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

NCT05056584 | Completed DMC

• 1 other identifier: H-16043802
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Diseases; Liver Cirrhosis; Hyperglucagonemia

Keywords

Metabolic clearance rate; Glucagon pharmacodynamics; Glucagon pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Metabolic clearance rate of glucagon

  Glucagon plasma concentration steady state glucagon concentrations

  t = 50 minutes

Secondary Outcomes (11)

• Glucagon pharmacokinetic 1

  -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes

• Glucagon pharmacokinetic 2

  -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes

• Glucagon pharmacodynamic - amino acids

  -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes

• Glucagon pharmacodynamic - glucose

  -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes

• Tracers

  -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120

Study Arms (3)

Healthy control subjects

EXPERIMENTAL

Healthy control subjects, matched for age, sex and BMI

Biological: Glucagon infusion; Biological: Primed tracer infusion

Patients with End-stage Renal Disease

EXPERIMENTAL

Patients with hemodialysis-treated ESRD.

Biological: Glucagon infusion; Biological: Primed tracer infusion

Patients with liver cirrhosis

EXPERIMENTAL

Patients with Child-Pugh A or B Cirrhosis

Biological: Glucagon infusion; Biological: Primed tracer infusion

Interventions

Glucagon infusion BIOLOGICAL

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

Healthy control subjects; Patients with End-stage Renal Disease; Patients with liver cirrhosis

Primed tracer infusion BIOLOGICAL

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

Healthy control subjects; Patients with End-stage Renal Disease; Patients with liver cirrhosis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead
• The Novo Nordisk Foundation Center for Basic Metabolic Research: collaborator

Study Sites (1)

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

Hellerup, Copenhagen, 2900, Denmark

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Fibrosis

Study Officials

• Filip K Knop, MD, PhD

  Center for Metabolic Research, Gentofte Hospital

  STUDY DIRECTOR

• Magnus FG Grøndahl, MD

  Center for Metabolic Research, Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, Medical Doctor

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: September 24, 2021
• Study Start: August 1, 2020
• Primary Completion: March 28, 2023
• Study Completion: March 28, 2023
• Last Updated: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)