Hepatic Metabolic Changes in Response to Glucagon Infusion

NCT ID: NCT03526445

Last Updated: 2019-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-01
• Study Completion Date: 2019-06-12

Brief Summary

The objective of the study is to investigate how exogenously administered glucagon affects hepatic lipid, glucose and protein metabolism as well as appetite, food intake and resting energy expenditure.

Detailed Description

Most research has focused on the role of the pancreatic hormone, insulin, and insulin signalling (or lack of) in the development of NAFLD. However, increasing evidence suggest that the other major gluco-regulatory pancreatic hormone glucagon is also implicated in lipid metabolism and recent human data from studies investigating the effect of glucagon receptor antagonism suggest that glucagon signalling may be essential for maintaining a fat-free liver. This, combined with observations of increased degree of hepatic steatosis in patients after total pancreatectomy, who are devoid of pancreatic glucagon and typically are lean and peripherally insulin sensitive, suggests that glucagon may play a hitherto unrecognised role in the pathophysiology of NAFLD.

The hypothesis of the study is that exogenously delivered glucagon will drive hepatic metabolism in a lipolytic direction and increase resting energy expenditure without affecting appetite and food intake.

The acute effects of exogeneous glucagon infusion on hepatic lipid metabolism will be evaluated in patients after total pancreatectomy (no endogenous pancreatic hormones), in patients with type 1 diabetes (no endogenous insulin production) and in healthy controls (preserved endogenous pancreatic hormones).

Conditions

Non-Alcoholic Fatty Liver Disease; Total Pancreatectomy; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Glucagon

3 hours i.v. infusion of Glucagon (4 ng/kg/min).

Group Type: ACTIVE_COMPARATOR

Glucagon

Intervention Type: DRUG

Glucagon (4 ng/kg/min)

Saline

3 hours i.v. infusion of saline

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Placebo

Interventions

Glucagon

Glucagon (4 ng/kg/min)

Intervention Type: DRUG

Saline

Placebo

Intervention Type: DRUG

Other Intervention Names

GlucaGen

Eligibility Criteria

Inclusion Criteria

Pancreatectomised patients

• Patients who have undergone total pancreatectomy
• Caucasian between 30-80
• Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females
• Informed consent

Patients with type 1 diabetes

• Patients with C-peptide negative type 1 diabetes
• Caucasian between 30-80
• Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females
• Informed consent

Healthy controls

• Normal fasting plasma glucose (< 7 mmol/l) and normal HbA1c (< 6.5 %) (30,31)
• Normal blood haemoglobin (>8.3 mmol/l for males and >7.3 mmol/l for females)
• Caucasian between 30-80
• Informed consent

Exclusion Criteria

All subjects

• Inflammatory bowel disease
• Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy
• Nephropathy (eGFR < 60 ml/min/1.73 m² and/or urine albumin > 20 mg/L)
• Known liver disease (excluding non-alcoholic fatty liver disease)
• Severe lung disease
• Pregnancy and/or breastfeeding
• Uncontrolled hypertension and/or significant cardiovascular disease
• Treatment with drugs with potential steatogenic side-effects within three months prior to inclusion
• Alcohol consumption above 21 units/week for men and 14 units/week for women
• Any condition that the investigator feels would interfere with the safety of the trial participation or the safety of the subject.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Copenhagen

OTHER

Sponsor Role: collaborator

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Filip Krag Knop, Prof.

Role: STUDY_DIRECTOR

Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen

Locations

Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen

Hellerup, , Denmark

Countries

Denmark

Other Identifiers

H-18003696

Identifier Type: -

Identifier Source: org_study_id