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

NCT ID: NCT00901719

Last Updated: 2010-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2010-05-31

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.

Conditions

Heart Disease; Heart Failure; Vasodilatation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Apelin

Intervention Type: DRUG

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial apelin infusions at 0.3, 1.0 and 3.0 nanomol/ml.

Acetylcholine

Intervention Type: DRUG

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 5, 10 and 20 microg/min

Sodium nitroprusside

Intervention Type: DRUG

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 1, 2 and 4 microg/min

Systemic apelin infusion

Intervention Type: DRUG

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.

Normal diet

Subjects will be randomised to a normal diet, with no restriction on sodium intake during the three days prior to the study.

Group Type: PLACEBO_COMPARATOR

Apelin

Intervention Type: DRUG

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial apelin infusions at 0.3, 1.0 and 3.0 nanomol/ml.

Acetylcholine

Intervention Type: DRUG

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 5, 10 and 20 microg/min

Sodium nitroprusside

Intervention Type: DRUG

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 1, 2 and 4 microg/min

Systemic apelin infusion

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Acetylcholine

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 5, 10 and 20 microg/min

Intervention Type: DRUG

Sodium nitroprusside

Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 1, 2 and 4 microg/min

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Months
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

NHS Lothian

OTHER_GOV

Sponsor Role: collaborator

British Heart Foundation

OTHER

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: lead

Responsible Party

University of Edinburgh

Locations

Clincial Research Facility, Royal Infirmary of Edinburgh, 51 Little France Cresc

Edinburgh, , United Kingdom

Countries

United Kingdom

References

Barnes GD, Alam S, Carter G, Pedersen CM, Lee KM, Hubbard TJ, Veitch S, Jeong H, White A, Cruden NL, Huson L, Japp AG, Newby DE. Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure. Circ Heart Fail. 2013 May;6(3):482-91. doi: 10.1161/CIRCHEARTFAILURE.111.000077. Epub 2013 Mar 21.

Reference Type: DERIVED

PMID: 23519586 (View on PubMed)

Other Identifiers

FS/09/019/26905 - 3

Identifier Type: -

Identifier Source: org_study_id