Acute Effects of GLP-1 on Renal Hemodynamics

Not Applicable

Completed

• Conditions: The GLP-1-mediated Gut-kidney Axis
• Interventions: Drug: Glucagon-Like Peptide 1; Drug: saline 0.9%

• Registration Number: NCT04337268
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

This study investigates the hypothesis, that GLP-1's suppression of ANG II and natriuretic action increase medullary perfusion and decrease oxygen consumption, leading to higher tissue oxygenation.

Detailed Description

Human studies have recently demonstrated a significant natriuretic effect of GLP-1 when the extracellular fluid volume (ECFV) is expanded by intravenous sodium-loading; in these studies, there was a suppression of ANG II with no change in net renal hemodynamics, pointing to a tubular mechanism for reduced NaCl reabsorption secondary to the ANG II suppression. In the current randomized and controlled study, investigators aim to test the hypothesis that GLP-1's suppression of ANG II and natriuretic action increase medullary perfusion and decrease oxygen consumption, leading to higher tissue oxygenation. Thus, contributing to the renoprotective action of GLP-1.

Under fixed sodium intake for 4 days before each study day, 10 healthy male participants will be investigated during a 1-hour infusion of GLP-1 (1.5 pmol/kg/min) or vehicle together with an intravenous infusion of 0.9% NaCl. Interleaved measurements of RAF, oxygenation (T2\*) and perfusion by arterial spin labeling in the renal cortex and medulla at fixed time points will be conducted, using Magnetic Resonance Imaging (MRI).

Study Timeline

• Study Start: 2019-04-01
• Primary Completion: 2020-03-01
• Study Completion: 2020-03-01
• Study First Submitted: 2020-03-29
• Status Verified: 2020-04
• Study First Submitted QC: 2020-04-03
• Last Update Submitted: 2020-04-03
• Study First Posted: 2020-04-07
• Last Update Posted: 2020-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

Inclusion Criteria

• Normal health demonstrated by medical examination.
• Normal values for fasting plasma glucose, total cholesterol, triglyceride, HDL, LDL, creatinine, AST, ALT and electrolyte concentrations.

Exclusion Criteria

• Immunosuppressive treatment for the previous 12 months.
• Alcohol abuse.
• Medical treatment with oral glucocorticoids, dipeptidyl peptidase-4 (DPP-4) inhibitors, or GLP-1 receptor agonists that, in the opinion of the investigator, may interfere with glucose metabolism.
• Use of lithium.
• Medical treatment that affects insulin secretion or cardiovascular efficacy goals.
• Liver disease (ALT> 2 x normal value).
• Renal impairment (creatinine> 130 µM and / or albuminuria).
• Severe claustrophobia.
• MRI incompatible foreign bodies.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
human glucagon-like peptide-1	Glucagon-Like Peptide 1	Intervention: Drug: human glucagon-like peptide-1 Other names: GLP-1
Placebo	saline 0.9%	Intervention: Drug: Placebo (saline) Other names: Placebo for human glucagon-like peptide-1

Primary Outcome Measures

Name	Time	Method
Arterial Spin Labeled (ASL)	1 hour	Changes in Arterial Spin Labeled (ASL) MRI Perfusion Imaging in renal cortex and medulla
Renal Artery Flow Phase (RAF)	1 hour	Changes in Renal Artery Flow Phase (RAF)-Contrast Magnetic Resonance
T2* signal	1 hour	Changes in T2\* signal in renal cortex and medulla

Trial Locations

Locations (1)

Rigshospitalet - Glostrup; 🇩🇰 Glostrup, Copenhagen, Denmark