The Underlying Mechanisms Regarding the Effect of Glucagon on the Kidneys Will be Investigated in Healthy Males.

NCT ID: NCT06498063

Last Updated: 2024-07-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-20

Study Completion Date

2025-07-31

Brief Summary

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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

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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.

Conditions

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Kidney Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Glucagon+Exendin9-39

Glucagon (infusion of 5 ng·kg-1·min-1 from 0-60 minutes) and glucagon (infusion of 10 ng·kg-1 ·min-1 from 60-120 minutes) + a GLP-1R antagonist, exendin 9-39 (900 pmol·kg-1·min-1 from -30-120 minutes).

Group Type EXPERIMENTAL

Glucagon

Intervention Type OTHER

Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.

Placebo

Intervention Type OTHER

Placebo (0.9% NaCl).

Glucagon and exendin 9-39

Intervention Type OTHER

Glucagon (infusion of 5 ng·kg-1·min-1 from 0-60 minutes) and glucagon (infusion of 10 ng·kg-1 ·min-1 from 60-120 minutes) + a GLP-1R antagonist, exendin 9-39 (900 pmol·kg-1·min-1 from -30-120 minutes).

Sodium chloride (Placebo comparator)

NaCl (0.9%)

Group Type PLACEBO_COMPARATOR

Glucagon

Intervention Type OTHER

Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.

Placebo

Intervention Type OTHER

Placebo (0.9% NaCl).

Glucagon and exendin 9-39

Intervention Type OTHER

Glucagon (infusion of 5 ng·kg-1·min-1 from 0-60 minutes) and glucagon (infusion of 10 ng·kg-1 ·min-1 from 60-120 minutes) + a GLP-1R antagonist, exendin 9-39 (900 pmol·kg-1·min-1 from -30-120 minutes).

Glucagon

Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.

Group Type EXPERIMENTAL

Glucagon

Intervention Type OTHER

Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.

Placebo

Intervention Type OTHER

Placebo (0.9% NaCl).

Glucagon and exendin 9-39

Intervention Type OTHER

Glucagon (infusion of 5 ng·kg-1·min-1 from 0-60 minutes) and glucagon (infusion of 10 ng·kg-1 ·min-1 from 60-120 minutes) + a GLP-1R antagonist, exendin 9-39 (900 pmol·kg-1·min-1 from -30-120 minutes).

Interventions

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Glucagon

Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.

Intervention Type OTHER

Placebo

Placebo (0.9% NaCl).

Intervention Type OTHER

Glucagon and exendin 9-39

Glucagon (infusion of 5 ng·kg-1·min-1 from 0-60 minutes) and glucagon (infusion of 10 ng·kg-1 ·min-1 from 60-120 minutes) + a GLP-1R antagonist, exendin 9-39 (900 pmol·kg-1·min-1 from -30-120 minutes).

Intervention Type OTHER

Eligibility Criteria

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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)
Minimum Eligible Age

20 Years

Maximum Eligible Age

60 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Copenhagen

OTHER

Sponsor Role collaborator

The Augustinus Foundation, Denmark.

OTHER

Sponsor Role collaborator

The Novo Nordic Foundation

OTHER

Sponsor Role collaborator

Ali Asmar

OTHER

Sponsor Role lead

Responsible Party

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Ali Asmar

Chief Physician, Associate Professor, PhD, MD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Ali Asmar, MD

Role: PRINCIPAL_INVESTIGATOR

Bispebjerg Hospital

Locations

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Physiological laboratory, Bispebjerg Hospital, Research Unit, Clinical Physiology / Nuclear Medicine Department

Copenhagen, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Ali Asmar, MD

Role: CONTACT

800-555-5555

Anna Billeschou Bomholt

Role: CONTACT

800-555-5555

Facility Contacts

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Anna Billeschou Bomholt, M.Sc.

Role: primary

800-555-5555

Other Identifiers

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20-1914; 21-1518

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NNF21OC0070308

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

H-22019483

Identifier Type: -

Identifier Source: org_study_id

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