Molecular and Clinical Response to a Single Bout of Aerobic Exercise in a Multimorbid Population: a Study From the Consortium on Precision EXercise in Aging

Study Overview
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Brief Summary
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The combination of data from different origins (biological, health, patient-related) has the potential to improve care for the elderly. Precision approaches that are emerging in health are based on the premise that a better understanding of the biological responses to interventions will make it possible to optimize the treatments. In the field of exercise, this type of approach is emerging. This pilot study aims to collect preliminary data to demonstrate that a patient-centric vision with data from multiple sources is mandatory to personalize exercise intervention and improve health care. Older adults with end-stage chronic disease treated by hemodialysis represent a population of choice that requires personalized care since they are multimorbid and exhibit a complex health profile. On the other hand, the beneficial effects of exercise are still little understood and the avoidance of adverse effects in response to exercise such as hypotension during dialysis remains uninvestigated.Objective: Demonstrate the feasibility of an integrative approach by combining omics, clinical data, patient-related outcomes (PRO) as well as exercise variables (e.g., intensity, duration) Methods: A total of 10 people aged 60 and over will be recruited to randomly perform 2 experimental conditions: hemodialysis alone (CONT) or hemodialysis + aerobic exercise (EX), which will be carried out over 2 visits one week apart. These visits will take place at the scheduled time of the hemodialysis treatment. The variables of interest are: blood pressure response to a single bout of exercise exercise (during and post-exercise), symptoms (with visual analogue scales within 36 hours of the visit + Dialysis symptom index for the 7 days after the experimental visit), dialysis efficiency (Kt/V) and biological response (proteomics and metabolomics). Health-related quality of life (KDQOL questionnaire), medical data (electronic medical record), and level of physical activity (PASE questionnaire and smart watch; Apple Watch) will be evaluated.

Official Title
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Integration of Multi-omics, Health Profile, Patient-related Outcomes and Exercise Data to Improve and Personalize Health Care in Hospital Settings: A CPExA Proof of Concept

Conditions
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Multimorbidity - End-stage Kidney Disease

Intervention / Treatment
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* Other: Aerobic exercise
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: being treated by hemodialysis for end-stage kidney disease for at least 3 months medically eligible Exclusion Criteria: diagnosed neurocognitive decline hip fracture with recent hemiarthroplasty preventing hip flexion while pedalling, COVID-19 positive, already included in another study.

Ages Eligible for Study
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Minimum Age: 60 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: Crossover Assignment
Interventional Model Description: Each participant performed 2 experimental conditions (rest, moderate continuous aerobic exercise with our cycle ergometer prototype - EXALT).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic intradialytic exercise<br>10 patients will perform Aerobic exercise with the cycle ergometer prototype (EXALT) during hemodialysis | Other: Aerobic exercise<br>* EX: 30 min of aerobic exercise (3/10 Borg scale) during hemodialysis treatment (between 30 min and 3h of treatment).<br>|
| Experimental: Standard care<br>10 patients will receive hemodialysis treatment (usual care) | Other: Control<br>* CONT: participants will receive hemodialysis treatment only (usual care)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure | Measured using standard clinical procedures (Automatic Blood Pressure Monitor at rest and with aneroid sphygmomanometer during and after exercise) | Before and after the condition as well as every 5 minutes during the 20 minutes after (10 measurements). After this time frame, each 30 minutes up to the end of the dialysis session. | 
| Change in perceived fatigue | 10-centimeter horizontal visual analog scale, going from no fatigue (left) to extreme fatigue (right) | Measured at 2:00 pm and 6:00 pm the day of the experimental condition and at 10:00 am, 2:00 pm and 6:00 pm the day following the experimental condition (for a total of 24 hours). | 
| Change in perceived sleepiness | 10-centimeter horizontal visual analog scale, going from no sleepiness (left) to extreme sleepiness (right) | Measured at 2:00 pm and 6:00 pm the day of the experimental condition and at 10:00 am, 2:00 pm and 6:00 pm the day following the experimental condition (for a total of 24 hours). | 
| Change in mood | 10-centimeter horizontal visual analog scale, going from very bad (left) to very good (right) | Measured at 2:00 pm and 6:00 pm the day of the experimental condition and at 10:00 am, 2:00 pm and 6:00 pm the day following the experimental condition (for a total of 24 hours). | 
| Change in perceived soreness | 10-centimeter horizontal visual analog scale, going from no soreness (left) to extreme soreness (right) | Measured at 2:00 pm and 6:00 pm the day of the experimental condition and at 10:00 am, 2:00 pm and 6:00 pm the day following the experimental condition (for a total of 24 hours). | 
| Change in perceived sleep quality | 10-centimeter horizontal visual analog scale, going from very bad (left) to extreme soreness (right) | Measured at 10:00 am the day following the experimental condition. | 
| Plasma Metabolome and proteome at the end of the experimental (exercise) condition | A blood draw will be realized immediately at the end of the dialysis session comprising the exercise condition. The plasma metabolome and proteome will be determined using mass spectrometry. | After 30 minutes of exercise | 
| Plasma Metabolome and proteome at the end of the control (rest) condition | A blood draw will be realized immediately at the end of the dialysis session representing the control condition. The plasma metabolome and proteome will be determined using mass spectrometry. | After 30 minutes of rest | 
| Single pool Kt/V, experimental (exercise) condition | measured using standard clinical procedures (blood draw before and at the end of the dialysis session comprising the exercise condition, by a research nurse). | After 4 hours of dialysis | 
| Single pool Kt/V, control (rest) condition | measured using standard clinical procedures (blood draw before and at the end of the dialysis session representing the condition, by a research nurse). | After 4 hours of dialysis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematocrit (%) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Hemoglobin (g/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Red blood cells count (10^12/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| White blood cells count (10^9/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Platelets count (10^9/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Red blood cell mean corpuscular hemoglobin (pg) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Red blood cell mean corpuscular volume (fL) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Red blood cell distribution width (%) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Plasma sodium (mmol/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Plasma potassium (mmol/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Plasma calcium (mmol/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Plasma phosphate (mmol/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Plasma glucose (mmol/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Plasma creatinine (mmol/L) | Routinely measured (monthly) as standard clinical practice, before a dialysis session. | Extracted from each patient's medical record at inclusion. | 
| Health-Related Quality of Life | French version of the Kidney Disease Quality of Life 36 items version 1.3 (KDQOL-36) | Once, at the beginning of the dialysis session comprising the first condition | 
| Disease-related symptoms | The French version of the Dialysis Symptom Index, consisting in a seven-day recall questionnaire assessing the presence and intensity of 30 symptoms | Twice, seven days after each experimental conditions | 
| Physical activity scale for the Elderly (PASE) questionnaire | Recall questionnaire of the previous week's leisure, occupational and domestic physical activity habits validated in older adults. | Once, at the beginning of the dialysis session comprising the first condition | 
| Estimated daily energy expenditure | Wrist-worn accelerometer (Apple Watch) | The watch will be worn during the 24 hours following each experimental condition |