Multimodal Prehabilitation in Frail and Non-frail Patients Waiting for a Kidney Transplantation (the FRAILMAR Study)

Study Overview
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Brief Summary
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Frailty is very frequent among patients waiting for a kidney transplantation (KT). Frailty and poor fitness powerfully predict mortality, kidney graft survival, and healthcare utilization after KT. Frailty in patients with chronic kidney disease (CKD) displays a constellation of features that characterize a special population. Intervention is essential to improve quality of life for frail CKD patients, regardless of their age. A pre-transplant intervention including physical therapy, nutritional measures and psychological support scheduled for before the transplant may improve patient retention and compliance, better mitigate the effects of frailty and poor fitness after KT, and improve main outcomes in frail CKD patients. The main objective is to assess effectiveness, feasibility and safety of a prehabilitation program (exercise, nutritional plans, psychological advice) in frail and non-frail KT candidates on clinical and functional outcomes after KT.

Detailed Description
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Frailty is very frequent among patients with chronic kidney disease (CKD) included in the waiting list for deceased donor kidney transplantation (KT), and outcomes are worsened in those frail recipients after KT. Frailty and poor fitness powerfully predict mortality, kidney graft survival, and healthcareutilization after KT. Frailty in CKD patients displays a unique constellation of features such as muscle wasting, anorexia, protein energy wasting, inflammation, oxidative stress, catabolic/anabolic hormone imbalance, metabolic acidosis, and other cellularalterations that characterize a special population. Intervention is essential to improve quality of life for frail CKD patients, regardless of their age. Efforts to intervene with post- transplant physical therapy have been met with limited success, in large part due to high study dropout. A pre-transplant clinical framework for multimodal prehabilitation interventions including physicaltherapy, nutritional measures and psychological support scheduled for before the transplant may improve patient retention andcompliance, better mitigate the effects of frailty and poor fitness after KT, and improve main outcomes in frail CKD patients. The main objective of this study is to assess effectiveness, feasibility and safety of multimodal prehabilitation (exercise, nutritional plans, psychological advice) in frail and non-frail KT candidates in the context of a randomized controlled clinical trial. The primary endpoint will be a composite achievement of clinical and functional outcomes in frail and non-frail KT candidates after KT.

Official Title
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Frailty in Patients With Advanced Chronic Kidney Disease Waiting for a Kidney Transplantation. A Randomized Clinical Trial of Multimodal Prehabilitation.

Conditions
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Chronic Kidney Diseases

Intervention / Treatment
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* Other: Multimodal prehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults patients with chronic kidney disease Inclusion in the waiting list for deceased donor kidney transplantation in the period September 2020 to August 2022 Exclusion Criteria: Patients unable to perform the exercise plan or giving informed consent

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Clinical Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multimodal intervention<br>supervised physical training (1-hour sessions, 24 sessions, 8 weeks) + nutritional supplementation + psychological advice | Other: Multimodal prehabilitation<br>* Exercise + nutritional supplementation + psychological advice<br>|
| No Intervention: Standard Care<br>Healthy living recommendations | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bad-Outcome Composite Endpoint | Delayed draft function >14 days + never functioning kidney + non-elective readmission before day 90 + surgical complications (wound healing problems, obstructive lymphocele, vascular thrombosis, urinary stenosis or leak, acute hemorrhage, immediate re-intervention) + discharge to an assisted facility + all-cause death. | 90 days post-kidney transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in exercise capacity | Changes in peak oxygen uptake (higher scores mean better outcome) | Post-intervention (12 weeks) | 
| Changes in peripheral muscle strength | Changes in handgrip and quadriceps muscles strength (higher scores mean better outcome) | Post-intervention (12 weeks) | 
| Changes in respiratory muscle strength | Changes in maximal inspiratory and expiratory muscle strength (higher scores mean better outcome) | Post-intervention (12 weeks) | 
| Changes in physical activity | Changes in physical activity assessed by activity monitors (higher scores mean better outcome) | Post-intervention (12 weeks) | 
| Attendance | Attended sessions (0-100%, patients are expected to attend a minimum of 80% sessions) | Post-intervention (12 weeks) | 
| Exercise tolerability | Patients not requiring exercise discontinuation or intensity modification | Post-intervention (12 weeks) | 
| Changes in muscle mass | Changes in muscle mass assessed with total body dual energy X-ray | 1 month post-KT | 
| Changes in mood state | Changes in Hospital Anxiety Depression Scale | Through study completion, an average of 1 year | 
| Changes in health-related quality of life | Score in the Short-Form 36 questionnaire (8 dimensions scoring 0-100, higher scores mean better outcomes) | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic kidney disease, kidney transplantation, frailty, prehabilitation, exercise, nutritional status, psychological advice, sarcopenia