Angiogenesis and Fibrosis in Aortic Stenosis

This study is not yet open for participant recruitment.
Verified April 2013 by University of Edinburgh
Sponsor:
Information provided by (Responsible Party):
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT01837160
First received: March 14, 2013
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

Angiogenesis and fibrosis lie at the heart of a number of fundamental processes responsible for cardiovascular disease. In this proposal, the investigators intend to build upon a highly successful programme of studies exploring the cardiovascular applications of positron emission tomography. Specifically, the investigators will explore the potential role of a novel radiotracer, 18F-fluciclatide, which is a highly selective ligand for the αvβ3 and αvβ5 integrin receptors that are up regulated during angiogenesis, and tissue fibrosis and remodelling. This tracer has been successfully used to assess angiogenesis in metastatic tumours and its uptake is suppressed by anti-angiogenic therapies. The investigators here propose to describe the pattern of uptake of 18F-fluciclatide in cardiovascular diseases, specifically aortic stenosis and aortic atherosclerosis. The investigators will correlate 18F-fluciclatide uptake with in vivo measures of angiogenesis and fibrosis as well as ex vivo histological characterisation of tissue. If successful, this novel radiotracer could provide an extremely important non-invasive method of assessing in vivo angiogenesis, plaque vulnerability, and tissue remodelling as well as potential applications in developing stem cell therapies.


Condition Intervention
Aortic Stenosis
Fibrosis
Neovascularization, Pathologic
Procedure: Cardiac MRI scan
Radiation: CT-PET scan
Procedure: Echocardiogram
Radiation: CT-coronary angiogram scan
Procedure: Aortic Valve Replacement

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Identification of In Vivo Angiogenesis and Fibrosis in Aortic Stenosis Using Positron Emission Tomography

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • The mean and maximum standardised uptake values (SUV) of fluciclatide for the myocardium and its correlation with the severity of aortic stenosis determined echocardiographically. [ Time Frame: 1 - 2 years ] [ Designated as safety issue: No ]
  • The mean and maximum standardised uptake values (SUV) of fluciclatide for the myocardium and its correlation with the volume of myocardial fibrosis on magnetic resonance scanning. [ Time Frame: 1 - 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The mean and maximum standardised uptake values (SUV) of fluciclatide in the aortic valve in patients with aortic stenosis [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The mean and maximum standardised uptake values (SUV) of fluciclatide in concomitant aortic atheroma [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Blood samples will be taken, and the serum frozen and stored for further analysis pending ethical approval.


Estimated Enrollment: 50
Study Start Date: April 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Healthy Volunteers

10 patients with normal echocardiogram studies and no history of ischaemic heart disease.

Patients to recieve CT-PET with fluciclatide, cardiac MRI scan, CT-coronary angiogram and echocardiogram.

Procedure: Cardiac MRI scan
Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping.
Radiation: CT-PET scan
Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer.
Procedure: Echocardiogram
Echocardiography.
Radiation: CT-coronary angiogram scan
CT-coronary angiogram following CT-PET scan. Standard protocol.
Moderate Aortic Stenosis (n=10)

Patients with moderate aortic stenosis. Patients are to recieve Cardiac MRI, CT-PET scan, echocardiography and CT-coronary angiogram scan at baseline.

They will undergo repeat cardiac MRI scan and echocardiogram at 12 - 24 months.

Procedure: Cardiac MRI scan
Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping.
Radiation: CT-PET scan
Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer.
Procedure: Echocardiogram
Echocardiography.
Radiation: CT-coronary angiogram scan
CT-coronary angiogram following CT-PET scan. Standard protocol.
Mild Aortic Stenosis (n=10)

Patients with mild aortic stenosis. Patients are to recieve Cardiac MRI, CT-PET scan, echocardiography and CT-coronary angiogram scan at baseline.

They will undergo repeat cardiac MRI scan and echocardiogram at 12 - 24 months.

Procedure: Cardiac MRI scan
Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping.
Radiation: CT-PET scan
Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer.
Procedure: Echocardiogram
Echocardiography.
Radiation: CT-coronary angiogram scan
CT-coronary angiogram following CT-PET scan. Standard protocol.
Severe aortic Stenosis (n=10)

Patients with severe aortic stenosis. Patients are to recieve Cardiac MRI, CT-PET scan, echocardiography and CT-coronary angiogram scan at baseline.

They will undergo repeat cardiac MRI scan and echocardiogram at 12 - 24 months.

Procedure: Cardiac MRI scan
Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping.
Radiation: CT-PET scan
Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer.
Procedure: Echocardiogram
Echocardiography.
Radiation: CT-coronary angiogram scan
CT-coronary angiogram following CT-PET scan. Standard protocol.
Severe Aortic Stenosis for AVR (n=10)

Patients with severe aortic stenosis proceeding to aortic valve replacement. Patients are to recieve Cardiac MRI, CT-PET scan, echocardiography and CT-coronary angiogram scan at baseline.

They will undergo a repeat CT-PET scan 3 months after the operation.

They will undergo repeat cardiac MRI scan and echocardiogram at 12 months after the operation.

Procedure: Cardiac MRI scan
Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping.
Radiation: CT-PET scan
Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer.
Procedure: Echocardiogram
Echocardiography.
Radiation: CT-coronary angiogram scan
CT-coronary angiogram following CT-PET scan. Standard protocol.
Procedure: Aortic Valve Replacement
For AVR (already scheduled prior to enrollment)
Other Name: AVR

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

50 patients in total, recruited from Cardiology Outpatient Clinics

Criteria

Inclusion Criteria

  • asymptomatic mild (peak valve velocity of 2-5-3.0 m/s; n=10), moderate (peak valve velocity of 3.0-4.0 m/s; n=10) or severe aortic stenosis (peak valve velocity of >4.0 m/s; n=10) and 10 patients with severe aortic stenosis proceeding to aortic valve replacement.
  • Healthy control subjects (n=10) will have no past medical history of ischaemic heart disease or valvular heart disease and have a structurally normal heart on echocardiography.

Exclusion Criteria:

  • Atrial fibrillation
  • Hepatic failure (Childs-Pugh grade B or C)
  • Renal failure (estimated glomerular filtration rate <25 mL/min)
  • Women of child-bearing potential
  • Contraindication to magnetic resonance imaging
  • Inability to undergo scanning
  • Ochronosis and those with any form of collagen-vascular disease.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01837160

Contacts
Contact: William SA Jenkins, MBChB MRCP 01312421000 ext 26428 williamjenkins@doctors.net.uk
Contact: David E Newby, MBChB PhD 01312421000 d.e.newby@nhs.net

Locations
United Kingdom
University of Edinburgh Not yet recruiting
Edinburgh, Lothian, United Kingdom, EH16 4TJ
Sponsors and Collaborators
University of Edinburgh
Investigators
Study Director: David E Newby, MBChB PhD University of Edinburgh
Principal Investigator: William Sa Jenkins, MBChB MRCP University of Edinburgh
  More Information

No publications provided

Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT01837160     History of Changes
Other Study ID Numbers: 2012/R/CAR/23, FS/12/84/29814
Study First Received: March 14, 2013
Last Updated: April 17, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:
Angiogenesis
Fibrosis
Aortic Stenosis
Imaging
CT-PET
PET-CT
Cardiac MRI

Additional relevant MeSH terms:
Aortic Valve Stenosis
Constriction, Pathologic
Fibrosis
Neovascularization, Pathologic
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Pathological Conditions, Anatomical
Pathologic Processes
Metaplasia

ClinicalTrials.gov processed this record on April 23, 2014