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Home-based Exercise in Renal Transplant Recipients (ECSERT)

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ClinicalTrials.gov Identifier: NCT04123951
Recruitment Status : Recruiting
First Posted : October 11, 2019
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
University of Leicester

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.

Condition or disease Intervention/treatment Phase
Kidney Transplant; Complications Other: Home-based Exercise Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : January 30, 2020
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Home-based Exercise
Patients in this arm will complete a 12 week home-based aerobic and resistance exercise training programme. There will be a 2 week period prior to this in which patients will complete up to 6 supervised sessions in order to learn about the home-based exercise training. There will be a 4 week return visit and an optional 8 week return visit in order to reassess fitness and aid the patients with any questions or queries they may have and to aid them in progressing their exercise.
Other: Home-based Exercise
Patients in the home-based exercise arm will complete a 12 week home-based aerobic and resistance exercise training programme. There will be a 2 week period prior to this in which patients will complete up to 6 supervised sessions in order to learn about the home-based exercise training. There will be a 4 week return visit and an optional 8 week return visit in order to reassess fitness and aid the patients with any questions or queries they may have and to aid them in progressing their exercise.

No Intervention: Control

In this arm patients will continue 'as normal' with daily activities.

Patients in this arm will be offered the exercise intervention once they have completed post 12 week assessments.




Primary Outcome Measures :
  1. Change in Left ventricular mass (g/m) [ Time Frame: Baseline and 12 weeks ]
    Measured using multi-parametric cardiac MRI (CMR)

  2. Change in left/right ventricular volumes (ml) [ Time Frame: Baseline and 12 weeks ]
    Measured using multi-parametric cardiac MRI (CMR)

  3. Change in ejection fractions (%) [ Time Frame: Baseline and 12 weeks ]
    Measured using multi-parametric cardiac MRI (CMR)

  4. Change in native and post-contrast T1 mapping time (ms) [ Time Frame: Baseline and 12 weeks ]
    Measured using multi-parametric cardiac MRI (CMR)

  5. Change in Myocardial systolic-strain (%) [ Time Frame: Baseline and 12 weeks ]
    Measured using multi-parametric cardiac MRI (CMR)

  6. Change in peak early-diastolic strain rate (%s-1) [ Time Frame: Baseline and 12 weeks ]
    Measured using multi-parametric cardiac MRI (CMR)

  7. Change in Aortic pulse wave velocity (m/s) [ Time Frame: Baseline and 12 weeks ]
    Measured using multi-parametric cardiac MRI (CMR)

  8. Change in aortic distensibility (mmHg-1×10-3) [ Time Frame: Baseline and 12 weeks ]
    Measured using multi-parametric cardiac MRI (CMR)

  9. Change in Myocardial and hepatic triglyceride content (%) [ Time Frame: Baseline and 12 weeks ]
    Measured using multi-parametric cardiac MRI (CMR)


Secondary Outcome Measures :
  1. Recruitment Rate [ Time Frame: Post 12 week intervention ]
    The feasibility of recruitment and interest of patients is an essential component of whether a full trial is feasible. The number of eligible patients and number of consented will be recorded. Monthly recruitment rate and the time taken to recruit 10 (25%), 20 (50%), 30 (75%), and 40 (100%) patients will be recorded.

  2. Number of participants lost to follow up [ Time Frame: Post 12 week intervention ]
    This is the number of participants leaving the trial due to being uncontactable

  3. Number of exercise sessions completed per week [ Time Frame: Post 12 week intervention ]
    This will assess adherence to the intervention

  4. Number of participants dropping out of the trial [ Time Frame: Post 12 week intervention ]
    Otherwise known as the attrition rate

  5. Number of adverse events [ Time Frame: Post 12 week intervention ]
    This is a measure of the trial safety

  6. Aerobic Capacity (change) [ Time Frame: Baseline, 2 weeks, 4 weeks and 12 weeks ]
    Measured by cardiopulmonary exercise test which produces V02 (maximal oxygen uptake) in both l/min and ml/kg/min. This is a measure of a participants aerobic capacity.

  7. Timed up and go test (TUAG)(change) [ Time Frame: Baseline and 12 weeks ]
    To determine fall risk and measure the progress of balance, sit to stand and walking. Patient sits and then the time taken to stand up and walk 3 meters and return is measured. If a patient took 14 seconds or longer he or she was classified as high-risk for falling

  8. Habitual Physical Activity (change) [ Time Frame: Baseline and 12 weeks ]
    Via accelerometry

  9. Lower limb strength (change) [ Time Frame: Baseline and 12 weeks ]
    Dynamometry

  10. Upper Limb Strength (change) [ Time Frame: Baseline and 12 weeks ]
    Hand grip

  11. Change in circulation markers of systemic inflammation [ Time Frame: Baseline and 12 weeks ]
    Blood Sampling including but not limited to IL-6, CRP, IL-10, TNF-Alpha

  12. Muscle quality using Ultrasound Imaging (change) [ Time Frame: Baseline and 12 weeks ]
    Cross-sectional area (cm2)

  13. Muscle quality using Ultrasound Imaging (change) [ Time Frame: Baseline and 12 weeks ]
    fat thickness (mm)

  14. Muscle Elasticity (change) [ Time Frame: Baseline and 12 weeks ]
    Muscle elasticity will be measures using a MyotonPro device

  15. Lower limb endurance (change) [ Time Frame: Baseline and 12 weeks ]
    Sit to stand 60 test measuring how many 'sit to stands' can be performed in 60 seconds

  16. Balance (change) [ Time Frame: Baseline and 12 weeks ]
    Measured using a 'wii-fit' style board. Better balance is an idicator of falls risk

  17. Gait speed (change) [ Time Frame: Baseline and 12 weeks ]
    Gait speed is measure as the time taken to walk 4 meters. Slower speeds have been linked to higher mortality risk

  18. Height [ Time Frame: Baseline ]
    Height measured in meters

  19. Weight (change) [ Time Frame: Baseline and 12 weeks ]
    Weight measured in kg

  20. Body fat % (change) [ Time Frame: Baseline and 12 weeks ]
    Body fat measured using bio electrical impedance analysis


Other Outcome Measures:
  1. Integrated Palliative care Outcome Scale for Renal (I-POS-Renal)(change) [ Time Frame: Baseline and 12 weeks ]
    IPOS-Renal is a short measure (11 questions), combining the most common symptoms renal patients experience plus additional items from IPOS on concerns beyond symptoms, such as information needs, practical issues, family anxiety. IPOS has been validated in a mixed population of those with cancer and non-cancer diagnosis, including renal patients, and shows good content and construct validity, reliability, and responsiveness to change. Each symptom is rated on a scale of 0-4 for how much that symptom effects the participant. 0 is not at all and 4 is severely. Higher total scores indicate more symptom burden.

  2. Short Form Health Survey (SF-12)(change) [ Time Frame: Baseline and 12 weeks ]
    Categorical questions that assess limitations in role functioning as a result of physical and emotional health. The survey also contains Likert response formats including those that are on a three-point scale (e.g., limited a lot, limited a little, or not limited at all) that assess limitations in physical activity and physical role functioning. A five-point scale (e.g., not at all, a little bit, moderately, quite a bit, and extremely) that assesses pain, and a five-point scale that assesses overall health (excellent, very good, good, fair, and poor) are included. The SF-12 also contains a six-point scale (e.g., all of the time, most of the time, a good bit of the time, some of the time, a little of the time, and none of the time) that assesses mental health, vitality, and social functioning. Two summary scores: mental health (MCS12), and physical health (PCS12). The scores are represented as t-scores that are linear transformations with a mean of 50 and a standard deviation of 10

  3. Patient Activation Measure (PAM)(Change) [ Time Frame: Baseline and 12 weeks ]

    Individuals are asked to complete a short survey and based on their responses, they receive a PAM score (between 0 and 100). The resulting score places the individual at one of four levels of activation, each of which reveals insight into a range of health-related characteristics, including behaviours and outcomes. The four levels of activation are:

    Level 1: Individuals tend to be passive and feel overwhelmed by managing their own health. They may not understand their role in the care process.

    Level 2: Individuals may lack the knowledge and confidence to manage their health.

    Level 3: Individuals appear to be taking action but may still lack the confidence and skill to support their behaviours.

    Level 4: Individuals have adopted many of the behaviours needed to support their health but may not be able to maintain them in the face of life stressors.

    Particulars of the scoring system (and scales) are not disclosed by the license holder


  4. (FACIT-F)(change) [ Time Frame: Baseline and 12 weeks ]
    The FACIT-fatigue scale is a 13-item patient-reported measure of fatigue with a 7-day recall period. Items are scored on a 0 - 4 response scale with anchors ranging from "Not at all" to "Very much so". To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue

  5. Pittsburgh Sleep Quality Index (PSQI)(change) [ Time Frame: Baseline and 12 weeks ]
    In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04123951


Contacts
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Contact: Matthew Graham-Brown 0116 258 4346 mgb23@le.ac.uk
Contact: Roseanne Billany 0116 258 4346 roseanne.billany@bath.edu

Locations
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United Kingdom
University Hospital Leicester NHS Trust Recruiting
Leicester, Leicestershire, United Kingdom, LE5 4PW
Contact: Matthew Graham-Brown         
Sponsors and Collaborators
University of Leicester
Investigators
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Principal Investigator: Matthew Graham-Brown University of Leicester
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Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT04123951    
Other Study ID Numbers: 0714
First Posted: October 11, 2019    Key Record Dates
Last Update Posted: March 11, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Leicester:
Kidney Transplant
Cardiovascular Disease
Home-based Exercise
Exercise