NCT03449251

A Series of Pilot Studies to Evaluate the haemoDynamic and mEtabolic Effects oF apelIn aNd rElaxin

A Series of Pilot Studies to Evaluate the Haemodynamic and Metabolic Effects of Apelin and Relaxin in Healthy Humans, Subjects With Increased Weight and Patients With Type 2 Diabetes Mellitus

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 170 (estimated)
• Sponsor: Cambridge University Hospitals NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Accepted

Summary

Type two diabetes mellitus (T2DM) is a common, long term metabolic disorder characterised by hyperglycaemia (high blood glucose) resulting from insulin resistance and relative insulin insufficiency. The risk of developing insulin resistance and subsequently T2DM is increased by being overweight and also through a sedentary lifestyle. As the onset can be gradual, physiological damage may have occurred prior to diagnosis. Diabetes is associated with the development of microvascular complications (diabetic nephropathy, neuropathy, and retinopathy), and macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke). While there are many treatments available for T2DM, these complications may still arise, leading to significant morbidity and mortality. There is therefore an urgent need to identify novel signalling pathways that may contribute to the development of diabetes related complications. The identification of these pathways may ultimately lead to the development of new therapies targeting better blood glucose control and preventing these subsequent complications. Both animal and human studies have indicated that two endogenous peptides, apelin and relaxin both act as vasodilators in the human cardiovascular system and could also have beneficial action in T2DM. Therefore, we aim to carry out experimental medicine studies to test this hypothesis, and explore the signalling pathway in the human vascular system.

Detailed description

An extensive body of evidence demonstrates a direct association between T2DM and cardiovascular complications and mortality. Unfortunately, current therapies for diabetes have failed to be translated into improvements in cardiovascular outcomes, highlighting an urgent need to develop novel therapeutic strategies that can ultimately achieve the dual outcome of improving glycaemic control and improving cardiovascular function. While the precise cellular mechanisms involved remain to be elucidated, we hypothesise that the apelin and relaxin pathways meet these two criteria and therefore are potential therapeutic targets in conditions of abnormal glucose metabolism and heart failure. Apelin and relaxin are safe for parenteral use as they are naturally occurring peptide hormones, have a short half-life and will be rapidly cleared. They target endogenous receptors and post-receptor signalling, and have been used in human trials without any significant side effects reported.

Conditions

• Cardiovascular Diseases
• Type 2 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Apelin	Apelin is an endogenous peptide that activate a single G-protein couple receptor. Apelin inhibits insulin secretion, decreases glucose levels and increases insulin sensitivity.
DRUG	Relaxin	Relaxin is RLN2 encoded endogenous peptide hormone, which binds to G protein coupled receptor RXFP1.
DRUG	Normal saline	Vehicle
DIAGNOSTIC_TEST	Verapamil	NO independent challenge agent
DIAGNOSTIC_TEST	LN Monomethyl arginine	Basal NO synthase inhibitor

Timeline

• Start date: 2018-03-28
• Primary completion: 2025-09-01
• Completion: 2025-09-01
• First posted: 2018-02-28
• Last updated: 2024-02-07

Locations

1 site across 1 country: United Kingdom