Clinical trial NCT03835013: Haemodynamic Effects of GLP-1 and Glucagon in Healthy Male Volunteers
Official title: A Comparison of the Haemodynamic and Metabolic Effects of Intravenous Glucagon-like Peptide-1, Glucagon and Glucagon-like Peptide-1:Glucagon Co-agonism in Healthy Male Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2019-02-08
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A - 2 infusions Part B - 4 infusions
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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:
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
timeFrame: 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
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: Cambridgeshire
Study officials:
affiliation: University of Cambridge
name: Ian Wilkinson, MA DM FRCP
role: PRINCIPAL_INVESTIGATOR
References: