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

NCT00901719 | Completed

• 1 other identifier: FS/09/019/26905 - 3
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Keywords

Renin angiotensin system; Apelin; Cardiac output; Vasodilatation

Outcome Measures

Primary Outcomes (2)

• Change in cardiac output

  12 months

• Change in apelin mediated vasodilatation

  12 months

Secondary Outcomes (2)

• Change in systemic haemodynamics

  12 months

• Change in relevant neurohumoral hormones

  12 months

Study Arms (2)

Sodium depletion

EXPERIMENTAL

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; Drug: Acetylcholine; Drug: Sodium nitroprusside; Drug: Systemic apelin infusion

Normal diet

PLACEBO COMPARATOR

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

Drug: Apelin; Drug: Acetylcholine; Drug: Sodium nitroprusside; Drug: Systemic apelin infusion

Interventions

Apelin 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.

Normal diet; Sodium depletion

Acetylcholine DRUG

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

Normal diet; Sodium depletion

Sodium nitroprusside DRUG

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

Normal diet; Sodium depletion

Systemic apelin infusion 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; Sodium depletion

Eligibility Criteria

• Age: 18 Months - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18yr

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator
• British Heart Foundation: collaborator

Study Sites (1)

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

Edinburgh, EH16 4SA, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23519586 DERIVED

MeSH Terms

Conditions

Heart Diseases; Heart Failure; Aneurysm

Interventions

Apelin; Acetylcholine; Nitroprusside

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Biological Factors; Biogenic Amines; Amines; Organic Chemicals; Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 13, 2009
• First Posted: May 14, 2009
• Study Start: April 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: August 10, 2010

Record last verified: 2009-05

Locations

GB (1)