Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of a Reduction in Renal Function on Cardiovascular Structure and Function (CRIB-DONOR II)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02973607
Recruitment Status : Recruiting
First Posted : November 25, 2016
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
Anna Price, University Hospital Birmingham NHS Foundation Trust

Tracking Information
First Submitted Date November 22, 2016
First Posted Date November 25, 2016
Last Update Posted Date October 12, 2018
Actual Study Start Date May 23, 2017
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 23, 2016)
Left ventricular mass and interstitial fibrosis [ Time Frame: 3 years ]
Measured by CMR (part 1 of study).
Original Primary Outcome Measures
 (submitted: November 22, 2016)
  • Left ventricular mass [ Time Frame: 3 years ]
    Measured by CMR (part 1 of study).
  • Left ventricular interstitial fibrosis [ Time Frame: 3 years ]
    Measured by CMR (part 1 of study).
Change History Complete list of historical versions of study NCT02973607 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: November 22, 2016)
  • Aortic compliance [ Time Frame: 3 years ]
    Measured by CMR (part 1 of study).
  • Cardiovascular age [ Time Frame: 3 years ]
    Measured by telomere length and studies of DNA damage (part 1 and 2 of study).
  • Oxidative stress, inflammation and collagen turnover [ Time Frame: 3 years ]
    Measured by assay and bioassay (part 1 of study).
  • Blood pressure [ Time Frame: 3 years ]
    Measured by ambulatory blood pressure monitoring (part 1 of study).
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Effects of a Reduction in Renal Function on Cardiovascular Structure and Function
Official Title Effects of a Reduction in Renal Function on Cardiovascular Structure and Function: A 5 Year Study of Kidney Donors.
Brief Summary

Chronic kidney disease (CKD) is present in 1 in 7 of the population and confers a high risk of cardiovascular disease. The pathophysiology of cardiovascular disease in CKD is poorly understood because CKD is always accompanied by confounding factors including the underlying disease process (e.g. diabetes mellitus, systemic vasculitis) and the consequences of CKD including hypertension, anaemia and inflammation.

Nephrectomy in kidney donors causes a 30% reduction in renal function providing an ideal study population to measure prospectively the effects of reduced kidney function on the cardiovascular system.

The CRIB-Donor study (ClinicalTrials.gov Identifier:NCT01028703) demonstrated adverse effects on cardiovascular structure and function at 12 months compared to controls including an increase in left ventricular mass. This proposal will measure the changes in cardiovascular structure and function, cardiovascular age and biochemical changes at 5 years providing information on the long term effects of reduced renal function.

Detailed Description

A reduction in renal function at one year in kidney donors is associated with adverse cardiovascular structural and functional changes. Increases in LV mass and perhaps fibrosis along with increased arterial stiffness are associated with adverse changes in prognostic imaging biomarkers and may in the long term contribute to the development of clinical disease such as heart failure and arrhythmia.

It is important to follow this valuable and well characterised cohort of subjects to investigate the further natural history of these cardiovascular effects and determine whether such changes tend to regress, stabilise or worsen over time.

Hypotheses:

The reduction in GFR occurring after surgical uni-nephrectomy in donors is associated with long term adverse cardiac and vascular effects which include:

  1. A sustained increased in left ventricular mass, impaired left ventricular systolic and diastolic function and increased left ventricular interstitial fibrosis.
  2. Reduced aortic distensibility.
  3. Increased systolic but not diastolic blood pressure.
  4. Increases in oxidative stress, inflammation and collagen turnover
  5. Cardiovascular ageing as evidenced by adverse effects on telomere length and DNA damage.

Study design:

We aim to follow up all 124 patients who originally took part in the CRIB-DONOR study at 5 years and eventually 10 years post nephrectomy.

Statistics and sample size:

Using the effect sizes and variances from our previous work (change in LV mass 7g, SD of change 10g) we calculate that by studying 50 subjects in each group we will have 93% power to detect a difference in LV mass of 7g with an alpha value of 0.05. Due to the nature of a follow up study some drop out can be expected. A minimum of 34 patients is required in each group in order to achieve an 80% power. This effect is clinically important; a fall in LV mass index of one SD has been shown to be associated with a 38% reduction in cardiovascular mortality.

With respect to telomere shortening, assuming mean and SD of base pair length of 5500 and 530 the study will be able to detect a difference of 0.612 SD, i.e. 324 base pairs. A sample size of 50 patients per group would provide a 85% power to detect a difference.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Serum, plasma, acellular urine and DNA (for telomere length).
Sampling Method Non-Probability Sample
Study Population Living donors and healthy controls
Condition
  • Chronic Kidney Disease
  • Hypertrophy, Left Ventricular
  • Hypertension
Intervention Procedure: Nephrectomy
This is observational in design.
Study Groups/Cohorts
  • Donors
    Patients who donated a kidney and took part in the original CRIB-DONOR study.
    Intervention: Procedure: Nephrectomy
  • Controls
    Healthy subjects who took part in the original CRIB-DONOR study.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: November 30, 2016)
124
Original Estimated Enrollment
 (submitted: November 22, 2016)
244
Estimated Study Completion Date July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

All patients who took part in the original CRIB-Donor study.

Exclusion Criteria:

Pregnant women

Patients will have previously met nationally set criteria for living donation which excludes those with:

Diabetes mellitus Atrial fibrillation Left ventricular dysfunction (ejection fraction <40% on transthoracic echocardiography) History of cardiovascular or pulmonary disease Evidence of hypertensive end-organ damage.

Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Dr Anna Price, MbChB 0121 371 4624 anna.price@uhb.nhs.uk
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT02973607
Other Study ID Numbers RRK5913
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Anna Price, University Hospital Birmingham NHS Foundation Trust
Study Sponsor University Hospital Birmingham NHS Foundation Trust
Collaborators Not Provided
Investigators
Principal Investigator: Professor John Townend, MbChB University Hospital Birmingham NHS Foundation Trust
PRS Account University Hospital Birmingham NHS Foundation Trust
Verification Date October 2018