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

Primary Purpose

Heart Disease, Heart Failure, Vasodilatation

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Apelin
Acetylcholine
Sodium nitroprusside
Systemic apelin infusion
Sponsored by
University of Edinburgh
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Heart Disease focused on measuring Renin angiotensin system, Apelin, Cardiac output, Vasodilatation

Eligibility Criteria

18 Months - 85 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sodium depletion

Normal diet

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Change in cardiac output
Change in apelin mediated vasodilatation

Secondary Outcome Measures

Change in systemic haemodynamics
Change in relevant neurohumoral hormones

Full Information

First Posted
May 13, 2009
Last Updated
August 9, 2010
Sponsor
University of Edinburgh
Collaborators
NHS Lothian, British Heart Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00901719
Brief Title
Investigating Systemic and Local Vascular Responses to Apelin in the Context of Renin-angiotensin Upregulation
Official Title
Investigating the Interaction of Apelin and Systemic Angiotensin II Peripheral Resistance Vessels and Systemic Haemodynamics in Vivo in Man
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Edinburgh
Collaborators
NHS Lothian, British Heart Foundation

4. Oversight

Data Monitoring Committee
No

5. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Disease, Heart Failure, Vasodilatation
Keywords
Renin angiotensin system, Apelin, Cardiac output, Vasodilatation

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sodium depletion
Arm Type
Experimental
Arm Description
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.
Arm Title
Normal diet
Arm Type
Placebo Comparator
Arm Description
Subjects will be randomised to a normal diet, with no restriction on sodium intake during the three days prior to the study.
Intervention Type
Drug
Intervention Name(s)
Apelin
Intervention Description
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
Intervention Name(s)
Acetylcholine
Intervention Description
Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 5, 10 and 20 microg/min
Intervention Type
Drug
Intervention Name(s)
Sodium nitroprusside
Intervention Description
Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 1, 2 and 4 microg/min
Intervention Type
Drug
Intervention Name(s)
Systemic apelin infusion
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in cardiac output
Time Frame
12 months
Title
Change in apelin mediated vasodilatation
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change in systemic haemodynamics
Time Frame
12 months
Title
Change in relevant neurohumoral hormones
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Months
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
Facility Name
Clincial Research Facility, Royal Infirmary of Edinburgh, 51 Little France Cresc
City
Edinburgh
ZIP/Postal Code
EH16 4SA
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23519586
Citation
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.
Results Reference
derived

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

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