Investigating Systemic and Local Vascular Responses to Apelin in the Context of Renin-angiotensin Upregulation

This study has been completed.
Sponsor:
Collaborators:
NHS Lothian
British Heart Foundation
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT00901719
First received: May 13, 2009
Last updated: August 9, 2010
Last verified: May 2009
  Purpose

The apelin-APJ system is a relatively new discovery. It has generated interest in part due to it's apparent ability to counteract the renin-angiotensin system, which is frequently overactive in many cardiovascular disease.

Two of the main actions of apelin are to increase the pumping ability of the heart and cause blood vessels to relax. The investigators wish to assess if these actions are altered in the setting of normal renin-angiotensin activation and increased renin-angiotensin activity.


Condition Intervention
Heart Disease
Heart Failure
Vasodilatation
Drug: Apelin
Drug: Acetylcholine
Drug: Sodium nitroprusside
Drug: Systemic apelin infusion

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Basic Science
Official Title: Investigating the Interaction of Apelin and Systemic Angiotensin II Peripheral Resistance Vessels and Systemic Haemodynamics in Vivo in Man

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Change in cardiac output [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in apelin mediated vasodilatation [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in systemic haemodynamics [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in relevant neurohumoral hormones [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: April 2010
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sodium depletion
Subjects will be randomised to normal diet or sodium depleted diet. The sodium depletion protocol comprises of a single oral dose of 40 mg of furosemide followed by an out-patient diet containing >2000 kcal of energy, >60 g of protein, <12 mmol of sodium and <70 mmol of potassium per day for 3 days prior to study. This diet is know to increase the activity of the renin-angiotensin system.
Drug: Apelin
Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial apelin infusions at 0.3, 1.0 and 3.0 nanomol/ml.
Drug: Acetylcholine
Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 5, 10 and 20 microg/min
Drug: Sodium nitroprusside
Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 1, 2 and 4 microg/min
Drug: Systemic apelin infusion
Following plethysmography patients will receive systemic infusion of (Pry)Apelin-13 (30, 100 and 300 nmol/min) for 5 mins cardiac output, blood pressure, heart rate and systemic vascular resistance will be measured at 5-min intervals.
Placebo Comparator: Normal diet
Subjects will be randomised to a normal diet, with no restriction on sodium intake during the three days prior to the study.
Drug: Apelin
Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial apelin infusions at 0.3, 1.0 and 3.0 nanomol/ml.
Drug: Acetylcholine
Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 5, 10 and 20 microg/min
Drug: Sodium nitroprusside
Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 1, 2 and 4 microg/min
Drug: Systemic apelin infusion
Following plethysmography patients will receive systemic infusion of (Pry)Apelin-13 (30, 100 and 300 nmol/min) for 5 mins cardiac output, blood pressure, heart rate and systemic vascular resistance will be measured at 5-min intervals.

  Eligibility

Ages Eligible for Study:   18 Months to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • >18yr

Exclusion Criteria:

  • Lack of informed consent
  • Age < 18 years,
  • Current involvement in other research studies,
  • Systolic blood pressure >190 mmHg or <100 mmHg
  • Malignant arrhythmias
  • Renal or hepatic failure
  • Haemodynamically significant aortic stenosis
  • Severe or significant co morbidity
  • Women of childbearing potential.
  • Any regular medication
  • Previous history of any cardiovascular disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00901719

Locations
United Kingdom
Clincial Research Facility, Royal Infirmary of Edinburgh, 51 Little France Cresc
Edinburgh, United Kingdom, EH16 4SA
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
British Heart Foundation
  More Information

No publications provided by University of Edinburgh

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Gareth Barnes, University of Edinburgh
ClinicalTrials.gov Identifier: NCT00901719     History of Changes
Other Study ID Numbers: FS/09/019/26905 - 3
Study First Received: May 13, 2009
Last Updated: August 9, 2010
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:
Renin angiotensin system
Apelin
Cardiac output
Vasodilatation

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Nitroprusside
Acetylcholine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014