Effects of Apelin on the Lung Circulation in Pulmonary Hypertension

Heart Failure Clinical Trial

Official title:

Investigating the Acute Pulmonary Vascular Haemodynamic Effects of Apelin in Pulmonary Hypertension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01457170
• Other study ID #: 11/CARD/04
• Status: Recruiting
• Phase: N/A
• First received: October 20, 2011
• Last updated: July 12, 2013
• Start date: January 2012
• Est. completion date: January 2014

Study information

• Verified date: July 2013
• Source: Golden Jubilee National Hospital
• Contact: Andrew J Peacock, BSc MPhil MD
• Phone: +44 (0)141 951 5497
• Email: apeacock[@]udcf.gla.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics CommitteeUnited Kingdom: National Health Service
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the effects of Apelin on the lung circulation. The investigators hypothesise that Apelin will relax the lung blood vessels and improve the pumping ability of the heart.

Description:

Apelin is an endogenous peptide with physiological actions in the cardiovascular system and is abundantly expressed in the pulmonary vasculature. Pre-clinical models and preliminary clinical data indicate that Apelin deficiency may mediate or contribute to the pathogenesis of pulmonary hypertension and heart failure. Apelin causes peripheral vasodilatation and increased cardiac contractility. The investigators will determine the effects of Apelin on the pulmonary circulation in 3 groups; healthy control, people with pulmonary arterial hypertension and people with pulmonary hypertension due to heart failure. Each subject will receive both Apelin infusion and saline placebo infusion in a crossover design. The infusions will be given in a random order which the subject and the investigator will be blinded to. The investigators hypothesise that Apelin will have more marked pulmonary haemodynamic effects than that observed in the systemic circulation. Moreover, the investigators propose that Apelin will have a marked vasodilatory effect on the human pulmonary vasculature and reduce pulmonary vascular resistance in patients with pulmonary arterial hypertension or pulmonary hypertension due to left heart disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 63
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

PULMONARY ARTERIAL HYPERTENSION

Inclusion Criteria:

• Pulmonary Arterial Hypertension which is Idiopathic, Heritable, associated with connective tissue disease or associated with drugs/toxins

• mean pulmonary artery pressure >/= 25mmHg

• pulmonary capillary wedge pressure < 15 mmHg

• normal/reduced cardiac output

• stable

• WHO functional class II - IV

Exclusion Criteria:

• significant left ventricular dysfunction

• chronic lung disease (FEV1 < 60% or abnormal CT)

• chronic thromboembolic pulmonary hypertension

HEART FAILURE

Inclusion Criteria:

• stable on treatment for 3 months prior to study

• NYHA grade II - IV

• ejection fraction <35%, left ventricular end-diastolic diameter > 5.5 cm and/or shortening fraction < 20%

• Tricuspid regurgitant velocity >/= 3.0 m/s

HEALTHY VOLUNTEERS

Inclusion Criteria:

• mean pulmonary artery pressure < 25 mmHg

• tricuspid regurgitant velocity < 2.5 m/s

Exclusion Criteria:

• obstructive coronary artery disease

ALL SUBJECTS

Exclusion Criteria:

• bleeding diathesis

• women of childbearing potential without pregnancy test

• systolic blood pressure > 190 mmHg or < 100 mmHg

• malignant arrhythmias

• renal or hepatic failure

• haemodynamically significant valvular heart disease

• severe or significant co-morbidity

• pacemaker

• already taking part in another trial

• lack of informed consent

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Heart Failure
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Apelin
During right heart catheterisation, Apelin will be infused at 30, 100 and 300 nanomol/min for 5 minutes. Apelin will then be infused at 300 nanomol/min for a further 15 minutes while the subject exercises using a supine ergometer.
• Saline (Placebo)
During right heart catheterisation, saline will be infused for 15 minutes while the subject rest and for a further 15 minutes while the subject exercises using a supine ergometer.
• Saline (Placebo)
During right heart catheterisation, saline will be infused for 15 minutes while the subject rest and for a further 15 minutes while the subject exercises using a supine ergometer.
• Apelin
During right heart catheterisation, Apelin will be infused at 30, 100 and 300 nanomol/min for 5 minutes. Apelin will then be infused at 300 nanomol/min for a further 15 minutes while the subject exercises using a supine ergometer.

Locations

Country	Name	City	State
United Kingdom	Royal Infirmary Edinburgh	Edinburgh
United Kingdom	Golden Jubilee National Hospital	Glasgow
United Kingdom	Hammersmith Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
Golden Jubilee National Hospital	Imperial College Healthcare NHS Trust, NHS Lothian

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pulmonary vascular resistance	We will measure the change in pulmonary vascular resistance after infusion of Apelin during right heart catheterisation	5,10,15 and 30 minutes after start of infusion	No
Secondary	Change in systemic vascular resistance	We will measure the change in systemic vascular resistance during infusion of Apelin	5,10,15 and 30 minutes after start of infusion	No
Secondary	Change in Cardiac Output	We will measure the change in cardiac output after infusion of Apelin during right heart catheterisation.	5,10,15 and 30 minutes after start of infusion	No