The Role of the Kidneys and Liver in the Elimination of Glucagon

NCT ID: NCT05056584

Last Updated: 2023-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-01
• Study Completion Date: 2023-03-28

Brief Summary

The study aims to evaluate the kinetics and effect of glucagon in patients with chronic kidney disease and liver cirrhosis and matched healthy subjects, respectively.

Detailed Description

In the present project the investigators wish to identify whether the effect, elimination and degradation of glucagon differ between healthy control subjects and patients with Chronic Kidney Disease (CKD) and liver cirrhosis, respectively. By performing glucagon infusions on healthy control subjects and matched subjects with either limited renal and hepatic function, the contribution of both organs to the metabolic clearance rate (MCR) of glucagon can be tested. A primed infusion of stable isotopic labelled tracers will allow the researchers to investigate the effects of the glucagon infusion on the glucose, lipid and amino acid metabolism.

The quantification of the MCR of glucagon will be accompanied by a range of pharmacodynamic measures in order to substantiate whether a potentially altered glucagon MCR inflicts pharmacodynamic changes of glucagon, which could contribute to the pathophysiology of CKD and liver cirrhosis.

Conditions

Chronic Kidney Diseases; Liver Cirrhosis; Hyperglucagonemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy control subjects

Healthy control subjects, matched for age, sex and BMI

Group Type: EXPERIMENTAL

Glucagon infusion

Intervention Type: BIOLOGICAL

One hour glucagon-clamp followed by one hour of blood sampling

Primed tracer infusion

Intervention Type: BIOLOGICAL

Infusion of primed isotopically labelled glucose, amino acids and lipids. From 2 hours prior to glucagon infusion and throughout the test day,

Patients with End-stage Renal Disease

Patients with hemodialysis-treated ESRD.

Group Type: EXPERIMENTAL

Glucagon infusion

Intervention Type: BIOLOGICAL

One hour glucagon-clamp followed by one hour of blood sampling

Primed tracer infusion

Intervention Type: BIOLOGICAL

Infusion of primed isotopically labelled glucose, amino acids and lipids. From 2 hours prior to glucagon infusion and throughout the test day,

Patients with liver cirrhosis

Patients with Child-Pugh A or B Cirrhosis

Group Type: EXPERIMENTAL

Glucagon infusion

Intervention Type: BIOLOGICAL

One hour glucagon-clamp followed by one hour of blood sampling

Primed tracer infusion

Intervention Type: BIOLOGICAL

Infusion of primed isotopically labelled glucose, amino acids and lipids. From 2 hours prior to glucagon infusion and throughout the test day,

Interventions

Glucagon infusion

One hour glucagon-clamp followed by one hour of blood sampling

Intervention Type: BIOLOGICAL

Primed tracer infusion

Infusion of primed isotopically labelled glucose, amino acids and lipids. From 2 hours prior to glucagon infusion and throughout the test day,

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

The CKD group

• Men/women between 18 and 75 years of age
• CKD stage 4 or 5
• Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range,
• Informed consent

The cirrhosis group

• Men/women between 18 and 75 years of age
• Verified diagnosis of cirrhosis - Child-Pugh Score of 5-12
• Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria)
• Informed consent

The control group

• Men/women between 18 and 75 years of age
• Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria)(plasma creatinine ≤105 micromol/L (µM) for men and ≤90 µM for women)
• Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range
• Informed consent

Exclusion Criteria

All groups

• Diagnosis of diabetes and/or HbA1c ≥43 mmol/mol and/or fasting plasma glucose ≥6 mmol/l.
• Previous kidney transplantation with remaining kidney graft
• Present treatment with oral glucocorticoids
• Polycystic kidney disease
• Pregnancy or breastfeeding
• Inflammatory bowel disease
• Surgical procedure within the last 3 months
• Haemoglobin < 6 mmol/l (women) or < 7 mmol/l (men)
• First-degree relatives with diabetes
• Any condition that the investigators feel would interfere with trial participation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Novo Nordisk Foundation Center for Basic Metabolic Research

OTHER

Sponsor Role: collaborator

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Magnus Frederik Gluud Grøndahl

Principal investigator, Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Filip K Knop, MD, PhD

Role: STUDY_DIRECTOR

Center for Metabolic Research, Gentofte Hospital

Magnus FG Grøndahl, MD

Role: PRINCIPAL_INVESTIGATOR

Center for Metabolic Research, Gentofte Hospital

Locations

Center for Clinical Metabolic Research, Department of Medicine, Gentofte Hospital

Hellerup, Copenhagen, Denmark

Countries

Denmark

Other Identifiers

H-16043802

Identifier Type: -

Identifier Source: org_study_id