Unstable AnginaNCT00484406
MMP Polymorphisms and Acute Coronary Syndromes
An observational study of Unstable Angina, run by University of Trieste at 2 sites in Italy.
Trial summary
Some Matrix Metalloproteases, proteases degrading the extracellular matrix, play a relevant role in structure and stability of atherosclerotic plaques. Atherosclerotic plaques triggering acute coronary syndromes show increased expression of MMP-1, MMP-3 and MMP-9. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unstable Angina
- How many people
- Not given
- Where
- 2 sitesItaly
- Study dates
- Feb 2005to May 2007
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- non ST elevation acute coronary syndrome (NSTE ACS)
Who cannot join
- STE acute myocardial infarction
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Azienda per i Servizi Sanitari n.6 "FRIULI OCCIDENTALE"
Pordenone, Pordenone
Clinica Medica - University of Trieste
Trieste, Trieste, 34149
About this study
Official title: Matrix Metalloproteinase Genetic Polymorphisms and Outcome of Non-ST Elevated Acute Coronary Syndromes
Some Matrix Metalloproteases, proteases degrading the extracellular matrix, play a relevant role in structure and stability of atherosclerotic plaques. Atherosclerotic plaques triggering acute coronary syndromes show increased expression of MMP-1, MMP-3 and MMP-9. Regulation of these MMPs is plaid by genetic polymorphisms, G+/G- at -1563 for MMP-1, 4A/5A- at -1612 for MMP-3, and a microsatellite (13-27 CA repeats around -90) for MMP-9.
It is conceivable that these polymorphisms correlate with the clinical outcome of acute coronary syndromes, particularly with those without ST segment Elevation (NSTEACS).
Read the detailed description
Non-ST elevation acute coronary syndrome (NSTEACS) is a syndrome encompassing a spectrum of clinical manifestations between ischemic heart disease and acute myocardial infarction. It represents an important cause of morbidity and hospitalization in western countries: its incidence is estimated around 2/1000 subjects/year and about 10% of patients with acute coronary syndrome develop an acute myocardial infarction within 6 months. Another reason of concern is that patients require an invasive treatment, usually PTCA or CABG. ACS encompasses features of both an inflammatory and thrombotic disease; their abnormalities could be critical for evolution and complication of acute coronary syndrome.
Many inflammatory and coagulation indicators have been investigated, although the critical factors responsible for complications in NSTEACS remain elusive.
Matrix remodeling and consequent erosion or fissuration of the unstable plaque is supposed to be a key step of the development of acute coronary syndromes.
Neutral matrix metalloproteinases 1, 3 and 9 have been demonstrated to be actively produced in atherosclerotic tissue, compared to unaffected arteries. Mechanisms responsible for such increased expression might be related to inflammation, but also genetic regulation could account for an increased expression leading to a different clinical outcome of the syndrome.
Genetic polymorphisms are described for all three MMPs involved in ACS. MMP-1 insertion of a G in position creates an ets binding site that induces an eight times increase of the synthesis rate. For MMP-3 (stromelysin) polymorphism, a deletion of an A (adenosine) in position -1171 doubles the transcription activity and has been recently associated with acute myocardial infarction and progression of coronary stenosis. In MMP-9 a more complex polymorphism involves a microsatellite (AC) repeat in position -90 to -131. The mechanism leading to increased MMP-9 expression is probably related to the transition to Z-DNA within the microsatellite, which eases transcription. In vitro studies show that the longer the tandem repeats sequence, the higher the transcription.
No studies on metalloproteinase polymorphism in NSTEACS have been carried out, so far.
This study has been planned to assess if patients admitted to the hospital for NSTEACS could be associated to a different in hospital clinical outcome according to the genetic polymorphism of these proteases.
- Conditions
- Unstable Angina
- Keywords
- Matrix Metalloproteinases, Atherosclerosis, Genetic polymorphism, Acute coronary syndromes
- Medical subject headings
- Angina, Unstable, Atherosclerosis, Acute Coronary Syndrome
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2007 (estimated)
- Study startFeb 2005
- Study completionMay 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Unstable AnginaStudies 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
- Observational
- Observational model
- Defined population
- Time perspective
- Prospective
Sponsor and investigators
- Lead sponsor
- University of Trieste
- Sponsor type
- University, hospital or other
- Investigators
- Nicola FIOTTI, MD, Principal investigator, University of Trieste, ITALYCarlo Giansante, MD, Study chair, University of Trieste, ITALY
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00484406
- Sponsor's protocol ID
- FT-05-CG-201040106
- Status last verified
- May 2007
- First submitted
- 7 Jun 2007
- Last updated
- 8 Jun 2007
- Results posted
- No
- Data monitoring committee
- No
Publications
Fiotti N, Altamura N, Fisicaro M, Carraro N, Uxa L, Grassi G, Torelli L, Gobbato R, Guarnieri G, Baxter BT, Giansante C. MMP-9 microsatellite polymorphism and susceptibility to carotid arteries atherosclerosis. Arterioscler Thromb Vasc Biol. 2006 Jun;26(6):1330-6. doi: 10.1161/01.ATV.0000219233.31702.c9. Epub 2006 Mar 30.
PubMed 16574900Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994 Dec;94(6):2493-503. doi: 10.1172/JCI117619.
PubMed 7989608Pollanen PJ, Lehtimaki T, Mikkelsson J, Ilveskoski E, Kunnas T, Perola M, Penttila A, Mattila KM, Nikkari ST, Syrjakoski K, Karhunen PJ. Matrix metalloproteinase3 and 9 gene promoter polymorphisms: joint action of two loci as a risk factor for coronary artery complicated plaques. Atherosclerosis. 2005 May;180(1):73-8. doi: 10.1016/j.atherosclerosis.2004.10.041. Epub 2004 Dec 18.
PubMed 15823277Terashima M, Akita H, Kanazawa K, Inoue N, Yamada S, Ito K, Matsuda Y, Takai E, Iwai C, Kurogane H, Yoshida Y, Yokoyama M. Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction. Circulation. 1999 Jun 1;99(21):2717-9. doi: 10.1161/01.cir.99.21.2717.
PubMed 10351963Fiotti N, Moretti ME, Bussani R, Altamura N, Zamolo F, Gerloni R, Ukovich L, Ober E, Silvestri F, Grassi G, Adovasio R, Giansante C. Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase functional polymorphisms. Atherosclerosis. 2011 Mar;215(1):153-9. doi: 10.1016/j.atherosclerosis.2010.12.010. Epub 2010 Dec 21.
PubMed 21232745
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Matrix Metalloproteinase Genetic Polymorphisms and Outcome of Non-ST Elevated Acute Coronary Syndromes
- ClinicalTrials.gov ID
- NCT00484406
- Acronym / sponsor ID
- FT-05-CG-201040106
- Conditions
- Unstable Angina
- Keywords
- Matrix Metalloproteinases, Atherosclerosis, Genetic polymorphism, Acute coronary syndromes
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- University of TriesteUniversity, hospital or other
- Study start
- Feb 2005
- Study completion
- May 2007 (actual)
- First posted
- 8 Jun 2007 (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.
Some Matrix Metalloproteases, proteases degrading the extracellular matrix, play a relevant role in structure and stability of atherosclerotic plaques. Atherosclerotic plaques triggering acute coronary syndromes show increased expression of MMP-1, MMP-3 and MMP-9. Regulation of these MMPs is plaid by genetic polymorphisms, G+/G- at -1563 for MMP-1, 4A/5A- at -1612 for MMP-3, and a microsatellite (13-27 CA repeats around -90) for MMP-9.
It is conceivable that these polymorphisms correlate with the clinical outcome of acute coronary syndromes, particularly with those without ST segment Elevation (NSTEACS).
Detailed description
Non-ST elevation acute coronary syndrome (NSTEACS) is a syndrome encompassing a spectrum of clinical manifestations between ischemic heart disease and acute myocardial infarction. It represents an important cause of morbidity and hospitalization in western countries: its incidence is estimated around 2/1000 subjects/year and about 10% of patients with acute coronary syndrome develop an acute myocardial infarction within 6 months. Another reason of concern is that patients require an invasive treatment, usually PTCA or CABG. ACS encompasses features of both an inflammatory and thrombotic disease; their abnormalities could be critical for evolution and complication of acute coronary syndrome.
Many inflammatory and coagulation indicators have been investigated, although the critical factors responsible for complications in NSTEACS remain elusive.
Matrix remodeling and consequent erosion or fissuration of the unstable plaque is supposed to be a key step of the development of acute coronary syndromes.
Neutral matrix metalloproteinases 1, 3 and 9 have been demonstrated to be actively produced in atherosclerotic tissue, compared to unaffected arteries. Mechanisms responsible for such increased expression might be related to inflammation, but also genetic regulation could account for an increased expression leading to a different clinical outcome of the syndrome.
Genetic polymorphisms are described for all three MMPs involved in ACS. MMP-1 insertion of a G in position creates an ets binding site that induces an eight times increase of the synthesis rate. For MMP-3 (stromelysin) polymorphism, a deletion of an A (adenosine) in position -1171 doubles the transcription activity and has been recently associated with acute myocardial infarction and progression of coronary stenosis. In MMP-9 a more complex polymorphism involves a microsatellite (AC) repeat in position -90 to -131. The mechanism leading to increased MMP-9 expression is probably related to the transition to Z-DNA within the microsatellite, which eases transcription. In vitro studies show that the longer the tandem repeats sequence, the higher the transcription.
No studies on metalloproteinase polymorphism in NSTEACS have been carried out, so far.
This study has been planned to assess if patients admitted to the hospital for NSTEACS could be associated to a different in hospital clinical outcome according to the genetic polymorphism of these proteases.
Study design
- Observational model
- Defined population
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- non ST elevation acute coronary syndrome (NSTE ACS)
Key exclusion criteria (1 listed)
- STE acute myocardial infarction
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
Not reported in the source record.
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 8 Jun 2007.
- Background: PubMed 16574900Fiotti N, Altamura N, Fisicaro M, Carraro N, Uxa L, Grassi G, Torelli L, Gobbato R, Guarnieri G, Baxter BT, Giansante C. MMP-9 microsatellite polymorphism and susceptibility to carotid arteries atherosclerosis. Arterioscler Thromb Vasc Biol. 2006 Jun;26(6):1330-6. doi: 10.1161/01.ATV.0000219233.31702.c9. Epub 2006 Mar 30.
- Background: PubMed 7989608Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994 Dec;94(6):2493-503. doi: 10.1172/JCI117619.
- Background: PubMed 15823277Pollanen PJ, Lehtimaki T, Mikkelsson J, Ilveskoski E, Kunnas T, Perola M, Penttila A, Mattila KM, Nikkari ST, Syrjakoski K, Karhunen PJ. Matrix metalloproteinase3 and 9 gene promoter polymorphisms: joint action of two loci as a risk factor for coronary artery complicated plaques. Atherosclerosis. 2005 May;180(1):73-8. doi: 10.1016/j.atherosclerosis.2004.10.041. Epub 2004 Dec 18.
- Background: PubMed 10351963Terashima M, Akita H, Kanazawa K, Inoue N, Yamada S, Ito K, Matsuda Y, Takai E, Iwai C, Kurogane H, Yoshida Y, Yokoyama M. Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction. Circulation. 1999 Jun 1;99(21):2717-9. doi: 10.1161/01.cir.99.21.2717.
- Derived from this study: PubMed 21232745Fiotti N, Moretti ME, Bussani R, Altamura N, Zamolo F, Gerloni R, Ukovich L, Ober E, Silvestri F, Grassi G, Adovasio R, Giansante C. Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase functional polymorphisms. Atherosclerosis. 2011 Mar;215(1):153-9. doi: 10.1016/j.atherosclerosis.2010.12.010. Epub 2010 Dec 21.
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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.
Nicola FIOTTI, MD principal investigator
University of Trieste, ITALY
Carlo Giansante, MD study chair
University of Trieste, ITALY
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Unstable Angina, run by University of Trieste at 2 sites in Italy.
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 1 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 8 Jun 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00484406, which also lists 5 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 8 Jun 2007.