Angiogenesis and Fibrosis in Aortic Stenosis

NCT01837160 | Completed DMC

• 2 other identifiers: 2012/R/CAR/23FS/12/84/29814
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Aortic Stenosis; Fibrosis; Neovascularization, Pathologic

Keywords

Angiogenesis; Fibrosis; Aortic Stenosis; Imaging; CT-PET; PET-CT; Cardiac MRI

Outcome Measures

Primary Outcomes (2)

• The mean and maximum standardised uptake values (SUV) of fluciclatide for the myocardium and its correlation with the severity of aortic stenosis determined echocardiographically.

  1 - 2 years

• 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.

  1 - 2 years

Secondary Outcomes (2)

• The mean and maximum standardised uptake values (SUV) of fluciclatide in the aortic valve in patients with aortic stenosis

  1 year

• The mean and maximum standardised uptake values (SUV) of fluciclatide in concomitant aortic atheroma

  1 year

Study Arms (5)

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; Radiation: CT-PET scan; Procedure: Echocardiogram; Radiation: CT-coronary angiogram scan

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; Radiation: CT-PET scan; Procedure: Echocardiogram; Radiation: CT-coronary angiogram scan

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; Radiation: CT-PET scan; Procedure: Echocardiogram; Radiation: CT-coronary angiogram scan

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; Radiation: CT-PET scan; Procedure: Echocardiogram; Radiation: CT-coronary angiogram scan

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; Radiation: CT-PET scan; Procedure: Echocardiogram; Radiation: CT-coronary angiogram scan; Procedure: Aortic Valve Replacement

Interventions

Cardiac MRI scan PROCEDURE

Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping.

Healthy Volunteers; Mild Aortic Stenosis (n=10); Moderate Aortic Stenosis (n=10); Severe Aortic Stenosis for AVR (n=10); Severe aortic Stenosis (n=10)

CT-PET scan RADIATION

Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer.

Healthy Volunteers; Mild Aortic Stenosis (n=10); Moderate Aortic Stenosis (n=10); Severe Aortic Stenosis for AVR (n=10); Severe aortic Stenosis (n=10)

Echocardiogram PROCEDURE

Echocardiography.

Healthy Volunteers; Mild Aortic Stenosis (n=10); Moderate Aortic Stenosis (n=10); Severe Aortic Stenosis for AVR (n=10); Severe aortic Stenosis (n=10)

CT-coronary angiogram scan RADIATION

CT-coronary angiogram following CT-PET scan. Standard protocol.

Healthy Volunteers; Mild Aortic Stenosis (n=10); Moderate Aortic Stenosis (n=10); Severe Aortic Stenosis for AVR (n=10); Severe aortic Stenosis (n=10)

Aortic Valve Replacement PROCEDURE

For AVR (already scheduled prior to enrollment)

Also known as: AVR

Severe Aortic Stenosis for AVR (n=10)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

50 patients in total, recruited from Cardiology Outpatient Clinics

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Edinburgh: lead

Study Sites (1)

University of Edinburgh

Edinburgh, Lothian, EH16 4TJ, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

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

MeSH Terms

Conditions

Aortic Valve Stenosis; Fibrosis; Neovascularization, Pathologic

Interventions

Transcatheter Aortic Valve Replacement

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Metaplasia

Intervention Hierarchy (Ancestors)

Heart Valve Prosthesis Implantation; Cardiac Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Prosthesis Implantation; Thoracic Surgical Procedures

Study Officials

• David E Newby, MBChB PhD

  University of Edinburgh

  STUDY DIRECTOR

• William Sa Jenkins, MBChB MRCP

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2013
• First Posted: April 23, 2013
• Study Start: April 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: August 30, 2016

Record last verified: 2015-03

Locations

GB (1)