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

NCT ID: NCT02286258

Last Updated: 2018-05-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2017-02-28

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).

Conditions

Renal Insufficiency, Chronic; Kidney Diseases

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Inuline - Calcium EDTA

Calcium EDTA clearance for GFR measurement is compared to inuline clearance in healthy volunteers and CKD patients (stage 1 to 4).

Group Type: EXPERIMENTAL

Calcium EDTA

Intervention Type: DRUG

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

Inuline - Gd-DOTA

Gd-DOTA clearance for GFR measurement is compared to inuline clearance in healthy volunteers and CKD patients (stage 1 to 4).

Group Type: EXPERIMENTAL

Gd-DOTA

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Edetic Acid, Calcium, Sodium Salt; Edetate Disodium Calcium; gadoterate; dotarem; Dota gadolinium

Eligibility Criteria

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

• 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

• 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 :

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie Courbebaisse, Doctor

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hopital Europeen Georges Pompidou (centre d'investigations cliniques)

Paris, , France

Hopital Europeen Georges Pompidou (Service de Nephrologie)

Paris, , France

Hopital Europeen Georges Pompidou (service de Physiologie et des Radioisotopes)

Paris, , France

CHU Rangueil (service explorations fonctionnelles physiologiques)

Toulouse, , France

Countries

France

Other Identifiers

P100151

Identifier Type: -

Identifier Source: org_study_id