Clinical trial NCT06498063: The Underlying Mechanisms Regarding the Effect of Glucagon on the Kidneys Will be Investigated in Healthy Males.
Official title: Renal Extraction of Glucagon and Renal Effects of Glucagon
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Kidney Diseases
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: The Augustinus Foundation, Denmark.
name: The Novo Nordic Foundation
First posted: 2024-07-12
Enrollment: 10
Sex: MALE
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this crossover study is to investigate to what extend glucagon affects the kidneys. The main questions it aims to answer are:

Does glucagon regulate kidney function through extraction in the kidney in addition to glomerular filtration? Does glucagon regulate kidney function by increasing renal plasma flow and glomerular filtration rate? Does glucagon regulate kidney function by increasing renal salt excretion?

Detailed description: In patients with type 2 diabetes mellitus, plasma concentrations of glucagon are inappropriately high (hyperglucagonemia). Hyperglucagonemia has been speculated to contribute to the pathophysiology of diabetic kidney disease. Previously, glucagon has been assumed to cause glomerular hyperfiltration associated with urinary excretion of small proteins, a characteristic of early type 2 diabetic kidney injury. Further, glucagon has been shown to acutely increase urinary excretion of urea, sodium, and potassium, and patients with end-stage renal disease have elevated plasma levels of glucagon.

The purpose of this study is to clarify the underlying mechanisms behind the physiological effects of glucagon on kidney function and the kidney's ability to clear glucagon from the blood in healthy males. Specifically, the investigators aim to answer the following questions:

Does glucagon regulate kidney function through extraction in the kidney in addition to glomerular filtration? Does glucagon regulate kidney function by increasing renal plasma flow and glomerular filtration rate? Does glucagon regulate kidney function by increasing renal salt excretion?

The renal extraction of glucagon and the renal effects of glucagon will be investigated during a constant glucagon infusion in 10 healthy men aged 20-60 years. The study will be placebo-controlled. Each subject will participate in three independent and randomized trial days with a washout period of at least four weeks.

Eligibility criteria: Inclusion Criteria:

* Age: 20-60 years
* Normal health ascertained through questioning and medical examination
* Normal values for blood concentrations of fasting plasma glucose, fasting plasma total cholesterol, fasting triglycerides, HDL, LDL, creatinine, liver function, and electrolytes
* Informed consent

Exclusion Criteria:

* Immunosuppressive treatment in the preceding 12 months
* Alcohol abuse
* Medical treatment with oral glucocorticoids, dipeptidyl peptidase-4 (DPP-4) inhibitors, or GLP-1 receptor agonists, which, in the opinion of the investigator, may interfere with glucose metabolism
* Use of lithium
* Medical treatment that affects insulin secretion or cardiovascular performance measures
* Liver disease (ALT \> 2x normal value)
* Renal impairment (se-creatinine \> 130 μM and/or albuminuria)

Primary outcomes:
measure: Natriuresis
timeFrame: Analyzed from urine samples at -60, 0, 60 and 120 minutes
measure: Glucagon extraction
timeFrame: Analyzed from blood samples drawn at -30, 0, 20, 40, 60, 80, 100, 120, 140, 160 and 180 minutes
Secondary outcomes:
measure: Glomerular filtration rate
timeFrame: Measured via Fick's principle during steady state using [99mTc]Tc-DTPA (diethylene-triamine-pentaacetate) as a tracer given as a constant infusion from -210 to 180 min.
measure: Diuresis
timeFrame: Analyzed from urine samples at -60, 0, 60 and 120 minutes
measure: Renal Blood Flow
timeFrame: Measured via Fick's principle during steady state using [99mTc]Tc-DTPA (diethylene-triamine-pentaacetate) as a tracer given as a constant infusion from -210 to 180 min.
measure: Urea
timeFrame: Analyzed from blood samples drawn at -30, 0, 20, 40, 60, 80, 100, 120, 140, 160 and 180 minutes
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Physiological laboratory, Bispebjerg Hospital, Research Unit, Clinical Physiology / Nuclear Medicine Department
Study officials:
affiliation: Bispebjerg Hospital
name: Ali Asmar, MD
role: PRINCIPAL_INVESTIGATOR
References: