Effects of Apelin on the Lung Circulation in Pulmonary Hypertension

This study is currently recruiting participants.
Verified July 2013 by Golden Jubilee National Hospital
Sponsor:
Collaborators:
NHS Lothian
Imperial College Healthcare NHS Trust
Information provided by (Responsible Party):
Golden Jubilee National Hospital
ClinicalTrials.gov Identifier:
NCT01457170
First received: October 20, 2011
Last updated: July 12, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
Pulmonary Arterial Hypertension
Heart Failure
Drug: Apelin
Drug: Saline (Placebo)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Investigating the Acute Pulmonary Vascular Haemodynamic Effects of Apelin in Pulmonary Hypertension

Resource links provided by NLM:


Further study details as provided by Golden Jubilee National Hospital:

Primary Outcome Measures:
  • Change in pulmonary vascular resistance [ Time Frame: 5,10,15 and 30 minutes after start of infusion ] [ Designated as safety issue: No ]
    We will measure the change in pulmonary vascular resistance after infusion of Apelin during right heart catheterisation


Secondary Outcome Measures:
  • Change in systemic vascular resistance [ Time Frame: 5,10,15 and 30 minutes after start of infusion ] [ Designated as safety issue: No ]
    We will measure the change in systemic vascular resistance during infusion of Apelin

  • Change in Cardiac Output [ Time Frame: 5,10,15 and 30 minutes after start of infusion ] [ Designated as safety issue: No ]
    We will measure the change in cardiac output after infusion of Apelin during right heart catheterisation.


Estimated Enrollment: 63
Study Start Date: January 2012
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apelin/Saline
Apelin infusion then crossover to Saline infusion
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.
Drug: 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.
Experimental: Saline/Apelin
Saline infusion then crossover to Apelin infusion
Drug: 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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01457170

Contacts
Contact: Andrew J Peacock, BSc MPhil MD +44 (0)141 951 5497 apeacock@udcf.gla.ac.uk
Contact: Lauren Brash, MBChB +44 (0)7738569980 laurenbrash@nhs.net

Locations
United Kingdom
Royal Infirmary Edinburgh Recruiting
Edinburgh, United Kingdom, EH16 4SA
Contact: David E Newby, BM, PhD, DM    +44 (0)131 242 6515    d.e.newby@ed.ac.uk   
Principal Investigator: David E Newby, BM, Phd, DM         
Sub-Investigator: Colin Stirrat, MB ChB         
Golden Jubilee National Hospital Recruiting
Glasgow, United Kingdom, G81 4HX
Contact: Andrew J Peacock, BSc MPhil MD    +44 (0)141 951 5497    apeacock@udcf.gla.ac.uk   
Contact: Lauren Brash, MB ChB    +44 (0)7738 569980    laurenbrash@nhs.net   
Sub-Investigator: Lauren Brash, MBChB         
Sub-Investigator: Martin K Johnson, MBChB, MD         
Sub-Investigator: David J Welsh, BSc, PhD         
Hammersmith Hospital Recruiting
London, United Kingdom, W12 0HS
Contact: Luke SG Howard, MA, MB BChir    +44 (0)20 83831317    l.howard@imperial.ac.uk   
Contact: Gareth Barnes, MB ChB    +44 (0)20 83831317    g.barnes@imperial.ac.uk   
Principal Investigator: Luke SG Howard, MA, MB BChir         
Sub-Investigator: Gareth Barnes, MBChB         
Sub-Investigator: Martin R Wilkins, MD, FRCP         
Sub-Investigator: Simon J Gibbs, MD, MB Bhir         
Sponsors and Collaborators
Golden Jubilee National Hospital
NHS Lothian
Imperial College Healthcare NHS Trust
Investigators
Principal Investigator: Andrew J Peacock, BSc MPhil MD National Health Service: Golden Jubilee National Hospital
  More Information

No publications provided

Responsible Party: Golden Jubilee National Hospital
ClinicalTrials.gov Identifier: NCT01457170     History of Changes
Other Study ID Numbers: 11/CARD/04
Study First Received: October 20, 2011
Last Updated: July 12, 2013
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: National Health Service

Keywords provided by Golden Jubilee National Hospital:
Pulmonary Hypertension
Heart Failure
Apelin
Haemodynamics
pulmonary vascular resistance
cardiac output

Additional relevant MeSH terms:
Hypertension, Pulmonary
Heart Failure
Hypertension
Lung Diseases
Respiratory Tract Diseases
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on April 15, 2014