Clinical trial NCT02286258: Validation of New Markers of Glomerular Filtration Rate: Dota Gadolinium and Calcium EDTA (MultiGFR)
Official title: MultiGFR: Equivalency Study of Different Methods of Measuring Glomerular Filtration Rate
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Renal Insufficiency, Chronic
Kidney Diseases
Keywords: Inulin
Ca-EDTA
Gd-DOTA
Chronic kidney disease
glomerular filtration rate measurement
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2014-11-07
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

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.

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).

Eligibility 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)

Primary outcomes:
measure: Calcium EDTA and Gd-DOTA clearance for glomerular filtration rate measurement
timeFrame: 1 day
Secondary outcomes:
measure: Calcium EDTA and Gd-DOTA clearance for glomerular filtration rate measurement in each CKD stage
timeFrame: 1 day
measure: Calcium EDTA and Gd-DOTA clearance reproducibility for GFR measurement
timeFrame: 15 days
measure: Calcium EDTA and Gd-DOTA clearance with single injection for GFR measurement
timeFrame: 15 days
measure: Volumes of distribution of Calcium EDTA and Gd-DOTA
timeFrame: 1 day
measure: Number of participants with adverse events as a measure of safety.
timeFrame: 45 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou (centre d'investigations cliniques)
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou (Service de Nephrologie)
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou (service de Physiologie et des Radioisotopes)
city: Toulouse
country: France
facility: CHU Rangueil (service explorations fonctionnelles physiologiques)
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Marie Courbebaisse, Doctor
role: PRINCIPAL_INVESTIGATOR
References: