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

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:

MedlinePlus related topics: Heart Diseases Heart Failure

Drug Information available for: Acetylcholine chloride Sodium nitroprusside Nitroprusside

U.S. FDA Resources

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.

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

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

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 Diseases
Heart Failure
Flushing
Hyperemia
Hot Flashes
Cardiovascular Diseases
Signs and Symptoms
Vascular Diseases
Acetylcholine
Nitroprusside
Vasodilator Agents

Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Nitric Oxide Donors
Antihypertensive Agents

ClinicalTrials.gov processed this record on May 22, 2013