Acute Effects of GLP-1 on Renal Hemodynamics (GLP1RRBF)

Rigshospitalet

Status: Completed

Conditions: The GLP-1-mediated Gut-kidney Axis

Treatments: Drug: saline 0.9%; Drug: Glucagon-Like Peptide 1

Study type: Interventional

Funder types: Other

Identifiers

NCT04337268

H-18050603

Details and patient eligibility

About

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.

Full 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).

Enrollment: 10 patients

Sex: Male

Ages: 20 to 60 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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10 participants in 2 patient groups, including a placebo group

human glucagon-like peptide-1

Active Comparator group

Description:

Intervention: Drug: human glucagon-like peptide-1 Other names: GLP-1

Treatment:

Drug: Glucagon-Like Peptide 1

Placebo

Placebo Comparator group

Description:

Intervention: Drug: Placebo (saline) Other names: Placebo for human glucagon-like peptide-1

Treatment:

Drug: saline 0.9%