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

NHS Foundation Trust

Status: Completed

Conditions: Cardiovascular Diseases

Treatments: Drug: Exenatide; Drug: Glucagon (50ng/kg/min); Drug: Saline 0.9%; Drug: Glucagon (25ng/kg/min)

Study type: Interventional

Funder types: Other

Identifiers

NCT03835013

COCOA

18/EM/0417 (Other Identifier)

250402 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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26 participants in 6 patient groups, including a placebo group

Part A - Infusion A

Placebo Comparator group

Description:

1. 60 minute intravenous infusion of 0.9% saline Followed by: 2. 60 minute intravenous infusion of 0.9% saline

Treatment:

Drug: Saline 0.9%

Part A - Infusion B

Active Comparator group

Description:

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

Treatment:

Drug: Glucagon (25ng/kg/min)

Drug: Saline 0.9%

Drug: Glucagon (50ng/kg/min)

Part B - Infusion A

Active Comparator group

Description:

A 60 minute intravenous infusion of 0.9% saline

Treatment:

Drug: Saline 0.9%

Part B - Infusion B

Active Comparator group

Description:

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

Treatment:

Drug: Saline 0.9%

Drug: Exenatide

Part B - Infusion C

Active Comparator group

Description:

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

Treatment:

Drug: Glucagon (25ng/kg/min)

Drug: Saline 0.9%

Part B - Infusion D

Active Comparator group

Description:

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

Treatment:

Drug: Glucagon (25ng/kg/min)

Drug: Exenatide