Development of a New Non-radioactive Test for Measuring Glomerular Filtration Rate Using the Tetrapeptide N-acetyl-Ser-Asp-Lys-Pro-amide (AcSDKP-NH2) (AcSDKP-NH2)

The purpose of the study is to validate a new reference marker for evaluation of renal function (glomerular filtration rate).

Study Overview

• Status: Completed
• Conditions: Healthy; Chronic Kidney Disease
• Intervention / Treatment: Drug: AcSDKP-NH2 inuline; Drug: AcSDKP-NH2 Cr-EDTA

Detailed Description

Chronic kidney disease (CKD) is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes (kidney failure, complications of decreased kidney function and cardiovascular disease), and high cost. Some of the adverse outcomes can be prevented or delayed by early detection and treatment. However, CKD is frequently underdiagnosed and undertreated. The glomerular filtration rate (GFR) is considered as the best index of renal function. The clinical action plan promoted by International Guidelines groups refers to GFR values. Despite recent improvements, prediction equations developed in order to estimate GFR elicit a huge lack of accuracy when considering the individual patient, especially in case of early CKD. Rigorous assessment of GFR requires the measurement of urinary or plasma clearance of an ideal exogenous filtration marker which is either non-radioactive (inulin, iothalamate, or iohexol) or radioactive ( 51Cr-EDTA or 99mTc DTPA. Measuring clearance with the use of exogenous markers is difficult to perform in clinical practice because it is expensive and cumbersome and needs specialised laboratories and thus, is underused. There is an unmet need for the development of a new non-radioactive GFR tracer that could combine both the analytical accuracy of radioactive tracers and the simplicity of its measurement. Such a tracer should improve clinical care and follow-up of patients.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Clinical Investigation Center, European George Pompidou Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Phase I: 18-35 years male
• Phase I: healthy volunteers
• Phase II: 18-80 years patients (both sex)
• Phase II: with Chronic Kidney Disease

Exclusion Criteria:

• Phase I: Smokers
• Phase I: Allergic

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AcSDKP-NH2 inuline; AcSDKP-NH2 inuline, Once intravenous administration of 100 µg or less	Drug: AcSDKP-NH2 inuline; Once intravenous administration of 100 µg or less
EXPERIMENTAL: AcSDKP-NH2 Cr-EDTA; AcSDKP-NH2 Cr-EDTA, Once intravenous administration of 100 µg or less	Drug: AcSDKP-NH2 Cr-EDTA; Once intravenous administration of 100 µg or less

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glomerular filtration rate	NAcSDKP clearance for GFR measurement is compared to inuline and 51Cr-EDTA clearance in two phase I studies in 50 healthy subjects. GFR is first assessed at equilibrium by measuring urinary clearances of inuline and NAcSDKP continuously co-infused after a loading dose; and second by plasma clearances of 51Cr-EDTA and NAcSDKP after a single IV bolus. Optimal conditions for using NAcSDKP as a marker for GFR and the tolerability of the peptide are assessed during these studies. Then, a phase IIa study will be performed to compare the 2 methods in 45 patients with various degrees of renal failure.	between day 7 and day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety	all adverse events (clinical or biological adverse events)	One month extended to 3 months safety follow up

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Michel AZIZI, MD, PhD, Université Paris-Descartes, Faculté de Médecine; Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques; INSERM, CIC 9201, F-75015 Paris, France

Publications and helpful links

General Publications

• Mesmin C, Cholet S, Blanchard A, Chambon Y, Azizi M, Ezan E. Mass spectrometric quantification of AcSDKP-NH2 in human plasma and urine and comparison with an immunoassay. Rapid Commun Mass Spectrom. 2012 Jan 30;26(2):163-72. doi: 10.1002/rcm.5326.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2010
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: April 2, 2012
• First Submitted That Met QC Criteria: April 27, 2012
• First Posted (ESTIMATE): May 1, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 1, 2017
• Last Update Submitted That Met QC Criteria: February 27, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Chronic kidney disease; GFR; Inulin; 51Cr-EDTA; ASDKP-NH2; Healthy male 18-35 yrs old, non smokers, non allergic; Or Male/female 18-80 yrs old with chronic Kidney disease
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Growth Substances; Growth Inhibitors; Radiation-Protective Agents; Mechlorethamine; Goralatide
• Other Study ID Numbers: AOM08193