Aortic StenosisNCT01358513
Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis
An observational study of Aortic Stenosis, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
The aortic valve is the main outlet valve from the heart. This valve can become diseased and narrowed when it needs to be replaced with an artificial valve. Currently, this is the commonest reason for someone to undergo a heart valve operation in the UK. Read more about this study
- Who is it for?
- Ages 50 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Aortic Stenosis
- How many people
- 121 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2010to Jul 2015
- Phase
- Observational
- 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 50 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The investigators will recruit 168 patients: 24 control patients, 24 mild, 48 moderate and 48 severe aortic stenosis
Who may be able to join
- Age > 50 years
Who cannot join
- Age < 50 years
- Life expectancy < 2 years
- Insulin dependent diabetes mellitus
- Connective Tissue disorders
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Centre for Cardiovascular Sciences, University of Edinburgh
Edinburgh, Scotland, EH16 4SE
About this study
Official title: An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis
The aortic valve is the main outlet valve from the heart. This valve can become diseased and narrowed when it needs to be replaced with an artificial valve. Currently, this is the commonest reason for someone to undergo a heart valve operation in the UK. Unfortunately, there are no medical treatments that can prevent or delay the progression of this disease process. Here, the investigators propose to use new state-of-the-art imaging techniques to better understand the disease process so that the investigators can effectively design and assess potential new treatments. The ultimate aim is to stop this disease before patients need to have surgery. In addition the investigators believe this technique will allow us to predict the rate of progression of the disease
Read the detailed description
Aortic stenosis is the commonest valvular heart disease in the western world and is the leading indication for valve surgery. Histological studies have suggested similarities with atherosclerosis including inflammation, lipid deposition, increased macrophage activity and calcification. However, recent randomised controlled trials have failed to demonstrate a reduction in the rate of disease progression with statin therapy and the investigators believe there is now a need to re-evaluate the underlying factors involved in the initiation and progression of aortic stenosis. The investigators propose to assess the role of inflammation and calcification in the pathogenesis and progression of aortic stenosis by using positron emission tomography with [18F]-fluorodeoxyglucose and [18F-]-fluoride in patients with a range of aortic valve disease. The investigators hypothesise that increasing severity of valvular inflammation and calcification will correlate with disease severity and rate of disease progression. This work will lay the foundation for the subsequent application of interventions targeted at inflammation and calcification.
- Conditions
- Aortic Stenosis
- Keywords
- Positron Emission Tomography, Inflammation, Calcification
- Medical subject headings
- Aortic Valve Stenosis, Inflammation, Calcinosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Control Patients | Patients with normal aortic valves | |
| Aortic sclerosis | To undergo PET imaging and follow up with CT and echo for 2 years | |
| Mild Aortic stenosis | To undergo PET imaging and follow up with CT and echo for 2 years | |
| Moderate Aortic stenosis | To undergo PET imaging and follow up with CT and echo for 2 years | |
| Severe aortic stenosis | To undergo PET imaging and follow up with CT and echo for 2 years |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aortic Valve Peak Velocity
We beleive NaF and FDG uptake in the valve will predict rate of progression of the disease. Disease severity will be measured by the aortic valve peak velocity
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2011 (estimated)
- Study startJul 2010
- Primary completionJul 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian, British Heart Foundation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01358513
- Sponsor's protocol ID
- RING OF FIRE
- Status last verified
- Jan 2015
- First submitted
- 19 May 2011
- Last updated
- 25 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fletcher AJ, Tew YY, Tzolos E, Joshi SS, Kaczynski J, Nash J, Debono S, Lembo M, Kwiecinski J, Bing R, Syed MBJ, Doris MK, van Beek EJR, Moss AJ, Jenkins WS, Walker NL, Joshi NV, Pawade TA, Adamson PD, Whiteley WN, Wardlaw JM, Slomka PJ, Williams MC, Newby DE, Dweck MR. Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease. JACC Cardiovasc Imaging. 2022 Jul;15(7):1274-1288. doi: 10.1016/j.jcmg.2021.12.013. Epub 2022 Feb 16.
PubMed 35183477Pawade T, Clavel MA, Tribouilloy C, Dreyfus J, Mathieu T, Tastet L, Renard C, Gun M, Jenkins WSA, Macron L, Sechrist JW, Lacomis JM, Nguyen V, Galian Gay L, Cuellar Calabria H, Ntalas I, Cartlidge TRG, Prendergast B, Rajani R, Evangelista A, Cavalcante JL, Newby DE, Pibarot P, Messika Zeitoun D, Dweck MR. Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis. Circ Cardiovasc Imaging. 2018 Mar;11(3):e007146. doi: 10.1161/CIRCIMAGING.117.007146.
PubMed 29555836Dweck MR, Jenkins WS, Vesey AT, Pringle MA, Chin CW, Malley TS, Cowie WJ, Tsampasian V, Richardson H, Fletcher A, Wallace WA, Pessotto R, van Beek EJ, Boon NA, Rudd JH, Newby DE. 18F-sodium fluoride uptake is a marker of active calcification and disease progression in patients with aortic stenosis. Circ Cardiovasc Imaging. 2014 Mar;7(2):371-8. doi: 10.1161/CIRCIMAGING.113.001508. Epub 2014 Feb 7.
PubMed 24508669Dweck MR, Khaw HJ, Sng GK, Luo EL, Baird A, Williams MC, Makiello P, Mirsadraee S, Joshi NV, van Beek EJ, Boon NA, Rudd JH, Newby DE. Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation? Eur Heart J. 2013 Jun;34(21):1567-74. doi: 10.1093/eurheartj/eht034. Epub 2013 Feb 7.
PubMed 23391586Dweck MR, Chow MW, Joshi NV, Williams MC, Jones C, Fletcher AM, Richardson H, White A, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012 Apr 24;59(17):1539-48. doi: 10.1016/j.jacc.2011.12.037.
PubMed 22516444Dweck MR, Jones C, Joshi NV, Fletcher AM, Richardson H, White A, Marsden M, Pessotto R, Clark JC, Wallace WA, Salter DM, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation. 2012 Jan 3;125(1):76-86. doi: 10.1161/CIRCULATIONAHA.111.051052. Epub 2011 Nov 16.
PubMed 22090163
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis
- ClinicalTrials.gov ID
- NCT01358513
- Acronym / sponsor ID
- RING OF FIRE
- Conditions
- Aortic Stenosis
- Keywords
- Positron Emission Tomography, Inflammation, Calcification
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian, British Heart Foundation
- Study start
- Jul 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 23 May 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 aortic valve is the main outlet valve from the heart. This valve can become diseased and narrowed when it needs to be replaced with an artificial valve. Currently, this is the commonest reason for someone to undergo a heart valve operation in the UK. Unfortunately, there are no medical treatments that can prevent or delay the progression of this disease process. Here, the investigators propose to use new state-of-the-art imaging techniques to better understand the disease process so that the investigators can effectively design and assess potential new treatments. The ultimate aim is to stop this disease before patients need to have surgery. In addition the investigators believe this technique will allow us to predict the rate of progression of the disease
Detailed description
Aortic stenosis is the commonest valvular heart disease in the western world and is the leading indication for valve surgery. Histological studies have suggested similarities with atherosclerosis including inflammation, lipid deposition, increased macrophage activity and calcification. However, recent randomised controlled trials have failed to demonstrate a reduction in the rate of disease progression with statin therapy and the investigators believe there is now a need to re-evaluate the underlying factors involved in the initiation and progression of aortic stenosis. The investigators propose to assess the role of inflammation and calcification in the pathogenesis and progression of aortic stenosis by using positron emission tomography with [18F]-fluorodeoxyglucose and [18F-]-fluoride in patients with a range of aortic valve disease. The investigators hypothesise that increasing severity of valvular inflammation and calcification will correlate with disease severity and rate of disease progression. This work will lay the foundation for the subsequent application of interventions targeted at inflammation and calcification.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Control Patients | – | –Patients with normal aortic valves |
| Aortic sclerosis | – | –To undergo PET imaging and follow up with CT and echo for 2 years |
| Mild Aortic stenosis | – | –To undergo PET imaging and follow up with CT and echo for 2 years |
| Moderate Aortic stenosis | – | –To undergo PET imaging and follow up with CT and echo for 2 years |
| Severe aortic stenosis | – | –To undergo PET imaging and follow up with CT and echo for 2 years |
Who may qualify
- Ages
- 50 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The investigators will recruit 168 patients: 24 control patients, 24 mild, 48 moderate and 48 severe aortic stenosis
Key inclusion criteria (1 listed)
- Age > 50 years
Key exclusion criteria (4 listed)
- Age < 50 years
- Life expectancy < 2 years
- Insulin dependent diabetes mellitus
- Connective Tissue disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Aortic Valve Peak Velocity
Time frame: 2 years
We beleive NaF and FDG uptake in the valve will predict rate of progression of the disease. Disease severity will be measured by the aortic valve peak velocity
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2018.
- Derived from this study: PubMed 35183477Fletcher AJ, Tew YY, Tzolos E, Joshi SS, Kaczynski J, Nash J, Debono S, Lembo M, Kwiecinski J, Bing R, Syed MBJ, Doris MK, van Beek EJR, Moss AJ, Jenkins WS, Walker NL, Joshi NV, Pawade TA, Adamson PD, Whiteley WN, Wardlaw JM, Slomka PJ, Williams MC, Newby DE, Dweck MR. Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease. JACC Cardiovasc Imaging. 2022 Jul;15(7):1274-1288. doi: 10.1016/j.jcmg.2021.12.013. Epub 2022 Feb 16.
- Derived from this study: PubMed 29555836Pawade T, Clavel MA, Tribouilloy C, Dreyfus J, Mathieu T, Tastet L, Renard C, Gun M, Jenkins WSA, Macron L, Sechrist JW, Lacomis JM, Nguyen V, Galian Gay L, Cuellar Calabria H, Ntalas I, Cartlidge TRG, Prendergast B, Rajani R, Evangelista A, Cavalcante JL, Newby DE, Pibarot P, Messika Zeitoun D, Dweck MR. Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis. Circ Cardiovasc Imaging. 2018 Mar;11(3):e007146. doi: 10.1161/CIRCIMAGING.117.007146.
- Derived from this study: PubMed 24508669Dweck MR, Jenkins WS, Vesey AT, Pringle MA, Chin CW, Malley TS, Cowie WJ, Tsampasian V, Richardson H, Fletcher A, Wallace WA, Pessotto R, van Beek EJ, Boon NA, Rudd JH, Newby DE. 18F-sodium fluoride uptake is a marker of active calcification and disease progression in patients with aortic stenosis. Circ Cardiovasc Imaging. 2014 Mar;7(2):371-8. doi: 10.1161/CIRCIMAGING.113.001508. Epub 2014 Feb 7.
- Derived from this study: PubMed 23391586Dweck MR, Khaw HJ, Sng GK, Luo EL, Baird A, Williams MC, Makiello P, Mirsadraee S, Joshi NV, van Beek EJ, Boon NA, Rudd JH, Newby DE. Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation? Eur Heart J. 2013 Jun;34(21):1567-74. doi: 10.1093/eurheartj/eht034. Epub 2013 Feb 7.
- Derived from this study: PubMed 22516444Dweck MR, Chow MW, Joshi NV, Williams MC, Jones C, Fletcher AM, Richardson H, White A, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012 Apr 24;59(17):1539-48. doi: 10.1016/j.jacc.2011.12.037.
- Derived from this study: PubMed 22090163Dweck MR, Jones C, Joshi NV, Fletcher AM, Richardson H, White A, Marsden M, Pessotto R, Clark JC, Wallace WA, Salter DM, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation. 2012 Jan 3;125(1):76-86. doi: 10.1161/CIRCULATIONAHA.111.051052. Epub 2011 Nov 16.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aortic Stenosis, run by University of Edinburgh at 1 site 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 1 inclusion and 4 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: finished, as of the sponsor's last update on 25 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aortic Valve Peak Velocity (time frame: 2 years). 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 NCT01358513, which also lists 6 linked publications.
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 25 Jun 2018.