 (low resilience) to 5 (high resilience). | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by Caregiver Strain index | Tool to assess strain on long-term caregivers | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by Preparedness for Caregiving assessment | Items are scored by calculating the mean of all items with a range of 0-4. The higher the score, the more prepared the caregiver feels to give care. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by FACT-GP | 21 item assessment scored on a 5-point Likert scale | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by PHQ-2 | The PHQ-9 consists of 2 items, each of which is scored 0 to 3, giving a 0 to 6 severity score | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by PCL-5 | The PCL-5 is a 20 item screen to assess symptoms of PTSD. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by Ego Resiliency | 14 item survey scored from 0-56, where a higher score indicates higher level of resiliency | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by PROMIS Depression | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by PROMIS Anxiety | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by PROMIS Emotional Support | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in caregiver support, as measured by PROMIS Social Isolation | The questions are asked as interval format with 0-Never through 5-Always. Each of the PRO instruments will be scored on the T-score metric, where 50 is the mean of a reference population and 10 is the standard deviation of that population. | Baseline, Post-intervention (week 12), 1 Year | 
| Change in microbiota diversity, as measured by skin swabs | Skin swab samples batch sequenced and microbiome analyzed | Baseline, Post-intervention (week 12), 1 Year | 
| Change in microbiota diversity, as measured by stool samples | Changes in stool samples as measured by 16s rRNA sequencing | Baseline, Post-intervention (week 12), 1 Year | 
| Change in biomarkers of inflammation and frailty, as measured by blood plasma samples | Assays evaluating angiogenic, stromal, and inflammatory markers and markers of aging (the Pepper Panel) are used to assess inflammation and frailty | Baseline, Post-intervention (week 12), 1 Year | 
| Overall survival, as measured by medical record review |  | 1 year | 
| Disease-free survival, as measured by medical record review |  | 1 year | 
| Rate of bacterial infection, as measured by medical record review |  | 1 year | 
| Rate of fungal infection, as measured by medical record review |  | 1 year | 
| Rate of viral infection, as measured by medical record review |  | 1 year | 
| Rate of overall infection, as measured by medical record review |  | 1 year | 
| Rate of hospital admission, as measured by medical record review |  | 1 year | 
| Rate of intensive care unit admission, as measured by medical record review |  | 1 year | 
| Hospital length of stay, as measured by medical record review |  | 1 year | 
| Intensive care unit length of stay, as measured by medical record review |  | 1 year | 
| Number of patients with grade 2+ graft-versus-host disease, as measured by medical record review |  | 1 year | 
| Transplant length of stay (in days), as measured by medical record review |  | 1 year | 
| Number of patients who returned to work, as assessed by Work Assessment |  | 1 year | 
| Number of falls, as assessed by Falls questionnaire | Participants will answer Yes/No to whether they have had any falls in the preceding 6 months | 1 year | 
| Number of subjects who experienced delirium, as assessed by DOS assessment | The Delirium Observation Screening Scale is a 13-item observational scale of verbal and nonverbal behavior. The observations can be done during regular care. The DOS is used to optimize recognition of delirium. | 1 year | 
| Change in quality of life, as assessed by FACT-BMT assessment | 50 item assessment. Higher total and domain scores indicate greater quality of life. | Baseline, Post-intervention (12 weeks), 1 Year | 
| Change in quality of life, as assessed by EQ-5D-5L assessment | The 5D represents 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Five levels of severity are measured, as indicated by the 5L, ranging from no problems to extreme problems. All scores are converted into a summary index. | Baseline, Post-intervention (12 weeks), 1 Year | 
| Change in quality of life, as assessed by OARS IADL assessment | OARS IADL is a 7 item assessment that asks what level of assistance is needed to do 7 different activities of daily living | Baseline, Post-intervention (12 weeks), 1 Year |