Pulmonary Arterial HypertensionNCT01457170
Effects of Apelin on the Lung Circulation in Pulmonary Hypertension
A study testing Apelin in people with Pulmonary Arterial Hypertension and Heart Failure, run by Golden Jubilee National Hospital at 3 sites in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension, Heart Failure
- What is being tested?
- Apelin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Jan 2012to Jan 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- significant left ventricular dysfunction
- chronic lung disease (FEV1 < 60% or abnormal CT)
- chronic thromboembolic pulmonary hypertension
- HEART FAILURE
- obstructive coronary artery disease
- ALL SUBJECTS
Show all 16Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites, 3 recruiting
- Recruiting
Royal Infirmary Edinburgh
Edinburgh, EH16 4SA
David E Newby, BM, PhD, DM, +44 (0)131 242 6515, d.e.newby@ed.ac.uk
David E Newby, BM, Phd, DM
- Recruiting
Golden Jubilee National Hospital
Glasgow, G81 4HX
Andrew J Peacock, BSc MPhil MD, +44 (0)141 951 5497, apeacock@udcf.gla.ac.uk
Lauren Brash, MB ChB, +44 (0)7738 569980, laurenbrash@nhs.net
- Recruiting
Hammersmith Hospital
London, W12 0HS
Luke SG Howard, MA, MB BChir, +44 (0)20 83831317, l.howard@imperial.ac.uk
Gareth Barnes, MB ChB, +44 (0)20 83831317, g.barnes@imperial.ac.uk
About this study
Official title: Investigating the Acute Pulmonary Vascular Haemodynamic Effects of Apelin in Pulmonary Hypertension
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.
Read the 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
- Being tested
- Apelin, Saline (Placebo)
- Keywords
- Pulmonary Hypertension, Heart Failure, Apelin, Haemodynamics, pulmonary vascular resistance, cardiac output
- Medical subject headings
- Pulmonary Arterial Hypertension, Heart Failure, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApelinDrug
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)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 (Placebo)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.
ApelinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Apelin/Saline | Experimental | Apelin infusion then crossover to Saline infusion Receives: Drug: Apelin; Drug: Saline (Placebo) |
| Saline/Apelin | Experimental | Saline infusion then crossover to Apelin infusion Receives: Drug: Saline (Placebo); Drug: Apelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in pulmonary vascular resistance
We will measure the change in pulmonary vascular resistance after infusion of Apelin during right heart catheterisation
Measured: 5,10,15 and 30 minutes after start of infusion
Secondary outcomes (2)
Change in systemic vascular resistance
We will measure the change in systemic vascular resistance during infusion of Apelin
Measured: 5,10,15 and 30 minutes after start of infusion
Change in Cardiac Output
We will measure the change in cardiac output after infusion of Apelin during right heart catheterisation.
Measured: 5,10,15 and 30 minutes after start of infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2011 (estimated)
- Study startJan 2012
- Primary completionJan 2014 (estimated)
- Study completionJan 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 63 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Golden Jubilee National Hospital
- Sponsor type
- Other government
- Collaborators
- NHS Lothian, Imperial College Healthcare NHS Trust
- Responsible party
- Sponsor
- Investigators
- Andrew J Peacock, BSc MPhil MD, Principal investigator, National Health Service: Golden Jubilee National Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01457170
- Sponsor's protocol ID
- 11/CARD/04
- Status last verified
- Jul 2013
- First submitted
- 20 Oct 2011
- Last updated
- 15 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 29876530
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Acute Pulmonary Vascular Haemodynamic Effects of Apelin in Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT01457170
- Acronym / sponsor ID
- 11/CARD/04
- Conditions
- Pulmonary Arterial Hypertension, Heart Failure
- Keywords
- Pulmonary Hypertension, Heart Failure, Apelin, Haemodynamics, pulmonary vascular resistance, cardiac output
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 63 participants (estimated)
- Lead sponsor
- Golden Jubilee National HospitalOther government
- Collaborators
- NHS Lothian, Imperial College Healthcare NHS Trust
- Study start
- Jan 2012
- Primary completion
- Jan 2014 (estimated)
- Study completion
- Jan 2014 (estimated)
- First posted
- 21 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apelin/Saline | Experimental | Drug: Apelin, Drug: Saline (Placebo)Apelin infusion then crossover to Saline infusion |
| Saline/Apelin | Experimental | Drug: Saline (Placebo), Drug: ApelinSaline infusion then crossover to Apelin infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (16 listed)
- significant left ventricular dysfunction
- chronic lung disease (FEV1 < 60% or abnormal CT)
- chronic thromboembolic pulmonary hypertension
- HEART FAILURE
- obstructive coronary artery disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApelinDuring 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 | Apelin/Saline |
| 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/Saline |
| 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 | Saline/Apelin |
| ApelinDuring 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/Apelin |
Primary outcome
Change in pulmonary vascular resistance
Time frame: 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
2 secondary outcomes
Change in systemic vascular resistance
Time frame: 5,10,15 and 30 minutes after start of infusion
Change in Cardiac Output
Time frame: 5,10,15 and 30 minutes after start of infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2013.
- Derived from this study: PubMed 29876530Brash 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew J Peacock, BSc MPhil MD principal investigator
National Health Service: Golden Jubilee National Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Apelin in people with Pulmonary Arterial Hypertension and Heart Failure, run by Golden Jubilee National Hospital at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrew J Peacock, BSc MPhil MD (+44 (0)141 951 5497, apeacock@udcf.gla.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in pulmonary vascular resistance (time frame: 5,10,15 and 30 minutes after start of infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01457170, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2013.