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

Chronic Kidney Diseases Clinical Trial

— MCR_EndCir  

Official title:

The Role of the Kidneys and Liver in the Elimination of Glucagon An Evaluation of the Metabolic Clearance Rate of Glucagon in Patients With End-stage Renal Disease and Patients With Liver Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05056584
• Other study ID #: H-16043802
• Status: Completed
• Phase: N/A
• Start date: August 1, 2020
• Est. completion date: March 28, 2023

Study information

• Verified date: May 2023
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: March 28, 2023
• Est. primary completion date: March 28, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Fibrosis
• Hyperglucagonemia
• Kidney Diseases
• Liver Cirrhosis
• Renal Insufficiency, Chronic

Intervention

Biological:
• Glucagon infusion
One hour glucagon-clamp followed by one hour of blood sampling
• 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,

Locations

Country	Name	City	State
Denmark	Center for Clinical Metabolic Research, Department of Medicine, Gentofte Hospital	Hellerup	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	The Novo Nordisk Foundation Center for Basic Metabolic Research

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metabolic clearance rate of glucagon	Glucagon plasma concentration steady state glucagon concentrations	t = 50 minutes
Secondary	Glucagon pharmacokinetic 1	Elimination half-life	-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Secondary	Glucagon pharmacokinetic 2	volume of distribution of Glucagon	-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Secondary	Glucagon pharmacodynamic - amino acids	Effect of glucagon on amino acid plasma levels before, during and after infusion	-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Secondary	Glucagon pharmacodynamic - glucose	Effect of glucagon on plasma glucose levels before, during and after infusion	-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Secondary	Tracers	Tracer-to-tracee ratio of labelled isotopes	-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120
Secondary	Insulin	Excursions of plasma concentrations of insulin	-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Secondary	Glucagon-like peptide 1	Excursions of plasma concentrations of GLP-1	-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Secondary	Lipid metabolism	Effect of glucagon on lipid metabolism, through lipidomics	-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Secondary	Vital parameter 1	Systolic blood pressure	-120, -30, 0, 60, 120 minutes
Secondary	Vital parameter 2	Diastolic blood pressure	-120, -30, 0, 60, 120 minutes
Secondary	Vital parameter 3	Heart rate	-120, -30, 0, 60, 120 minutes