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

MultiGFR: Equivalency Study of Different Methods of Measuring Glomerular Filtration Rate

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.

Study Overview

• Status: Terminated
• Conditions: Kidney Diseases; Renal Insufficiency, Chronic
• Intervention / Treatment: Drug: Calcium EDTA; Drug: Gd-DOTA

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 Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • 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)
  • Toulouse, France, 31059
    • CHU Rangueil (service explorations fonctionnelles physiologiques)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calcium EDTA and Gd-DOTA clearance for glomerular filtration rate measurement	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.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calcium EDTA and Gd-DOTA clearance for glomerular filtration rate measurement in each CKD stage	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.	1 day
Calcium EDTA and Gd-DOTA clearance reproducibility for GFR measurement	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.	15 days
Calcium EDTA and Gd-DOTA clearance with single injection for GFR measurement	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	15 days
Volumes of distribution of Calcium EDTA and Gd-DOTA	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).	1 day
Number of participants with adverse events as a measure of safety.	Each event following Calcium EDTA or Gd-DOTA infusion will be listed in healthy volunteers (n = 50) and in patients (n = 300).	45 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Marie Courbebaisse, Doctor, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2014
• Primary Completion (ACTUAL): February 1, 2017
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: October 29, 2014
• First Submitted That Met QC Criteria: November 6, 2014
• First Posted (ESTIMATE): November 7, 2014

Study Record Updates

• Last Update Posted (ACTUAL): May 18, 2018
• Last Update Submitted That Met QC Criteria: May 15, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Chronic kidney disease; Inulin; Ca-EDTA; Gd-DOTA; glomerular filtration rate measurement
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Anticoagulants; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Calcium; Calcium, Dietary; Edetic Acid
• Other Study ID Numbers: P100151