Local Haemodynamic Effects of Apelin Agonists and Antagonists in Man in Vivo

NCT02150694 | Completed

• 1 other identifier: HEAP Study
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiovascular Disease

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (3)

Apelin agonist infusion

EXPERIMENTAL

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; Procedure: Aellig hand vein technique; Other: Apelin agonist infusion

Apelin receptor antagonist infusion

EXPERIMENTAL

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; Other: Apelin receptor antagonist infusion

Apelin agonist/antagonist co-infusion

EXPERIMENTAL

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; Other: Apelin agonist infusion; Other: Apelin receptor antagonist infusion

Interventions

Forearm venous occlusion plethysmography PROCEDURE

Forearm venous occlusion plethysmography to study to measure forearm blood flow during intra-arterial infusion of the apelin peptides.

Apelin agonist infusion; Apelin agonist/antagonist co-infusion

Aellig hand vein technique PROCEDURE

Hand vein measurements will be used to assess the response to apelin peptides and apelin receptor blocker in the human hand vein vascular bed.

Apelin agonist infusion; Apelin receptor antagonist infusion

Apelin agonist infusion OTHER

Escalating doses of apelin (1/10/100nmol/min) will be administered.

Apelin agonist infusion; Apelin agonist/antagonist co-infusion

Apelin receptor antagonist infusion OTHER

Dose finding study (range 1-300nmol/min) and co-infusion study with apelin peptides

Apelin agonist/antagonist co-infusion; Apelin receptor antagonist infusion

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Cambridge: lead

Study Sites (1)

Vascular Research Unit

Cambridge, CB2 0QQ, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Study Officials

• Ian B Wilkinson, FRCP DM

  University of Cambridge

  STUDY DIRECTOR

• Anthony P Davenport, MA PhD

  University of Cambridge

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Fellow

Study Record Dates

• First Submitted: May 27, 2014
• First Posted: May 30, 2014
• Study Start: January 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: May 30, 2014

Record last verified: 2014-05

Locations

GB (1)