Effects of Apelin on the Lung Circulation in Pulmonary Hypertension

NCT ID: NCT01457170

Last Updated: 2013-07-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2014-01-31

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.

Conditions

Pulmonary Arterial Hypertension; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Apelin/Saline

Apelin infusion then crossover to Saline infusion

Group Type: EXPERIMENTAL

Apelin

Intervention Type: DRUG

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)

Intervention Type: DRUG

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/Apelin

Saline infusion then crossover to Apelin infusion

Group Type: EXPERIMENTAL

Saline (Placebo)

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• 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

• mean pulmonary artery pressure < 25 mmHg
• tricuspid regurgitant velocity < 2.5 m/s

Exclusion Criteria

• significant left ventricular dysfunction
• chronic lung disease (FEV1 < 60% or abnormal CT)
• chronic thromboembolic pulmonary hypertension

HEART FAILURE

• obstructive coronary artery disease

ALL SUBJECTS

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

NHS Lothian

OTHER_GOV

Sponsor Role: collaborator

Imperial College Healthcare NHS Trust

OTHER

Sponsor Role: collaborator

Golden Jubilee National Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew J Peacock, BSc MPhil MD

Role: PRINCIPAL_INVESTIGATOR

National Health Service: Golden Jubilee National Hospital

Locations

Royal Infirmary Edinburgh

Edinburgh, , United Kingdom

Site Status: RECRUITING

Golden Jubilee National Hospital

Glasgow, , United Kingdom

Site Status: RECRUITING

Hammersmith Hospital

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Andrew J Peacock, BSc MPhil MD

Role: CONTACT

apeacock@udcf.gla.ac.uk

+44 (0)141 951 5497

Lauren Brash, MBChB

Role: CONTACT

laurenbrash@nhs.net

+44 (0)7738569980

Facility Contacts

David E Newby, BM, PhD, DM

Role: primary

d.e.newby@ed.ac.uk

+44 (0)131 242 6515

Andrew J Peacock, BSc MPhil MD

Role: primary

apeacock@udcf.gla.ac.uk

+44 (0)141 951 5497

Lauren Brash, MB ChB

Role: backup

laurenbrash@nhs.net

+44 (0)7738 569980

Luke SG Howard, MA, MB BChir

Role: primary

l.howard@imperial.ac.uk

+44 (0)20 83831317

Gareth Barnes, MB ChB

Role: backup

g.barnes@imperial.ac.uk

+44 (0)20 83831317

References

Brash L, Barnes GD, Brewis MJ, Church AC, Gibbs SJ, Howard LSGE, Jayasekera G, Johnson MK, McGlinchey N, Onorato J, Simpson J, Stirrat C, Thomson S, Watson G, Wilkins MR, Xu C, Welsh DJ, Newby DE, Peacock AJ. Short-Term Hemodynamic Effects of Apelin in Patients With Pulmonary Arterial Hypertension. JACC Basic Transl Sci. 2018 Mar 28;3(2):176-186. doi: 10.1016/j.jacbts.2018.01.013. eCollection 2018 Apr.

Reference Type: DERIVED

PMID: 29876530 (View on PubMed)

Other Identifiers

11/CARD/04

Identifier Type: -

Identifier Source: org_study_id