Effects of Apelin on the Lung Circulation in Pulmonary Hypertension

Not Applicable

• Conditions: Pulmonary Arterial Hypertension; Heart Failure
• Interventions: Drug: Apelin; Drug: Saline (Placebo)

• Registration Number: NCT01457170
• Lead Sponsor: Golden Jubilee National Hospital

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2011-10-20
• Study First Submitted QC: 2011-10-20
• Study First Posted: 2011-10-21
• Study Start: 2012-01
• Status Verified: 2013-07
• Last Update Submitted: 2013-07-12
• Last Update Posted: 2013-07-15
• Primary Completion: 2014-01
• Study Completion: 2014-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 63

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

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Apelin/Saline	Apelin	Apelin infusion then crossover to Saline infusion
Apelin/Saline	Saline (Placebo)	Apelin infusion then crossover to Saline infusion
Saline/Apelin	Saline (Placebo)	Saline infusion then crossover to Apelin infusion
Saline/Apelin	Apelin	Saline infusion then crossover to Apelin infusion

Primary Outcome Measures

Name	Time	Method
Change in pulmonary vascular resistance	5,10,15 and 30 minutes after start of infusion	We will measure the change in pulmonary vascular resistance after infusion of Apelin during right heart catheterisation

Secondary Outcome Measures

Name	Time	Method
Change in systemic vascular resistance	5,10,15 and 30 minutes after start of infusion	We will measure the change in systemic vascular resistance during infusion of Apelin
Change in Cardiac Output	5,10,15 and 30 minutes after start of infusion	We will measure the change in cardiac output after infusion of Apelin during right heart catheterisation.

Trial Locations

Locations (3)

Royal Infirmary Edinburgh; 🇬🇧 Edinburgh, United Kingdom

Hammersmith Hospital; 🇬🇧 London, United Kingdom

Golden Jubilee National Hospital; 🇬🇧 Glasgow, United Kingdom