Haemodynamic Effects of GLP-1 and Glucagon in Healthy Male Volunteers

NCT ID: NCT03835013

Last Updated: 2024-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-11
• Study Completion Date: 2021-11-01

Brief Summary

The study seeks to explore the cardiovascular effects of co-agonism at two peptide receptors, GLP-1 and glucagon. Glucagon, exenatide and 0.9% saline will be intravenously infused, both in isolation, and combination into healthy male participants. Overall, the aim of the study is to further our understanding on the role these endogenous substances play (both in isolation and combination) in haemodynamic regulation.

Detailed Description

Co-agonist peptides (such as at the GLP-1:glucagon receptor) are currently in clinical development for type 2 diabetes with the dual intention of reducing body weight and controlling blood glucose. However, there is a lack of data on the effects that co-agonism has on haemodynamic regulation.

Part A - Healthy male participants, by acting as their own control, will attend for two intravenous infusion visits (combination of 0.9% saline and glucagon). These will occur in a predefined but random order so that participants will be blinded to the infusion they are receiving. Each infusion visit will comprise of 15 minute baseline followed by a 120 minute infusion. Detailed non-invasive cardiovascular measurements (including peripheral/central blood pressure, heart rate, stroke volume, heart rate variability) and bloods (including insulin, glucose, GLP-1, glucagon) will be collected as part of the study. It was previously planned that GLP-1 7-36 amide 0.6pmol/kg/min and 1.2pmol/kg/min would be infused for Part A resulting in 5 infusions (rather than current 2 infusions). However due to supply/technical issues this was not possible and therefore exenatide (GLP-1 receptor agonist) shall be used in Part B.

Part B - Healthy male participants, by acting as their own control, will attend for four intravenous infusion visits (combination of 0.9% saline, glucagon, exenatide). These will occur in a predefined but random order so that participants will be blinded to the infusion they are receiving. Each infusion visit will comprise of 15 minute baseline followed by a 60 minute infusion. Detailed non-invasive cardiovascular measurements (including peripheral/central blood pressure, heart rate, stroke volume, heart rate variability) and bloods (including insulin, glucose, GLP-1, glucagon) will be collected as part of the study.

Conditions

Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Part A - Infusion A

1. 60 minute intravenous infusion of 0.9% saline

Followed by:

2. 60 minute intravenous infusion of 0.9% saline

Group Type: PLACEBO_COMPARATOR

Saline 0.9%

Intervention Type: DRUG

Intravenous infusion of 0.9% saline

Part A - Infusion B

1. 60 minute intravenous infusion of glucagon 25ng/kg/min and 0.9% saline.

Followed by:

2. 60 minute infusion of glucagon 50ng/kg/min and 0.9% saline

Group Type: ACTIVE_COMPARATOR

Saline 0.9%

Intervention Type: DRUG

Intravenous infusion of 0.9% saline

Glucagon (25ng/kg/min)

Intervention Type: DRUG

Intravenous infusion of glucagon 25ng/kg/min

Glucagon (50ng/kg/min)

Intervention Type: DRUG

Intravenous infusion of glucagon 50ng/kg/min

Part B - Infusion A

A 60 minute intravenous infusion of 0.9% saline

Group Type: ACTIVE_COMPARATOR

Saline 0.9%

Intervention Type: DRUG

Intravenous infusion of 0.9% saline

Part B - Infusion B

A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes followed by 25ng/min) and 0.9% saline

Group Type: ACTIVE_COMPARATOR

Saline 0.9%

Intervention Type: DRUG

Intravenous infusion of 0.9% saline

Exenatide

Intervention Type: DRUG

Intravenous infusion of Exenatide (loading 50ng/min for 30 minutes followed by 25ng/min for 30 minutes

Part B - Infusion C

A 60 minute intravenous infusion of glucagon (25ng/kg/min) and 0.9% saline

Group Type: ACTIVE_COMPARATOR

Saline 0.9%

Intervention Type: DRUG

Intravenous infusion of 0.9% saline

Glucagon (25ng/kg/min)

Intervention Type: DRUG

Intravenous infusion of glucagon 25ng/kg/min

Part B - Infusion D

A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes then 25ng/min) and glucagon (25ng/kg/min)

Group Type: ACTIVE_COMPARATOR

Glucagon (25ng/kg/min)

Intervention Type: DRUG

Intravenous infusion of glucagon 25ng/kg/min

Exenatide

Intervention Type: DRUG

Intravenous infusion of Exenatide (loading 50ng/min for 30 minutes followed by 25ng/min for 30 minutes

Interventions

Saline 0.9%

Intravenous infusion of 0.9% saline

Intervention Type: DRUG

Glucagon (25ng/kg/min)

Intravenous infusion of glucagon 25ng/kg/min

Intervention Type: DRUG

Glucagon (50ng/kg/min)

Intravenous infusion of glucagon 50ng/kg/min

Intervention Type: DRUG

Exenatide

Intravenous infusion of Exenatide (loading 50ng/min for 30 minutes followed by 25ng/min for 30 minutes

Intervention Type: DRUG

Other Intervention Names

Placebo; Glucagon; Glucagon

Eligibility Criteria

Inclusion Criteria

• Written informed consent to participate
• Aged 18 to 40
• Male
• Current non-smoker
• BMI >18.0 and <30kg/m2

Exclusion Criteria

• Female
• Sustained Hypertension (sustained BP >160/100mmHg) or hypotension (systolic BP below 90 mmHg)
• Clinically significant heart disease
• Implanted heart pace-maker or implantable cardioverter defibrillator (ICD)
• Known active malignancy
• Known renal failure (creatinine >140μmol/L)
• Known diabetes mellitus (type 1 or 2)
• Use of vasoactive medications or NSAIDS/aspirin within 24 hours of study visits
• Use of formal anticoagulant therapy such as, but not limited to, heparin, warfarin or rivaroxaban
• Current involvement in the active treatment phase of other research studies, (excluding observations/noninterventional)
• Any other clinical reason which may preclude entry in the opinion of the investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Dr Ian B Wilkinson

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ian Wilkinson, MA DM FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge

Locations

Addenbrooke's Hospital

Cambridge, Cambridgeshire, United Kingdom

Countries

United Kingdom

Other Identifiers

18/EM/0417

Identifier Type: OTHER

Identifier Source: secondary_id

250402

Identifier Type: OTHER

Identifier Source: secondary_id

COCOA

Identifier Type: -

Identifier Source: org_study_id