Local Haemodynamic Effects of Apelin Agonists and Antagonists in Man in Vivo (HEAP)

Apelins are substances which occur naturally in the body, and have an important role in heart disease. They have been shown to make blood vessels dilate, and improve the way the heart works.

The investigators have devised 2 sets of experiments to investigate how the apelins affect blood vessels.

In the first group of experiments,the investigators will give healthy volunteers up to 3 different apelin substances, and use special research techniques to see how they affect the way that blood vessels work in the forearm.

In the second group of experiments, the apelins will be given along with another form of apelin which blocks the effects of apelin in laboratory experiments. The investigators want to see if it blocks the effects of apelin in healthy humans.

The investigators intend to test the hypothesis that:

Apelin agonists are vasodilators in human resistance vessels, this effect will be blocked by an apelin receptor antagonist.

This study will help us to understand more about how apelins work, and to suggest how they might be used to treat heart disease.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Procedure: Forearm venous occlusion plethysmography; Procedure: Aellig hand vein technique; Other: Apelin agonist infusion; Other: Apelin receptor antagonist infusion

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Vascular Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Between 18 and 70 years
• Non-regular smoking (<5 cigarettes per week)
• If female, postmenopausal or on days 2-9 of menstrual cycle

Exclusion Criteria:

• Hypertension (sustained BP >160/100mmHg)
• Ischaemic Heart Disease
• Renal, respiratory or neurological disease
• Diabetes mellitus
• BMI >30, BMI <18
• Pregnant
• Smoker
• Use of vasoactive medication or NSAIDS/aspirin within 48 hours of study.
• Current involvement in other research studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apelin agonist infusion; Studies to measure change in blood flow in response to apelin agonists (1/10/100nmol) using forearm venous occlusion plethysmography and Aellig hand vein technique.	Procedure: Forearm venous occlusion plethysmography; Forearm venous occlusion plethysmography to study to measure forearm blood flow during intra-arterial infusion of the apelin peptides.; Procedure: Aellig hand vein technique; Hand vein measurements will be used to assess the response to apelin peptides and apelin receptor blocker in the human hand vein vascular bed.; Other: Apelin agonist infusion; Escalating doses of apelin (1/10/100nmol/min) will be administered.
Experimental: Apelin receptor antagonist infusion; Aellig hand vein technique will be used to investigate the change in vein diameter in response to an apelin blocking agent	Procedure: Aellig hand vein technique; Hand vein measurements will be used to assess the response to apelin peptides and apelin receptor blocker in the human hand vein vascular bed.; Other: Apelin receptor antagonist infusion; Dose finding study (range 1-300nmol/min) and co-infusion study with apelin peptides
Experimental: Apelin agonist/antagonist co-infusion; Forearm blood flow study to measure blood flow by forearm venous occlusion plethysmography following intraarterial infusion of apelin receptor agonists and antagonist.	Procedure: Forearm venous occlusion plethysmography; Forearm venous occlusion plethysmography to study to measure forearm blood flow during intra-arterial infusion of the apelin peptides.; Other: Apelin agonist infusion; Escalating doses of apelin (1/10/100nmol/min) will be administered.; Other: Apelin receptor antagonist infusion; Dose finding study (range 1-300nmol/min) and co-infusion study with apelin peptides

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Forearm blood flow measured by forearm plethysmography in response to infused vasodilators	2-3 hours
Change in hand vein diameter measured by Aellig hand vein technique, in response to study peptides	2-3 hours

Collaborators and Investigators

• Sponsor: University of Cambridge
• Investigators: Study Director: Ian B Wilkinson, FRCP DM, University of Cambridge; Study Director: Anthony P Davenport, MA PhD, University of Cambridge

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: May 27, 2014
• First Submitted That Met QC Criteria: May 29, 2014
• First Posted (Estimate): May 30, 2014

Study Record Updates

• Last Update Posted (Estimate): May 30, 2014
• Last Update Submitted That Met QC Criteria: May 29, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: HEAP Study