Back to resultsEffects of Apelin on the Lung Circulation in Pulmonary Hypertension
Primary Purpose
Pulmonary Arterial Hypertension, Heart Failure
Status
Unknown status
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Apelin
Saline (Placebo)
Saline (Placebo)
Apelin
Sponsored by
About this trial
This is an interventional basic science trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary Hypertension, Heart Failure, Apelin, Haemodynamics, pulmonary vascular resistance, cardiac output
Eligibility 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
Sites / Locations
- Royal Infirmary EdinburghRecruiting
- Golden Jubilee National HospitalRecruiting
- Hammersmith HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Apelin/Saline
Saline/Apelin
Arm Description
Apelin infusion then crossover to Saline infusion
Saline infusion then crossover to Apelin infusion
Outcomes
Primary Outcome Measures
Change in pulmonary vascular resistance
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
We will measure the change in systemic vascular resistance during infusion of Apelin
Change in Cardiac Output
We will measure the change in cardiac output after infusion of Apelin during right heart catheterisation.
Full Information
NCT ID
NCT01457170
First Posted
October 20, 2011
Last Updated
July 12, 2013
Sponsor
Golden Jubilee National Hospital
Collaborators
NHS Lothian, Imperial College Healthcare NHS Trust
1. Study Identification
Unique Protocol Identification Number
NCT01457170
Brief Title
Effects of Apelin on the Lung Circulation in Pulmonary Hypertension
Official Title
Investigating the Acute Pulmonary Vascular Haemodynamic Effects of Apelin in Pulmonary Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Unknown status
Study Start Date
January 2012 (undefined)
Primary Completion Date
January 2014 (Anticipated)
Study Completion Date
January 2014 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Golden Jubilee National Hospital
Collaborators
NHS Lothian, Imperial College Healthcare NHS Trust
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension, Heart Failure
Keywords
Pulmonary Hypertension, Heart Failure, Apelin, Haemodynamics, pulmonary vascular resistance, cardiac output
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
63 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Apelin/Saline
Arm Type
Experimental
Arm Description
Apelin infusion then crossover to Saline infusion
Arm Title
Saline/Apelin
Arm Type
Experimental
Arm Description
Saline infusion then crossover to Apelin infusion
Intervention Type
Drug
Intervention Name(s)
Apelin
Intervention Description
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
Intervention Name(s)
Saline (Placebo)
Intervention Description
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
Intervention Name(s)
Saline (Placebo)
Intervention Description
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
Intervention Name(s)
Apelin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in pulmonary vascular resistance
Description
We will measure the change in pulmonary vascular resistance after infusion of Apelin during right heart catheterisation
Time Frame
5,10,15 and 30 minutes after start of infusion
Secondary Outcome Measure Information:
Title
Change in systemic vascular resistance
Description
We will measure the change in systemic vascular resistance during infusion of Apelin
Time Frame
5,10,15 and 30 minutes after start of infusion
Title
Change in Cardiac Output
Description
We will measure the change in cardiac output after infusion of Apelin during right heart catheterisation.
Time Frame
5,10,15 and 30 minutes after start of infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrew J Peacock, BSc MPhil MD
Phone
+44 (0)141 951 5497
Email
apeacock@udcf.gla.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Lauren Brash, MBChB
Phone
+44 (0)7738569980
Email
laurenbrash@nhs.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew J Peacock, BSc MPhil MD
Organizational Affiliation
National Health Service: Golden Jubilee National Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Infirmary Edinburgh
City
Edinburgh
ZIP/Postal Code
EH16 4SA
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David E Newby, BM, PhD, DM
Phone
+44 (0)131 242 6515
Email
d.e.newby@ed.ac.uk
First Name & Middle Initial & Last Name & Degree
David E Newby, BM, Phd, DM
First Name & Middle Initial & Last Name & Degree
Colin Stirrat, MB ChB
Facility Name
Golden Jubilee National Hospital
City
Glasgow
ZIP/Postal Code
G81 4HX
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew J Peacock, BSc MPhil MD
Phone
+44 (0)141 951 5497
Email
apeacock@udcf.gla.ac.uk
First Name & Middle Initial & Last Name & Degree
Lauren Brash, MB ChB
Phone
+44 (0)7738 569980
Email
laurenbrash@nhs.net
First Name & Middle Initial & Last Name & Degree
Lauren Brash, MBChB
First Name & Middle Initial & Last Name & Degree
Martin K Johnson, MBChB, MD
First Name & Middle Initial & Last Name & Degree
David J Welsh, BSc, PhD
Facility Name
Hammersmith Hospital
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luke SG Howard, MA, MB BChir
Phone
+44 (0)20 83831317
Email
l.howard@imperial.ac.uk
First Name & Middle Initial & Last Name & Degree
Gareth Barnes, MB ChB
Phone
+44 (0)20 83831317
Email
g.barnes@imperial.ac.uk
First Name & Middle Initial & Last Name & Degree
Luke SG Howard, MA, MB BChir
First Name & Middle Initial & Last Name & Degree
Gareth Barnes, MBChB
First Name & Middle Initial & Last Name & Degree
Martin R Wilkins, MD, FRCP
First Name & Middle Initial & Last Name & Degree
Simon J Gibbs, MD, MB Bhir
12. IPD Sharing Statement
Citations:
PubMed Identifier
29876530
Citation
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.
Results Reference
derived
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Effects of Apelin on the Lung Circulation in Pulmonary Hypertension
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