<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/NCT02969200</url>
  </required_header>
  <id_info>
    <org_study_id>FAB-KIDNEY</org_study_id>
    <nct_id>NCT02969200</nct_id>
  </id_info>
  <brief_title>Fabry: Renal Function During Long-term ERT by 51Cr-EDTA Clearance</brief_title>
  <official_title>Fabry Disease: Renal Function During Long-term Enzyme Replacement Therapy Evaluated by Gold Standard GFR 51Cr-EDTA Clearance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ulla Feldt-Rasmussen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study was to investigate renal function decline by measured glomerular&#xD;
      filtration rate (mGFR) in patients with FD during enzyme replacement therapy, and to explore&#xD;
      the influence of age on renal function in FD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nephropathy is common in Fabry disease (FD). Renal function decline is often the first sign&#xD;
      of major organ involvement, sometimes progressing to end-stage renal failure. Available&#xD;
      studies of renal function during enzyme replacement therapy have shown inconsistent results,&#xD;
      and are based on different composition of patient materials and follow-up time.&#xD;
&#xD;
      Most investigations have used estimated glomerular filtration rate (eGFR) for evaluating&#xD;
      renal function. GFR is an important indicator of renal function. eGFR based on a serum&#xD;
      creatinine measurement is most commonly used in FD. However, this method has been shown to be&#xD;
      unreliable, as serum creatinine levels are influenced by other factors than renal function&#xD;
      such as ethnic group, muscle mass, age, hydration and diet. Performance of eGFR in detecting&#xD;
      minor changes in renal function is poor. A 10 year old review on renal function evaluation in&#xD;
      patients with FD recommended the use of GFR based on an exogenous marker, e.g. Cr-EDTA.&#xD;
      Nevertheless, only few studies have used mGFR for evaluation of renal function and to our&#xD;
      knowledge, the present study is the first to describe the rate of renal function decline with&#xD;
      consecutive mGFR values in a nationwide population of patients with FD.&#xD;
&#xD;
      Renal function declines with age in renal healthy individuals. To our knowledge, the present&#xD;
      study is the first to age-standardize renal function in patients with FD to adjust for&#xD;
      age-dependent renal deterioration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2015</start_date>
  <completion_date type="Actual">December 9, 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>measured glomerular filtration rate</measure>
    <time_frame>Assessed every 6-12 months; from baseline and up to 15 years</time_frame>
    <description>GFR was measured at least once a year by the one sample 51Cr-ethylenendiaminetetra acetic acid (EDTA) clearance technique using two (for duplicate determination) plasma samples 200 min after the injection of 4 (3.8-4.2) MBq 51Cr-EDTA. In children (&lt; 15y) the injected 51Cr-activity was 3 MBq, and the blood-samples were collected 120 min after radiotracer injection. (&lt; 5y: 2 MBq).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>urinary protein excretion</measure>
    <time_frame>Assessed every 6-12 months; from baseline and up to 15 years</time_frame>
    <description>Repeated twenty-four hour urine samples were collected by patients at home, the last 24 hours before coming to the hospital. These samples were analysed for albumin, creatinine and protein. Furthermore spot urine samples were applied and analysed for albumin, creatinine and protein. Albumin-creatinine-ratio was calculated and abnormal values were defined as &gt; 30 mg/g. Urine protein- and albumin values below detection limit (&lt; 0.04 g/L and &lt; 3 mg/L, respectively) were converted to zero for statistical analyses.</description>
  </secondary_outcome>
  <enrollment type="Actual">52</enrollment>
  <condition>Fabry Disease</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enzyme replacement therapy</intervention_name>
    <description>All patients included in the study have received enzyme replacement therapy with either agalsidase alfa and/or agalsidase beta</description>
    <other_name>Fabrazyme (agalsidase beta)</other_name>
    <other_name>Replagal (agalsidase alfa)</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with Fabry disease&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Genetically and/or enzymatically verified Fabry disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  End-stage renal disease prior to baseline (GFR &lt;15 ml/min/1.73m2, dialysis or renal&#xD;
             transplant)&#xD;
&#xD;
          -  Patient has not received enzyme replacement therapy during follow-up&#xD;
&#xD;
          -  Patient has had less than 3 measurement of GFR during follow-up&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ulla V Feldt-Rasmussen, MD, DMSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National University Hospital, Department of Medical Endocrinology</name>
      <address>
        <city>Copenhagen</city>
        <zip>DK-2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>November 2, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <last_update_submitted>October 15, 2018</last_update_submitted>
  <last_update_submitted_qc>October 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 16, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Ulla Feldt-Rasmussen</investigator_full_name>
    <investigator_title>Professor, Chief physician</investigator_title>
  </responsible_party>
  <keyword>Fabry Disease</keyword>
  <keyword>Nephropathy</keyword>
  <keyword>Measured GFR</keyword>
  <keyword>Enzyme replacement therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fabry Disease</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/NCT02969200
org study id: FAB-KIDNEY
nct id: NCT02969200
lead sponsor: 
has dmc: Yes
The aim of this study was to investigate renal function decline by measured glomerular
      filtration rate (mGFR) in patients with FD during enzyme replacement therapy, and to explore
      the influence of age on renal function in FD.
Nephropathy is common in Fabry disease (FD). Renal function decline is often the first sign
      of major organ involvement, sometimes progressing to end-stage renal failure. Available
      studies of renal function during enzyme replacement therapy have shown inconsistent results,
      and are based on different composition of patient materials and follow-up time.

      Most investigations have used estimated glomerular filtration rate (eGFR) for evaluating
      renal function. GFR is an important indicator of renal function. eGFR based on a serum
      creatinine measurement is most commonly used in FD. However, this method has been shown to be
      unreliable, as serum creatinine levels are influenced by other factors than renal function
      such as ethnic group, muscle mass, age, hydration and diet. Performance of eGFR in detecting
      minor changes in renal function is poor. A 10 year old review on renal function evaluation in
      patients with FD recommended the use of GFR based on an exogenous marker, e.g. Cr-EDTA.
      Nevertheless, only few studies have used mGFR for evaluation of renal function and to our
      knowledge, the present study is the first to describe the rate of renal function decline with
      consecutive mGFR values in a nationwide population of patients with FD.

      Renal function declines with age in renal healthy individuals. To our knowledge, the present
      study is the first to age-standardize renal function in patients with FD to adjust for
      age-dependent renal deterioration.
observational model: Cohort
time perspective: Retrospective
measure: measured glomerular filtration rate
time frame: Assessed every 6-12 months; from baseline and up to 15 years
description: GFR was measured at least once a year by the one sample 51Cr-ethylenendiaminetetra acetic acid (EDTA) clearance technique using two (for duplicate determination) plasma samples 200 min after the injection of 4 (3.8-4.2) MBq 51Cr-EDTA. In children (< 15y) the injected 51Cr-activity was 3 MBq, and the blood-samples were collected 120 min after radiotracer injection. (< 5y: 2 MBq).
measure: urinary protein excretion
time frame: Assessed every 6-12 months; from baseline and up to 15 years
description: Repeated twenty-four hour urine samples were collected by patients at home, the last 24 hours before coming to the hospital. These samples were analysed for albumin, creatinine and protein. Furthermore spot urine samples were applied and analysed for albumin, creatinine and protein. Albumin-creatinine-ratio was calculated and abnormal values were defined as > 30 mg/g. Urine protein- and albumin values below detection limit (< 0.04 g/L and < 3 mg/L, respectively) were converted to zero for statistical analyses.
intervention type: Drug
intervention name: Enzyme replacement therapy
description: All patients included in the study have received enzyme replacement therapy with either agalsidase alfa and/or agalsidase beta
other name: Fabrazyme (agalsidase beta)
other name: Replagal (agalsidase alfa)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Ulla V Feldt-Rasmussen, MD, DMSc
role: Principal Investigator
affiliation: Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet
facility: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Ulla Feldt-Rasmussen
investigator title: Professor, Chief physician
mesh term: Fabry Disease
sharing ipd: No