The Effect of Acyl-Ghrelin on Kidney Function and Blood Pressure in Healthy Volunteers

Study Overview
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Brief Summary
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Ghrelin (growth hormone release inducer) is produced in the stomach. The active form of Ghrelin is Acyl-Ghrelin. Acyl-Ghrelin stimulates the Ghrelin receptors. Ghrelin receptors are detected in the distal tubules in mice and animal studies have shown that Ghrelin increases the absorption of sodium in the renal tubules. Ghrelin infusion directly into the renal artery of rats increased sodium reabsorption in the distal nephron, presumably via the epithelial sodium channels (ENaC). The purpose of the study is to measure the acyl-ghrelin induced effects on GFR, tubular transport of sodium and water in different nephron segments and central and peripheral blood pressure in a randomized, cross-over, single-blind, placebo-controlled dose-response study.

Official Title
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The Effect of Acyl-Ghrelin on Kidney Function and Blood Pressure in Healthy Volunteers - A Randomized, Cross-over, Single-blind, Placebo-controlled Dose-response Study of the Acyl-ghrelin Induced Effects on GFR, Tubular Transport of Sodium and Water in Different Nephron Segments and Central and Peripheral Blood Pressure

Conditions
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Renal Tubular Transport

Intervention / Treatment
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* Drug: Acyl-Ghrelin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-40 years, BMI 18,5-30kg/m2, women must use contraception. Exclusion Criteria: Tobacco smoking, substance abuse, consumption of more than 7 units of alcohol/week for women and more than 14 units/week for men, medical treatment except for contraception, pregnancy or nursing, allergy to acyl-ghrelin, significant clinical signs of heart-, lung-, liver-, kidney-, endocrine-, brain- or neoplastic disorders, clinically significant abnormal findings in screening blood samples, urine sample or ECG, office blood pressure over 140/90 mmHg, donation of blood within 1 month of the first day of investigation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 50 µg Acyl-Ghrelin<br>Intravenous injection on examination day. | Drug: Acyl-Ghrelin<br> <br> |
| Active Comparator: 100 µg Acyl-Ghrelin<br>Intravenous injection on examination day. | Drug: Acyl-Ghrelin<br> <br> |
| Placebo Comparator: Isotonic Sodium Chloride<br>Intravenous injection on examination day. | Drug: Acyl-Ghrelin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional sodium excreation (FENa) | Measurement of FENa at baseline and after Acyl-Ghrelin injection | 5-6 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function | Measurement of GFR, FEK and CH20 at baseline and after Acyl-Ghrelin injection | 5-6 Hours | 
| Water and sodium transport | Measurement of u-AQP2, u-NCC , u-NKCC -2 and u-ENaC at baseline and after Acyl-Ghrelin | 5-6 Hours | 
| Vasoactive hormones | Measurement of p-BNP , PRC, p-AngII , p-Aldo and p-AVP at baseline and after Acyl-Ghrelin | 5-6 Hours | 
| Blood pressure | Measurement of Central blood pressure, PWV, AIx and Peripheral blood pressure at baseline and after Acyl-Ghrelin | 5-6 Hours |