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

Condition(s) targeted: Renal Insufficiency, Chronic; Kidney Diseases

Intervention: Calcium EDTA (Drug); Gd-DOTA (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Assistance Publique - Hôpitaux de Paris

Official(s) and/or principal investigator(s):
Marie Courbebaisse, Doctor, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris

Overall contact:
Marie Courbebaisse, Doctor, Phone: 1 56 09 39 73, Ext: 33, Email: marie.courbebaisse@egp.aphp.fr

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.

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Primary outcome: Calcium EDTA and Gd-DOTA clearance for glomerular filtration rate measurement

Secondary outcome:

Calcium EDTA and Gd-DOTA clearance for glomerular filtration rate measurement in each CKD stage

Calcium EDTA and Gd-DOTA clearance reproducibility for GFR measurement

Calcium EDTA and Gd-DOTA clearance with single injection for GFR measurement

Volumes of distribution of Calcium EDTA and Gd-DOTA

Number of participants with adverse events as a measure of safety.

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).

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

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)

Marie Courbebaisse, Doctor, Phone: 1 56 09 39 73, Ext: 33, Email: marie.courbebaisse@egp.aphp.fr

Hopital Europeen Georges Pompidou (centre d'investigations cliniques), Paris 75015, France; Recruiting
Michel Azizi, Professor, Phone: 1 56 09 29 11, Ext: 33, Email: michel.azizi@egp.aphp.fr
Anne Blanchard, Doctor, Phone: 1 56 09 29 13, Ext: 33, Email: anne.blanchard@egp.aphp.fr

Hopital Europeen Georges Pompidou (Service de Nephrologie), Paris 75015, France; Recruiting
Alexandre Karras, Doctor, Phone: 1 56 09 37 60, Ext: 33, Email: alexandre.karras@egp.aphp.fr

Hopital Europeen Georges Pompidou (service de Physiologie et des Radioisotopes), Paris 75015, France; Recruiting
Marie Courbebaisse, Doctor, Phone: 1 56 09 39 73, Ext: 33, Email: marie.courbebaisse@egp.aphp.fr
Stephanie Baron, Phone: 1 56 09 26 75, Ext: 33, Email: stephanie.baron@egp.aphp.fr

CHU Rangueil (service explorations fonctionnelles physiologiques), Toulouse 31059, France; Recruiting
Ivan Tack, Professor, Phone: 5 61 32 26 83, Ext: 33, Email: tack.i@chu-toulouse.fr

Starting date: October 2014
Last updated: July 20, 2015