Clinical trial NCT04123951: Home-based Exercise in Renal Transplant Recipients
Official title: A Pilot Randomised Controlled Trial of the Effects of a Structured, Home-based Exercise Program on Cardiovascular StructurE and Function in Renal Transplant Recipients: The ECSERT Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Kidney Transplant; Complications
Keywords: Kidney Transplant
Cardiovascular Disease
Home-based Exercise
Exercise
Lead sponsor: University of Leicester
Sponsor class: OTHER
First posted: 2019-10-11
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Although patients who have received a kidney transplant have better health than patients on dialysis, heart problems are still the commonest cause of death for kidney transplant recipients. This is because diseases like high blood pressure and diabetes are more common in patients with kidney transplants as well as factors related to having kidney disease itself and the medications transplant recipients have to take to stop them rejecting their transplanted kidney. Exercise is known to help with heart disease in lots of conditions and improves many of the risk factors known to cause heart disease in kidney transplant recipients. This study will investigate whether an individualised, home-based, exercise program improves heart disease in kidney transplant recipients. The study is a randomised controlled trial, with half the patients completing the 12 week exercise programme and the other half continuing with their normal care. The investigators will use detailed MRI scans to assess patient's hearts and blood vessels at the start and end of the study. The investigators will also assess changes in physical function, exercise capacity, blood markers of heart disease, changes in body type and quality of life measures assessed with questionnaires.

Detailed description: Kidney transplantation confers a significant survival advantage over remaining on dialysis, but CVD remains the leading cause of death for RTRs and of graft loss. Acute myocardial infarction accounts for 15-20% of CVD-related deaths in RTRs, but sudden cardiac death, or death from fatal arrhythmia account for at least double this number, suggesting classical atheromatous coronary artery disease driven by traditional cardiometabolic risk factors, is not the dominant driving force of CVD in RTRs. Non-traditional cardiometabolic risk factors including endothelial dysfunction, systemic inflammation, acute rejection, anaemia and deranged bone-mineral metabolism are of at least equal importance in the pathogenesis of CVD in RTRs and drive pathological changes in cardiovascular structure and function that associate strongly with mortality. This is further illustrated by the fact that traditional CVD risk-stratification tools dramatically underestimate cardiovascular risk in patients with CKD, coronary revascularization does not improve outcomes for RTRs as it does in the general population and cardiac events are more likely to be fatal in RTRs than the general population. Immunosuppressive agents are well known to drive traditional CVD risk factors, but also drive non-traditional cardiometabolic risk factors. Cost-effective, deliverable interventions are needed to address the burden of CVD in RTRs by targeting traditional and non-traditional risk factors. Supervised exercise interventions in RTRs improve cardiorespiratory fitness and a variety of traditional and non-traditional risk factors for CVD, including metabolic profile, vascular stiffening, central adiposity and inflammatory cell and cytokine profiles, but are not realistically deliverable in the current financial climate. Home-based exercise training programs have been shown to be deliverable in patients on dialysis and patients undergoing cardiac rehabilitation, but the effectiveness and deliverability of home-based exercise interventions are largely untested in RTRs. It cannot be assumed such programs will be acceptable to RTRs, whose home-lives, social and occupational circumstances are significantly different to dialysis and cardiac patients. Many RTRs have had enforced sedentary lifestyles prior to transplantation as dialysis patients and their goals for rehabilitation as well as the disease processes at work are different to both dialysis and cardiac patients.

There are limited data on whether exercise-induced improvements in cardiometabolic risk translate into improvements in cardiovascular structure and function in RTRs. CMR is able to measure multiple clinically pertinent aspects of CVD processes in RTRs that relate closely to outcome with great accuracy, including:

* left ventricular hypertrophy
* myocardial fibrosis
* aortic stiffness
* coronary artery function
* myocardial steatosis
* subclinical systolic and diastolic dysfunction

This pilot randomised clinical trial will assess the deliverability of a combined aerobic and resistance, home-based, exercise intervention in RTRs. It will define recruitment and dropout rates from this newly designed, home-based, intervention and baseline values for CMR measures that assess prognostically important aspects of CVD in RTRs for the first time. Furthermore, it will test the effects of the intervention on traditional and novel CMR outcome measures that assess prognostically important aspects of CVD that relate directly to cardiovascular outcomes for the first time, providing estimates of effect-sizes on outcome measures. These data will be used to inform the design of a future, definitive study. This study will further the investigator's ability to make objective measures of cardiovascular health in RTRs, with the opportunity to compare CMR measures with traditional measures of cardiovascular fitness. The qualitative component of this study will refine the exercise intervention to maximize uptake in future studies and adoption into clinical practice.

Eligibility criteria: Inclusion Criteria:

* Age great than 18 years old
* Prevalent RTR longer than 1year
* Able and willing to give informed consent
* Increased cardiometabolic risk, with at least one of:

Diabetes mellitus Dyslipidaemia Hypertension History of ischaemic heart disease or cerebrovascular disease Obesity (BMI above 30)

Exclusion Criteria:

* Unable to undertake exercise due to physical or psychological barriers
* Unable to undergo CMR scanning (incompatible implants, claustrophobia, allergy to agents)
* Contraindication to exercise training (American College of Sports Medicine guidelines)
* Female participants who are pregnant, lactating, or planning pregnancy during the course of the study.
* Scheduled elective surgery or other procedures requiring general anaesthesia during the study.
* Any other significant disease or disorder (i.e. significant co-morbidity including unstable hypertension, potentially lethal arrhythmia, myocardial infarction within 6 months, unstable angina, active liver disease, uncontrolled diabetes mellitus (HbA1c greater than or equal to 9%), advanced cerebral or peripheral vascular disease) which, in the opinion of the patient's own clinician the Principle Investigator may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
* Inability to give informed consent or comply with testing and training protocol for any reason.

Primary outcomes:
measure: Change in Left ventricular mass (g/m)
timeFrame: Baseline and 12 weeks
measure: Change in left/right ventricular volumes (ml)
timeFrame: Baseline and 12 weeks
measure: Change in ejection fractions (%)
timeFrame: Baseline and 12 weeks
measure: Change in native and post-contrast T1 mapping time (ms)
timeFrame: Baseline and 12 weeks
measure: Change in Myocardial systolic-strain (%)
timeFrame: Baseline and 12 weeks
measure: Change in peak early-diastolic strain rate (%s-1)
timeFrame: Baseline and 12 weeks
measure: Change in Aortic pulse wave velocity (m/s)
timeFrame: Baseline and 12 weeks
measure: Change in aortic distensibility (mmHg-1×10-3)
timeFrame: Baseline and 12 weeks
measure: Change in Myocardial and hepatic triglyceride content (%)
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Recruitment Rate
timeFrame: Post 12 week intervention
measure: Number of participants lost to follow up
timeFrame: Post 12 week intervention
measure: Number of exercise sessions completed per week
timeFrame: Post 12 week intervention
measure: Number of participants dropping out of the trial
timeFrame: Post 12 week intervention
measure: Number of adverse events
timeFrame: Post 12 week intervention
measure: Aerobic Capacity (change)
timeFrame: Baseline, 2 weeks, 4 weeks and 12 weeks
measure: Timed up and go test (TUAG)(change)
timeFrame: Baseline and 12 weeks
measure: Habitual Physical Activity (change)
timeFrame: Baseline and 12 weeks
measure: Lower limb strength (change)
timeFrame: Baseline and 12 weeks
measure: Upper Limb Strength (change)
timeFrame: Baseline and 12 weeks
measure: Change in circulation markers of systemic inflammation
timeFrame: Baseline and 12 weeks
measure: Muscle quality using Ultrasound Imaging (change)
timeFrame: Baseline and 12 weeks
measure: Muscle quality using Ultrasound Imaging (change)
timeFrame: Baseline and 12 weeks
measure: Muscle Elasticity (change)
timeFrame: Baseline and 12 weeks
measure: Lower limb endurance (change)
timeFrame: Baseline and 12 weeks
measure: Balance (change)
timeFrame: Baseline and 12 weeks
measure: Gait speed (change)
timeFrame: Baseline and 12 weeks
measure: Height
timeFrame: Baseline
measure: Weight (change)
timeFrame: Baseline and 12 weeks
measure: Body fat % (change)
timeFrame: Baseline and 12 weeks
Other outcomes:
measure: Integrated Palliative care Outcome Scale for Renal (I-POS-Renal)(change)
timeFrame: Baseline and 12 weeks
measure: Short Form Health Survey (SF-12)(change)
timeFrame: Baseline and 12 weeks
measure: Patient Activation Measure (PAM)(Change)
timeFrame: Baseline and 12 weeks
measure: (FACIT-F)(change)
timeFrame: Baseline and 12 weeks
measure: Pittsburgh Sleep Quality Index (PSQI)(change)
timeFrame: Baseline and 12 weeks
Locations:
city: Leicester
country: United Kingdom
facility: University Hospital Leicester NHS Trust
state: Leicestershire
Study officials:
affiliation: University of Leicester
name: Matthew Graham-Brown
role: PRINCIPAL_INVESTIGATOR
References:
citation: Billany RE, Vadaszy N, Bishop NC, Wilkinson TJ, Adenwalla SF, Robinson KA, Croker K, Brady EM, Wormleighton JV, Parke KS, Cooper NJ, Webster AC, Barratt J, McCann GP, Burton JO, Smith AC, Graham-Brown MP. A pilot randomised controlled trial of a structured, home-based exercise programme on cardiovascular structure and function in kidney transplant recipients: the ECSERT study design and methods. BMJ Open. 2021 Oct 5;11(10):e046945. doi: 10.1136/bmjopen-2020-046945.