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

Not Applicable

Completed

• Conditions: Heart Disease; Heart Failure; Vasodilatation
• Interventions: Drug: Apelin; Drug: Acetylcholine; Drug: Sodium nitroprusside; Drug: Systemic apelin infusion

• Registration Number: NCT00901719
• Lead Sponsor: University of Edinburgh

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2009-05
• Study First Submitted: 2009-05-13
• Study First Submitted QC: 2009-05-13
• Study First Posted: 2009-05-14
• Study Start: 2010-04
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Last Update Submitted: 2010-08-09
• Last Update Posted: 2010-08-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sodium depletion	Apelin	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.
Sodium depletion	Systemic apelin infusion	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.
Normal diet	Apelin	Subjects will be randomised to a normal diet, with no restriction on sodium intake during the three days prior to the study.
Normal diet	Systemic apelin infusion	Subjects will be randomised to a normal diet, with no restriction on sodium intake during the three days prior to the study.
Sodium depletion	Sodium nitroprusside	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.
Normal diet	Sodium nitroprusside	Subjects will be randomised to a normal diet, with no restriction on sodium intake during the three days prior to the study.
Sodium depletion	Acetylcholine	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.
Normal diet	Acetylcholine	Subjects will be randomised to a normal diet, with no restriction on sodium intake during the three days prior to the study.

Primary Outcome Measures

Name	Time	Method
Change in cardiac output	12 months
Change in apelin mediated vasodilatation	12 months

Secondary Outcome Measures

Name	Time	Method
Change in systemic haemodynamics	12 months
Change in relevant neurohumoral hormones	12 months

Trial Locations

Locations (1)

Clincial Research Facility, Royal Infirmary of Edinburgh, 51 Little France Cresc; 🇬🇧 Edinburgh, United Kingdom