<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02973607</url>
  </required_header>
  <id_info>
    <org_study_id>RRK5913</org_study_id>
    <nct_id>NCT02973607</nct_id>
  </id_info>
  <brief_title>Effects of a Reduction in Renal Function on Cardiovascular Structure and Function</brief_title>
  <acronym>CRIB-DONOR II</acronym>
  <official_title>Effects of a Reduction in Renal Function on Cardiovascular Structure and Function: A 5 Year Study of Kidney Donors.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Birmingham NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Birmingham NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic kidney disease (CKD) is present in 1 in 7 of the population and confers a high risk&#xD;
      of cardiovascular disease. The pathophysiology of cardiovascular disease in CKD is poorly&#xD;
      understood because CKD is always accompanied by confounding factors including the underlying&#xD;
      disease process (e.g. diabetes mellitus, systemic vasculitis) and the consequences of CKD&#xD;
      including hypertension, anaemia and inflammation.&#xD;
&#xD;
      Nephrectomy in kidney donors causes a 30% reduction in renal function providing an ideal&#xD;
      study population to measure prospectively the effects of reduced kidney function on the&#xD;
      cardiovascular system.&#xD;
&#xD;
      The CRIB-Donor study (ClinicalTrials.gov Identifier:NCT01028703) demonstrated adverse effects&#xD;
      on cardiovascular structure and function at 12 months compared to controls including an&#xD;
      increase in left ventricular mass. This proposal will measure the changes in cardiovascular&#xD;
      structure and function, cardiovascular age and biochemical changes at 5 years providing&#xD;
      information on the long term effects of reduced renal function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A reduction in renal function at one year in kidney donors is associated with adverse&#xD;
      cardiovascular structural and functional changes. Increases in LV mass and perhaps fibrosis&#xD;
      along with increased arterial stiffness are associated with adverse changes in prognostic&#xD;
      imaging biomarkers and may in the long term contribute to the development of clinical disease&#xD;
      such as heart failure and arrhythmia.&#xD;
&#xD;
      It is important to follow this valuable and well characterised cohort of subjects to&#xD;
      investigate the further natural history of these cardiovascular effects and determine whether&#xD;
      such changes tend to regress, stabilise or worsen over time.&#xD;
&#xD;
      Hypotheses:&#xD;
&#xD;
      The reduction in GFR occurring after surgical uni-nephrectomy in donors is associated with&#xD;
      long term adverse cardiac and vascular effects which include:&#xD;
&#xD;
        1. A sustained increased in left ventricular mass, impaired left ventricular systolic and&#xD;
           diastolic function and increased left ventricular interstitial fibrosis.&#xD;
&#xD;
        2. Reduced aortic distensibility.&#xD;
&#xD;
        3. Increased systolic but not diastolic blood pressure.&#xD;
&#xD;
        4. Increases in oxidative stress, inflammation and collagen turnover&#xD;
&#xD;
        5. Cardiovascular ageing as evidenced by adverse effects on telomere length and DNA damage.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      We aim to follow up all 124 patients who originally took part in the CRIB-DONOR study at 5&#xD;
      years and eventually 10 years post nephrectomy.&#xD;
&#xD;
      Statistics and sample size:&#xD;
&#xD;
      Using the effect sizes and variances from our previous work (change in LV mass 7g, SD of&#xD;
      change 10g) we calculate that by studying 50 subjects in each group we will have 93% power to&#xD;
      detect a difference in LV mass of 7g with an alpha value of 0.05. Due to the nature of a&#xD;
      follow up study some drop out can be expected. A minimum of 34 patients is required in each&#xD;
      group in order to achieve an 80% power. This effect is clinically important; a fall in LV&#xD;
      mass index of one SD has been shown to be associated with a 38% reduction in cardiovascular&#xD;
      mortality.&#xD;
&#xD;
      With respect to telomere shortening, assuming mean and SD of base pair length of 5500 and 530&#xD;
      the study will be able to detect a difference of 0.612 SD, i.e. 324 base pairs. A sample size&#xD;
      of 50 patients per group would provide a 85% power to detect a difference.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 23, 2017</start_date>
  <completion_date type="Actual">July 31, 2020</completion_date>
  <primary_completion_date type="Actual">March 20, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Left ventricular mass and interstitial fibrosis</measure>
    <time_frame>3 years</time_frame>
    <description>Measured by CMR (part 1 of study).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Aortic compliance</measure>
    <time_frame>3 years</time_frame>
    <description>Measured by CMR (part 1 of study).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular age</measure>
    <time_frame>3 years</time_frame>
    <description>Measured by telomere length and studies of DNA damage (part 1 and 2 of study).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxidative stress, inflammation and collagen turnover</measure>
    <time_frame>3 years</time_frame>
    <description>Measured by assay and bioassay (part 1 of study).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>3 years</time_frame>
    <description>Measured by ambulatory blood pressure monitoring (part 1 of study).</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">95</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <condition>Hypertrophy, Left Ventricular</condition>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Donors</arm_group_label>
    <description>Patients who donated a kidney and took part in the original CRIB-DONOR study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Healthy subjects who took part in the original CRIB-DONOR study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Nephrectomy</intervention_name>
    <description>This is observational in design.</description>
    <arm_group_label>Donors</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum, plasma, acellular urine and DNA (for telomere length).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Living donors and healthy controls&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All patients who took part in the original CRIB-Donor study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Pregnant women&#xD;
&#xD;
        Patients will have previously met nationally set criteria for living donation which&#xD;
        excludes those with:&#xD;
&#xD;
        Diabetes mellitus Atrial fibrillation Left ventricular dysfunction (ejection fraction &lt;40%&#xD;
        on transthoracic echocardiography) History of cardiovascular or pulmonary disease Evidence&#xD;
        of hypertensive end-organ damage.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Professor John Townend, MbChB</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Birmingham NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <last_update_submitted>October 2, 2020</last_update_submitted>
  <last_update_submitted_qc>October 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital Birmingham NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Anna Price</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Hypertrophy, Left Ventricular</mesh_term>
    <mesh_term>Hypertrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02973607
org study id: RRK5913
nct id: NCT02973607
lead sponsor: 
has dmc: No
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.
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.
observational model: Cohort
time perspective: Other
measure: Left ventricular mass and interstitial fibrosis
time frame: 3 years
description: Measured by CMR (part 1 of study).
measure: Aortic compliance
time frame: 3 years
description: Measured by CMR (part 1 of study).
measure: Cardiovascular age
time frame: 3 years
description: Measured by telomere length and studies of DNA damage (part 1 and 2 of study).
measure: Oxidative stress, inflammation and collagen turnover
time frame: 3 years
description: Measured by assay and bioassay (part 1 of study).
measure: Blood pressure
time frame: 3 years
description: Measured by ambulatory blood pressure monitoring (part 1 of study).
arm group label: Donors
description: Patients who donated a kidney and took part in the original CRIB-DONOR study.
arm group label: Controls
description: Healthy subjects who took part in the original CRIB-DONOR study.
intervention type: Procedure
intervention name: Nephrectomy
description: This is observational in design.
arm group label: Donors
Serum, plasma, acellular urine and DNA (for telomere length).
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Professor John Townend, MbChB
role: Principal Investigator
affiliation: University Hospital Birmingham NHS Foundation Trust
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University Hospital Birmingham NHS Foundation Trust
investigator full name: Anna Price
investigator title: Principal Investigator
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Hypertrophy, Left Ventricular
mesh term: Hypertrophy
sharing ipd: No