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

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

Detailed Description
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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.

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

Conditions
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Healthy, Chronic Kidney Disease

Intervention / Treatment
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* Drug: AcSDKP-NH2 inuline
* Drug: AcSDKP-NH2 Cr-EDTA


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AcSDKP-NH2 inuline<br>AcSDKP-NH2 inuline, Once intravenous administration of 100 µg or less | Drug: AcSDKP-NH2 inuline<br>* Once intravenous administration of 100 µg or less<br>|
| Experimental: AcSDKP-NH2 Cr-EDTA<br>AcSDKP-NH2 Cr-EDTA, Once intravenous administration of 100 µg or less | Drug: AcSDKP-NH2 Cr-EDTA<br>* Once intravenous administration of 100 µg or less<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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