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Validation of New Markers of Glomerular Filtration Rate: Dota Gadolinium and Calcium EDTA (MultiGFR) (MultiGFR)

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ClinicalTrials.gov Identifier: NCT02286258
Recruitment Status : Terminated (The study was suspended after a suspected unexpected serious adverse event.)
First Posted : November 7, 2014
Last Update Posted : May 18, 2018
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Study Description
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Brief Summary:
The purpose of this study is to validate in comparison to a reference method (inuline) two novel non-radioactive biomarkers for glomerular filtration rate (GFR) measurement in chronic-kidney disease (CKD) patients and in healthy volunteers: Calcium-EDTA and Gd-DOTA.

Condition or disease Intervention/treatment Phase
Renal Insufficiency, Chronic Kidney Diseases Drug: Calcium EDTA Drug: Gd-DOTA Phase 1 Phase 2

Detailed Description:

Research on estimation and measurement of renal function has been greatly stimulated by the international concept of chronic kidney disease (CKD) and its classification into stages of severity based on the level of glomerular filtration rate (GFR) (National Kidney Foundation KDOQI and ANAES in 2002, KDIGO conference in 2005), and by the development of recommendations for clinical practice according to this stages. Many efforts have focused on the validation of new formula to estimate GFR from endogenous markers. Nevertheless, the performance of these formula is limited by a large inter individual variability, that requires in many cases the use of GFR measurement using exogenous tracers (extreme anthropometric characteristics, abnormal production of endogenous tracers, potential kidney donors, dose adjustment, nephrotoxicity monitoring…). The use of GFR measurement is burdened by a lack of availability due to methodological, biological and regulatory (for radioactive tracers) constraints. That's why a need exists for new validated tracers that will be more accessible and easier to use. Moreover, there are differences between the measurement techniques: single injection of the tracer or concentration equilibrium obtained by continuous infusion; plasma or urinary clearance.

Two new tracers for GFR measurement are here offered for validation: Gd-DOTA and Calcium-EDTA. Gd-DOTA is a macrocyclic paramagnetic contrast product, which can be measured using an ELISA type immunoassay. Although being widely used in radiology with higher doses than those that will be used for GFR measurement in the multi-GFR study, Gd-DOTA has never been involved in systemic nephrogenic fibrosis cases (ProFinest study). Calcium-EDTA has been used for many years for the chelation of heavy metals. Recently, a colorimetric assay for Calcium-EDTA measurement has been developed. Gd-DOTA and Calcium-EDTA clearance for GFR measurement will be compared to inuline clearance in healthy volunteers (25 for each new tracer) and CKD patients (150 for each new tracer).

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 166 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: MultiGFR: Equivalency Study of Different Methods of Measuring Glomerular Filtration Rate
Actual Study Start Date : October 2014
Actual Primary Completion Date : February 2017
Actual Study Completion Date : February 2017

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Inuline - Calcium EDTA
Calcium EDTA clearance for GFR measurement is compared to inuline clearance in healthy volunteers and CKD patients (stage 1 to 4).
 Drug: Calcium EDTA

Calcium EDTA for equilibrium GFR measurement : bolus injection 30 mg/kg, then 10 mg/min perfusion for estimated renal clearance 100 mL /min for 4 hours.

Calcium EDTA for single injection GFR measurement : bolus injection depending on the estimated GFR

Other Names:
  • Edetic Acid, Calcium, Sodium Salt
  • Edetate Disodium Calcium
Experimental: Inuline - Gd-DOTA
Gd-DOTA clearance for GFR measurement is compared to inuline clearance in healthy volunteers and CKD patients (stage 1 to 4).
 Drug: Gd-DOTA

Gd-DOTA for equilibrium GFR measurement : bolus injection 56 ng/kg, then 28 ng/min perfusion for estimated renal clearance 100 mL /min for 4 hours.

Gd-DOTA for single injection GFR measurement : bolus injection depending on the estimated GFR

Other Names:
  • gadoterate
  • dotarem
  • Dota gadolinium


Outcome Measures
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Primary Outcome Measures :
  1. Calcium EDTA and Gd-DOTA clearance for glomerular filtration rate measurement [ Time Frame: 1 day ]
    Calcium EDTA or Gd-DOTA clearance for GFR measurement is compared to inuline clearance in healthy volunteers (n= 25) and in CKD patients (n= 150, stages 1 to 4, 30 patients for each stage) at equilibrium by measuring urinary clearances of inuline and Calcium EDTA or Gd-DOTA continuously co-infused after a loading dose.


Secondary Outcome Measures :
  1. Calcium EDTA and Gd-DOTA clearance for glomerular filtration rate measurement in each CKD stage [ Time Frame: 1 day ]
    Calcium EDTA or Gd-DOTA clearance for GFR measurement is compared to inuline clearance in healthy volunteers (n= 25) and in CKD patients (n= 150, stages 1 to 4, 30 patients for each stage) at equilibrium by measuring urinary clearances of inuline and Calcium EDTA or Gd-DOTA continuously co-infused after a loading dose.

  2. Calcium EDTA and Gd-DOTA clearance reproducibility for GFR measurement [ Time Frame: 15 days ]
    Calcium EDTA or Gd-DOTA clearance is measured twice at day 1 and day 15 in healthy volunteers (n= 25) and in CKD patients (n= 25, stages 1 to 4, 5 patients for each stage) at equilibrium by measuring urinary clearances of inuline and Calcium EDTA or Gd-DOTA continuously co-infused after a loading dose.

  3. Calcium EDTA and Gd-DOTA clearance with single injection for GFR measurement [ Time Frame: 15 days ]
    Calcium EDTA or Gd-DOTA clearance is measured twice at day 1 and day 15 in healthy volunteers (n= 25) and in CKD patients (n= 25, stages 1 to 4, 5 patients for each stage) at equilibrium at day 1 by measuring urinary clearances of inuline and Calcium EDTA or Gd-DOTA continuously co-infused after a loading dose and at day 15 with a single loading dose of Calcium EDTA or Gd-DOTA

  4. Volumes of distribution of Calcium EDTA and Gd-DOTA [ Time Frame: 1 day ]
    Calcium EDTA or Gd-DOTA apparent volumes of distribution are compared to inuline apparent volume of distribution in healthy volunteers (n= 25) and in CKD patients (n= 150, stages 1 to 4, 30 patients for each stage).

  5. Number of participants with adverse events as a measure of safety. [ Time Frame: 45 days ]
    Each event following Calcium EDTA or Gd-DOTA infusion will be listed in healthy volunteers (n = 50) and in patients (n = 300).


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Patients :

Inclusion Criteria:

  • males or females without pregnancy
  • age : 18-75
  • stable chronic kidney disease stages 1 to 4 (MDRD KDIGO 2005), estimated GFR > 15 mL/min/1.73m²
  • clinical GFR measurement indication

Exclusion Criteria:

  • kidney transplantation
  • allergic
  • acute disease leading to acute change in GFR
  • heavy metals poisoning (treated or not)
  • gadolinium contrast agent in the previous month

Healthy volunteers :

Inclusion criteria

  • males, 18-35 years old
  • weight : 60-100 kg , BMI 18-27 kg/m²
  • estimated GFR > 90 mL/min/1.73 m² (MDRD)
  • acute diseases in the previous 7 days

Exclusion criteria :

  • uro-nephrological disease (past or present)
  • nephrotoxic drug chronic use in the previous 2 months
  • allergic
  • systemic disease (acute or chronic)
Contacts and Locations
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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): NCT02286258


Locations
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France
Hopital Europeen Georges Pompidou (centre d'investigations cliniques)
Paris, France, 75015
Hopital Europeen Georges Pompidou (Service de Nephrologie)
Paris, France, 75015
Hopital Europeen Georges Pompidou (service de Physiologie et des Radioisotopes)
Paris, France, 75015
CHU Rangueil (service explorations fonctionnelles physiologiques)
Toulouse, France, 31059
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Ministry of Health, France
Investigators
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Principal Investigator: Marie Courbebaisse, Doctor Assistance Publique - Hôpitaux de Paris
More Information
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02286258    
Other Study ID Numbers: P100151
First Posted: November 7, 2014    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Inulin
Ca-EDTA
Gd-DOTA
Chronic kidney disease
glomerular filtration rate measurement
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency
Renal Insufficiency, Chronic
Urologic Diseases
Calcium, Dietary
Edetic Acid
Calcium
Calcium-Regulating Hormones and Agents
 Physiological Effects of Drugs
Bone Density Conservation Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Calcium Chelating Agents