Interaction of Apelin and Angiotensin in the Human Forearm Circulation

Sponsor

University of Edinburgh (Other)

Overall Status

Completed

CT.gov ID

NCT00901888

Collaborator

NHS Lothian (Other)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Angiotensin has a powerful ability to cause blood vessels constrict and reduces their diameter. One of the actions of apelin is to cause blood vessels to relax and the investigators specifically wish test the hypothesis that apelin will cause blood vessels constricted by angiotensin II to relax.

Condition or Disease	Intervention/Treatment	Phase
Heart Disease Vasodilation	Drug: Apelin infusion Drug: Sodium nitroprusside infusion	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Investigating the Interaction of Apelin and Angiotensin II Peripheral Resistance Vessels in Vivo in Man

Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

May 1, 2010

Actual Study Completion Date :

May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Angiotensin II infusion Using forearm venous occlusion plethysmography angiotensin II will be infused to cause reduction in forearm blood flow. Infusion of apelin and sodium nitroprusside will given and vasodilatation will be assessed. Blood samples for the infused arm and contra-lateral arm will be taken at regular time points to assess local and systemic changes in relevant hormones.	Drug: Apelin infusion Infusion of up to 10picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins. Drug: Sodium nitroprusside infusion Infusion of up to 150-600picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins.
Active Comparator: Noradrenaline Using forearm venous occlusion plethysmography noradrenaline will be infused to cause reduction in forearm blood flow. Infusion of apelin and sodium nitroprusside will given and vasodilatation will be assessed. Blood samples for the infused arm and contra-lateral arm will be taken at regular time points to assess local and systemic changes in relevant hormones.	Drug: Apelin infusion Infusion of up to 10picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins. Drug: Sodium nitroprusside infusion Infusion of up to 150-600picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins.

Arm

Intervention/Treatment

Experimental: Angiotensin II infusion

Using forearm venous occlusion plethysmography angiotensin II will be infused to cause reduction in forearm blood flow. Infusion of apelin and sodium nitroprusside will given and vasodilatation will be assessed. Blood samples for the infused arm and contra-lateral arm will be taken at regular time points to assess local and systemic changes in relevant hormones.

Drug: Apelin infusion

Infusion of up to 10picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins.

Drug: Sodium nitroprusside infusion

Infusion of up to 150-600picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins.

Active Comparator: Noradrenaline

Using forearm venous occlusion plethysmography noradrenaline will be infused to cause reduction in forearm blood flow. Infusion of apelin and sodium nitroprusside will given and vasodilatation will be assessed. Blood samples for the infused arm and contra-lateral arm will be taken at regular time points to assess local and systemic changes in relevant hormones.

Drug: Apelin infusion

Drug: Sodium nitroprusside infusion

Outcome Measures

Primary Outcome Measures

Change in apelin mediated forearm blood flow [12 months]

Secondary Outcome Measures

Change in local and systemic plasma apelin concentration in response angiotensin II infusion [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

18 years old

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

Locations

	Site	City	State	Country	Postal Code
1	Clincial Research Facility, Royal Infirmary of Edinburgh, 51 Little France Cresc	Edinburgh		United Kingdom	EH16 4SA

Sponsors and Collaborators

University of Edinburgh
NHS Lothian

Investigators

Principal Investigator: Gareth D Barnes, MBChB, University of Edinburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00901888

Other Study ID Numbers:

FS/09/019/26905 - 1a

First Posted:

May 14, 2009

Last Update Posted:

Aug 10, 2010

Last Verified:

Aug 1, 2010

Keywords provided by , ,

Renin Angiotensin System

Additional relevant MeSH terms:

Heart Diseases

Nitroprusside

Study Results

No Results Posted as of Aug 10, 2010