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

NCT03835013 | Completed

• 3 other identifiers: COCOA18/EM/0417250402
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Diseases

Outcome Measures

Primary Outcomes (7)

• Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Heart rate (bpm)

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Brachial systolic and diastolic blood pressure (mmHg)

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Central systolic and diastolic blood pressure and mean arterial pressure (mmHg) measured with SphygmoCor XCEL

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Stroke volume (ml) measured by bioimpedance

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Cardiac output (L/min) measured by bioimpedance

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  peripheral vascular resistance (dynes/sec/cm)

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Heart rate variability (normalised low frequency, LF, high frequency, HF and LF/HF ratio)

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

Secondary Outcomes (7)

• Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Comparison between 2 hour infusion visit 1-5 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

• Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.

  Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks

Study Arms (6)

Part A - Infusion A

PLACEBO COMPARATOR

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

Drug: Saline 0.9%

Part A - Infusion B

ACTIVE COMPARATOR

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

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

Part B - Infusion A

ACTIVE COMPARATOR

A 60 minute intravenous infusion of 0.9% saline

Drug: Saline 0.9%

Part B - Infusion B

ACTIVE COMPARATOR

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

Drug: Saline 0.9%; Drug: Exenatide

Part B - Infusion C

ACTIVE COMPARATOR

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

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

Part B - Infusion D

ACTIVE COMPARATOR

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

Drug: Glucagon (25ng/kg/min); Drug: Exenatide

Interventions

Saline 0.9% DRUG

Intravenous infusion of 0.9% saline

Also known as: Placebo

Part A - Infusion A; Part A - Infusion B; Part B - Infusion A; Part B - Infusion B; Part B - Infusion C

Glucagon (25ng/kg/min) DRUG

Intravenous infusion of glucagon 25ng/kg/min

Also known as: Glucagon

Part A - Infusion B; Part B - Infusion C; Part B - Infusion D

Glucagon (50ng/kg/min) DRUG

Intravenous infusion of glucagon 50ng/kg/min

Also known as: Glucagon

Part A - Infusion B

Exenatide DRUG

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

Part B - Infusion B; Part B - Infusion D

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Sodium Chloride; Glucagon; Exenatide

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• Ian Wilkinson, MA DM FRCP

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Part A - 2 infusions Part B - 4 infusions

Study Record Dates

• First Submitted: January 25, 2019
• First Posted: February 8, 2019
• Study Start: February 11, 2019
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: April 3, 2024

Record last verified: 2024-04

Locations

GB (1)