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

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.

Conditions

• Cardiovascular Diseases
• Type 2 Diabetes Mellitus

Interventions

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

Sponsors & Collaborators

• University of Cambridge

  collaborator OTHER

• AstraZeneca

  collaborator INDUSTRY

• MedImmune LLC

  collaborator INDUSTRY

• Cambridge University Hospitals NHS Foundation Trust

  lead OTHER

Principal Investigators

• Joseph Cheriyan, MBCHB, FRCP · Cambridge University Hospitals NHS Foundation Trust

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-03-28

Primary Completion

2025-09-30

Completion

2025-09-30

Countries

• United Kingdom

Study Locations