Coronary Artery DiseaseNCT03646019
Serum Oxidative Status as a Potential Predictor of Coronary Artery Disease.
An observational study of Coronary Artery Disease and Paraoxanase 1, run by Prof. Tony hayek MD.
Trial summary
Coronary artery disease (CAD) is a major cause of death and disability in developed countries.Human studies revealed a significant association between serum oxidative status using PON1, TBARS and thiol levels and the presence of CAD and its severity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Paraoxanase 1, Thiobarbituric Acid Reactive Substances
- How many people
- 200 participants
- Where
- No sites listed yet
- Study dates
- Sep 2018to Mar 2019
- 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
Study population: patients admitted to the chest pain unit (CPU) in the Department of Internal Medicine E' in the Rambam Medical Health center - Israel after they presented to the ED with acute chest pain, suspected to be of cardiac origin and seems to be suitable for further investigation by a cardiac CT scan. Participants will have no previous history of CAD. E.C.G at admission is with no signs of myocardial ischemia and cardiac biomarkers are normal.
Who may be able to join
- patients admitted to the chest pain unit (CPU) in the Department of Internal Medicine E' in the Rambam Medical Health center - Israel after they presented to the ED with acute chest pain, suspected to be of cardiac origin and seems to be suitable for further investigation by a cardiac CT scan. Participants will have no previous history of CAD. E.C.G at admission is with no signs of myocardial ischemia and cardiac biomarkers are normal.
Who cannot join
- known CAD.
- allergy to iodine contrast agents.
- asthma exacerbation.
- current use of steroids or other immunomodulating drugs.
- renal insufficiency (creatinine level ≥ 1.5 mg/dl).
- contraindication for radiations, as in pregnant women.
Show all 10Show fewer
- fever during the last 48 hours prior to admission.
- concomitant inflammatory diseases (infections, auto immune disorders, kidney and liver diseases, and recent major surgical procedure).
- Subjects with valvular, myocardial or pericardial diseases.
- Poor CT image quality due to motion artifacts or inappropriate contrast delivery, resulting in non-diagnostic image quality.
Trial locations and contacts
No sites are listed yet.
About this study
Coronary artery disease (CAD) is a major cause of death and disability in developed countries.Human studies revealed a significant association between serum oxidative status using PON1, TBARS and thiol levels and the presence of CAD and its severity. However, these studies were addressing the severity of CAD depending on coronary angiography of patients presenting with ST elevation myocardial infarction, Non ST elevation myocardial infarction, unstable angina pectoris, while part of them even had a history of CAD. Others where admitted for an elective coronary angiography for suspected stable CAD while only few patients were assessed for atypical chest pain. This study thus aims to assess the relationship between PON1 activity, TBARS and thiol levels and the existence of CAD and its severity in patients with no previous history of CAD presenting to the emergency department (ED) with acute chest pain but with no evidence of acute myocardial infarction or acute E.C.G ischemic changes. Assessment with a Cardiac CT scan instead of coronary angiography will allow the investigators to study the status of coronary atherosclerosis and calcium burden in all participants, including those presenting with atypical chest pain that most probably will not be referred by physicians to a coronary angiography. Further sub groups analysis will estimate this relationship particularly in low-intermediate risk groups depending on 3 different validated scoring systems - TIMI, GRACE and HEART score.
Read the detailed description
Oxidized low-density lipoprotein (LDL) has a pivotal role in the initiation as well as the progression of atherosclerosis. High-density lipoprotein (HDL) exerts a protective effect on the cardiovascular system, and serum HDL-cholesterol levels correlates inversely with atherosclerosis severity, since it protects against oxidative damage. It is believed that the anti oxidant activity of HDL is mainly determined by the HDL-associated enzyme paraoxanase 1 (PON1). The direct role of PON1 in reducing oxidative stress was demonstrated in studies using the PON1 knock out mice model and the human PON1 transgenic mice model. HDL particles isolated from PON1-deficient mice were unable to inhibit LDL oxidation in cultured arterial cells, in contrast to the HDL isolated from control mice. Moreover, HDL isolated from PON1 transgenic mice (that exhibited 3-fold increase in PON1 activity) was more effective in protecting LDL against oxidation compared to control / wild type mice. PON1 was shown to inhibit cholesterol influx by reducing the formation of oxidized LDL, increasing the breakdown of specific oxidized lipids in oxidized LDL, and decreasing macrophage uptake of oxidized LDL. PON1 also inhibits cholesterol biosynthesis and stimulates HDL-mediated cholesterol efflux from macrophages. Human studies revealed a significant association between decreased PON1 activity and increased risk of CAD. Mean PON1 activity levels were lower in patients with acute myocardial infarction (AMI) than stable CAD patients and highest level were observed in control patients. In patients with AMI, PON1 activity increased significantly within 6 weeks of the acute event, even though it was still markedly lower as compared to the stable CAD patients. Suggesting that sudden lowering of serum PON1 activity in a population which already has lower activity may be one of the risk factors for development of AMI. Ayub et al. has reported that serum PON1 activity was already decreased within 2 hours of the onset of symptoms of AMI and remained low subsequently, suggesting that the decreased PON1 activity may have preceded the acute event. A prospective study reported that low serum PON1 activity is a predictive risk factor for subsequent coronary events. Moreover, PON1 activity has presented a possible biochemical marker for CAD severity assessed by coronary angiography. Thiobarbituric acid reactive substances (TBARS) is an increased lipid peroxidation indicator that was found to be increased in CAD. A weak but significant correlation was also observed between levels of TBARS and angiographic progression of disease, especially moderate coronary artery stenosis. Elif Azarsiz et al. propose that the elevation in TBARS levels might be a more marked indicator for the degree of atherosclerosis than the insufficiency in antioxidant enzymes such as PON1. Thiol / -SH levels were found to be lower in the CAD group compared with the non CAD group and control group. Decreased serum thiol levels were associated with the presence and severity of CAD.
In this study first set of blood samples will be obtained at presentation to the ED and later on at the department of internal medicine E'in the Rambam's Medical Health Center, including CBC count, creatinine, electrolytes and two high sensitive troponin measurements. A second set of blood samples will be obtained at the morning of the cardiac CT scan after 10-12-h over-night fast, including serum level of HbA1C, CRP, kidney and liver function, total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. All parameters will be measured on fresh blood samples at the Rambam's Medical Health Center biochemical and endocrine laboratories. Serum oxidative status will be determined by collecting additional blood tube (5 ml of blood) at the morning of the cardiac CT scan. After centrifuging the clotted sample, serum will be separated and stored at minus 40 celsius for further analysis of PON-1 / aryl esterase activity, measurement of protein thiol groups / glutathione and measurement of serum level of thiobarbituric acid reactive substances (TBARS, measured as malondialdehyde [MDA] equivalents), at Lipid Research Laboratory of the Rappaport Faculty of Medicine at the Technion, Haifa - Israel.
Patients not already on beta-blocking drugs will receive oral metoprolol (50-200 mg) for heart rates over 65 beats/min. An additional intravenous metoprolol (5-10 mg) will be administered to achieve a target heart rate <65 beats/min 5-15 minutes before the test. However, no patient will be excluded because of a heart rate above this target.
The cardiac CT scan images will be interpreted by a panel of experienced radiologists blinded to the study, at Rambam Medical Health Center. The degree of coronary obstruction will be measured in terms of the percent of stenosis. Participant with stenosis less than or equal to 49% is considered to have a non significant CAD. Participant with stenosis more than 49% is considered to have a significant CAD. Calcium burden will be measured by the Agatston score. Subjects with significant stenosis in the cardiac CT scan will undergo coronary angiography for a further assessment of the degree of stenosis. Result of the coronary angiography will be assessed in relation to the measurement of serum oxidative status as well.
In this study hypertension will be defined as a DBP ≥ 90 mmHg, SBP ≥ 140 mmHg measured using a calibrated electronic blood pressure machine in both arms while sitting after at least 30 min of rest, and the average of 3 recording will be used or self reported use of anti hypertensive drug. Diabetes mellitus (DM) will be diagnosed if the HbA1C is ≥ 6.5 % or if the patient is treated with insulin or oral hypoglycemic agents. Body mass index (BMI) will be computed as weight /height squared (k/m2).
- Conditions
- Coronary Artery Disease, Paraoxanase 1, Thiobarbituric Acid Reactive Substances, Thiol Groups
- Keywords
- Coronary artery disease, paraoxanase 1, Thiobarbituric Acid Reactive Substances, Thiol groups
- Medical subject headings
- Coronary Artery Disease
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 |
|---|---|---|
| Normal coronary arteries | Not described | |
| Non significant coronary artery disease | Not described | |
| Significant coronary artery disease | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
The presence and severity of coronary artery disease assessed by a cardiac CT scan / coronary angiography.
The presence of coronary artery disease is defined as the presence of any atherosclerotic plaque leading to any percentage of coronary artery stenosis. The severity of coronary artery disease is defined either as significant or non significant. A Non significant coronary artery disease is defined as any coronary artery stenosis less than or equal to 49%. A Significant coronary artery disease is defined as any coronary artery stenosis more than 49%.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study startSep 2018 (estimated)
- Primary completionMar 2019 (estimated)
- Study completionMar 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (34)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prof. Tony hayek MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Prof. Tony hayek MD, Rambam Health Care Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03646019
- Sponsor's protocol ID
- 0373-18-RMB
- Status last verified
- Aug 2018
- First submitted
- 10 Aug 2018
- Last updated
- 24 Aug 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Sanchis-Gomar F, Perez-Quilis C, Leischik R, Lucia A. Epidemiology of coronary heart disease and acute coronary syndrome. Ann Transl Med. 2016 Jul;4(13):256. doi: 10.21037/atm.2016.06.33.
PubMed 27500157Zhou C, Cao J, Shang L, Tong C, Hu H, Wang H, Fan D, Yu H. Reduced paraoxonase 1 activity as a marker for severe coronary artery disease. Dis Markers. 2013;35(2):97-103. doi: 10.1155/2013/816189. Epub 2013 Jul 28.
PubMed 24167353Rye KA, Barter PJ. Cardioprotective functions of HDLs. J Lipid Res. 2014 Feb;55(2):168-79. doi: 10.1194/jlr.R039297. Epub 2013 Jun 27.
PubMed 23812558Gur M, Cayli M, Ucar H, Elbasan Z, Sahin DY, Gozukara MY, Selek S, Koyunsever NY, Seker T, Turkoglu C, Kaypakli O, Aksoy N. Paraoxonase (PON1) activity in patients with subclinical thoracic aortic atherosclerosis. Int J Cardiovasc Imaging. 2014 Jun;30(5):889-95. doi: 10.1007/s10554-014-0407-y. Epub 2014 Apr 4.
PubMed 24700021Singh K, Singh R, Chandra S, Tyagi S. Paraoxonase-1 is a better indicator than HDL of Atherosclerosis - A pilot study in North Indian population. Diabetes Metab Syndr. 2018 May;12(3):275-278. doi: 10.1016/j.dsx.2017.12.006. Epub 2017 Dec 14.
PubMed 29254890Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature. 1998 Jul 16;394(6690):284-7. doi: 10.1038/28406.
PubMed 9685159Shih DM, Xia YR, Wang XP, Miller E, Castellani LW, Subbanagounder G, Cheroutre H, Faull KF, Berliner JA, Witztum JL, Lusis AJ. Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem. 2000 Jun 9;275(23):17527-35. doi: 10.1074/jbc.M910376199.
PubMed 10748217Oda MN, Bielicki JK, Ho TT, Berger T, Rubin EM, Forte TM. Paraoxonase 1 overexpression in mice and its effect on high-density lipoproteins. Biochem Biophys Res Commun. 2002 Jan 25;290(3):921-7. doi: 10.1006/bbrc.2001.6295.
PubMed 11798161Tward A, Xia YR, Wang XP, Shi YS, Park C, Castellani LW, Lusis AJ, Shih DM. Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation. 2002 Jul 23;106(4):484-90. doi: 10.1161/01.cir.0000023623.87083.4f.
PubMed 12135950Aviram M, Rosenblat M. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med. 2004 Nov 1;37(9):1304-16. doi: 10.1016/j.freeradbiomed.2004.06.030.
PubMed 15454271Zhao Y, Ma Y, Fang Y, Liu L, Wu S, Fu D, Wang X. Association between PON1 activity and coronary heart disease risk: a meta-analysis based on 43 studies. Mol Genet Metab. 2012 Jan;105(1):141-8. doi: 10.1016/j.ymgme.2011.09.018. Epub 2011 Sep 22.
PubMed 22030099Gocmen AY, Gumuslu S, Semiz E. Association between paraoxonase-1 activity and lipid peroxidation indicator levels in people living in the Antalya region with angiographically documented coronary artery disease. Clin Cardiol. 2004 Jul;27(7):426-30. doi: 10.1002/clc.4960270714.
PubMed 15298047Ding J, Chen Q, Zhuang X, Feng Z, Xu L, Chen F. Low paraoxonase 1 arylesterase activity and high von Willebrand factor levels are associated with severe coronary atherosclerosis in patients with non-diabetic stable coronary artery disease. Med Sci Monit. 2014 Nov 25;20:2421-9. doi: 10.12659/MSM.890911.
PubMed 25420483Graner M, James RW, Kahri J, Nieminen MS, Syvanne M, Taskinen MR. Association of paraoxonase-1 activity and concentration with angiographic severity and extent of coronary artery disease. J Am Coll Cardiol. 2006 Jun 20;47(12):2429-35. doi: 10.1016/j.jacc.2006.01.074. Epub 2006 May 26.
PubMed 16781370Jayakumari N, Thejaseebai G. High prevalence of low serum paraoxonase-1 in subjects with coronary artery disease. J Clin Biochem Nutr. 2009 Nov;45(3):278-84. doi: 10.3164/jcbn.08-255. Epub 2009 Oct 28.
PubMed 19902017
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serum Oxidative Status as a Potential Predictor of Coronary Artery Disease.
- ClinicalTrials.gov ID
- NCT03646019
- Acronym / sponsor ID
- 0373-18-RMB
- Conditions
- Coronary Artery Disease, Paraoxanase 1, Thiobarbituric Acid Reactive Substances, Thiol Groups
- Keywords
- Coronary artery disease, paraoxanase 1, Thiobarbituric Acid Reactive Substances, Thiol groups
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Prof. Tony hayek MDUniversity, hospital or other
- Study start
- Sep 2018 (estimated)
- Primary completion
- Mar 2019 (estimated)
- Study completion
- Mar 2019 (estimated)
- First posted
- 24 Aug 2018 (actual)
- 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.
Coronary artery disease (CAD) is a major cause of death and disability in developed countries.Human studies revealed a significant association between serum oxidative status using PON1, TBARS and thiol levels and the presence of CAD and its severity. However, these studies were addressing the severity of CAD depending on coronary angiography of patients presenting with ST elevation myocardial infarction, Non ST elevation myocardial infarction, unstable angina pectoris, while part of them even had a history of CAD. Others where admitted for an elective coronary angiography for suspected stable CAD while only few patients were assessed for atypical chest pain. This study thus aims to assess the relationship between PON1 activity, TBARS and thiol levels and the existence of CAD and its severity in patients with no previous history of CAD presenting to the emergency department (ED) with acute chest pain but with no evidence of acute myocardial infarction or acute E.C.G ischemic changes. Assessment with a Cardiac CT scan instead of coronary angiography will allow the investigators to study the status of coronary atherosclerosis and calcium burden in all participants, including those presenting with atypical chest pain that most probably will not be referred by physicians to a coronary angiography. Further sub groups analysis will estimate this relationship particularly in low-intermediate risk groups depending on 3 different validated scoring systems - TIMI, GRACE and HEART score.
Detailed description
Oxidized low-density lipoprotein (LDL) has a pivotal role in the initiation as well as the progression of atherosclerosis. High-density lipoprotein (HDL) exerts a protective effect on the cardiovascular system, and serum HDL-cholesterol levels correlates inversely with atherosclerosis severity, since it protects against oxidative damage. It is believed that the anti oxidant activity of HDL is mainly determined by the HDL-associated enzyme paraoxanase 1 (PON1). The direct role of PON1 in reducing oxidative stress was demonstrated in studies using the PON1 knock out mice model and the human PON1 transgenic mice model. HDL particles isolated from PON1-deficient mice were unable to inhibit LDL oxidation in cultured arterial cells, in contrast to the HDL isolated from control mice. Moreover, HDL isolated from PON1 transgenic mice (that exhibited 3-fold increase in PON1 activity) was more effective in protecting LDL against oxidation compared to control / wild type mice. PON1 was shown to inhibit cholesterol influx by reducing the formation of oxidized LDL, increasing the breakdown of specific oxidized lipids in oxidized LDL, and decreasing macrophage uptake of oxidized LDL. PON1 also inhibits cholesterol biosynthesis and stimulates HDL-mediated cholesterol efflux from macrophages. Human studies revealed a significant association between decreased PON1 activity and increased risk of CAD. Mean PON1 activity levels were lower in patients with acute myocardial infarction (AMI) than stable CAD patients and highest level were observed in control patients. In patients with AMI, PON1 activity increased significantly within 6 weeks of the acute event, even though it was still markedly lower as compared to the stable CAD patients. Suggesting that sudden lowering of serum PON1 activity in a population which already has lower activity may be one of the risk factors for development of AMI. Ayub et al. has reported that serum PON1 activity was already decreased within 2 hours of the onset of symptoms of AMI and remained low subsequently, suggesting that the decreased PON1 activity may have preceded the acute event. A prospective study reported that low serum PON1 activity is a predictive risk factor for subsequent coronary events. Moreover, PON1 activity has presented a possible biochemical marker for CAD severity assessed by coronary angiography. Thiobarbituric acid reactive substances (TBARS) is an increased lipid peroxidation indicator that was found to be increased in CAD. A weak but significant correlation was also observed between levels of TBARS and angiographic progression of disease, especially moderate coronary artery stenosis. Elif Azarsiz et al. propose that the elevation in TBARS levels might be a more marked indicator for the degree of atherosclerosis than the insufficiency in antioxidant enzymes such as PON1. Thiol / -SH levels were found to be lower in the CAD group compared with the non CAD group and control group. Decreased serum thiol levels were associated with the presence and severity of CAD.
In this study first set of blood samples will be obtained at presentation to the ED and later on at the department of internal medicine E'in the Rambam's Medical Health Center, including CBC count, creatinine, electrolytes and two high sensitive troponin measurements. A second set of blood samples will be obtained at the morning of the cardiac CT scan after 10-12-h over-night fast, including serum level of HbA1C, CRP, kidney and liver function, total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. All parameters will be measured on fresh blood samples at the Rambam's Medical Health Center biochemical and endocrine laboratories. Serum oxidative status will be determined by collecting additional blood tube (5 ml of blood) at the morning of the cardiac CT scan. After centrifuging the clotted sample, serum will be separated and stored at minus 40 celsius for further analysis of PON-1 / aryl esterase activity, measurement of protein thiol groups / glutathione and measurement of serum level of thiobarbituric acid reactive substances (TBARS, measured as malondialdehyde [MDA] equivalents), at Lipid Research Laboratory of the Rappaport Faculty of Medicine at the Technion, Haifa - Israel.
Patients not already on beta-blocking drugs will receive oral metoprolol (50-200 mg) for heart rates over 65 beats/min. An additional intravenous metoprolol (5-10 mg) will be administered to achieve a target heart rate <65 beats/min 5-15 minutes before the test. However, no patient will be excluded because of a heart rate above this target.
The cardiac CT scan images will be interpreted by a panel of experienced radiologists blinded to the study, at Rambam Medical Health Center. The degree of coronary obstruction will be measured in terms of the percent of stenosis. Participant with stenosis less than or equal to 49% is considered to have a non significant CAD. Participant with stenosis more than 49% is considered to have a significant CAD. Calcium burden will be measured by the Agatston score. Subjects with significant stenosis in the cardiac CT scan will undergo coronary angiography for a further assessment of the degree of stenosis. Result of the coronary angiography will be assessed in relation to the measurement of serum oxidative status as well.
In this study hypertension will be defined as a DBP ≥ 90 mmHg, SBP ≥ 140 mmHg measured using a calibrated electronic blood pressure machine in both arms while sitting after at least 30 min of rest, and the average of 3 recording will be used or self reported use of anti hypertensive drug. Diabetes mellitus (DM) will be diagnosed if the HbA1C is ≥ 6.5 % or if the patient is treated with insulin or oral hypoglycemic agents. Body mass index (BMI) will be computed as weight /height squared (k/m2).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Normal coronary arteries | – | – |
| Non significant coronary artery disease | – | – |
| Significant coronary artery disease | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients admitted to the chest pain unit (CPU) in the Department of Internal Medicine E' in the Rambam Medical Health center - Israel after they presented to the ED with acute chest pain, suspected to be of cardiac origin and seems to be suitable for further investigation by a cardiac CT scan. Participants will have no previous history of CAD. E.C.G at admission is with no signs of myocardial ischemia and cardiac biomarkers are normal.
Key inclusion criteria (1 listed)
- patients admitted to the chest pain unit (CPU) in the Department of Internal Medicine E' in the Rambam Medical Health center - Israel after they presented to the ED with acute chest pain, suspected to be of cardiac origin and seems to be suitable for further investigation by a cardiac CT scan. Participants will have no previous history of CAD. E.C.G at admission is with no signs of myocardial ischemia and cardiac biomarkers are normal.
Key exclusion criteria (10 listed)
- known CAD.
- allergy to iodine contrast agents.
- asthma exacerbation.
- current use of steroids or other immunomodulating drugs.
- renal insufficiency (creatinine level ≥ 1.5 mg/dl).
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
The presence and severity of coronary artery disease assessed by a cardiac CT scan / coronary angiography.
Time frame: 7 days
The presence of coronary artery disease is defined as the presence of any atherosclerotic plaque leading to any percentage of coronary artery stenosis. The severity of coronary artery disease is defined either as significant or non significant. A Non significant coronary artery disease is defined as any coronary artery stenosis less than or equal to 49%. A Significant coronary artery disease is defined as any coronary artery stenosis more than 49%.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2018.
- Background: PubMed 27500157Sanchis-Gomar F, Perez-Quilis C, Leischik R, Lucia A. Epidemiology of coronary heart disease and acute coronary syndrome. Ann Transl Med. 2016 Jul;4(13):256. doi: 10.21037/atm.2016.06.33.
- Background: PubMed 24167353Zhou C, Cao J, Shang L, Tong C, Hu H, Wang H, Fan D, Yu H. Reduced paraoxonase 1 activity as a marker for severe coronary artery disease. Dis Markers. 2013;35(2):97-103. doi: 10.1155/2013/816189. Epub 2013 Jul 28.
- Background: PubMed 23812558Rye KA, Barter PJ. Cardioprotective functions of HDLs. J Lipid Res. 2014 Feb;55(2):168-79. doi: 10.1194/jlr.R039297. Epub 2013 Jun 27.
- Background: PubMed 24700021Gur M, Cayli M, Ucar H, Elbasan Z, Sahin DY, Gozukara MY, Selek S, Koyunsever NY, Seker T, Turkoglu C, Kaypakli O, Aksoy N. Paraoxonase (PON1) activity in patients with subclinical thoracic aortic atherosclerosis. Int J Cardiovasc Imaging. 2014 Jun;30(5):889-95. doi: 10.1007/s10554-014-0407-y. Epub 2014 Apr 4.
- Background: PubMed 29254890Singh K, Singh R, Chandra S, Tyagi S. Paraoxonase-1 is a better indicator than HDL of Atherosclerosis - A pilot study in North Indian population. Diabetes Metab Syndr. 2018 May;12(3):275-278. doi: 10.1016/j.dsx.2017.12.006. Epub 2017 Dec 14.
- Background: PubMed 9685159Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature. 1998 Jul 16;394(6690):284-7. doi: 10.1038/28406.
- Background: PubMed 10748217Shih DM, Xia YR, Wang XP, Miller E, Castellani LW, Subbanagounder G, Cheroutre H, Faull KF, Berliner JA, Witztum JL, Lusis AJ. Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem. 2000 Jun 9;275(23):17527-35. doi: 10.1074/jbc.M910376199.
- Background: PubMed 11798161Oda MN, Bielicki JK, Ho TT, Berger T, Rubin EM, Forte TM. Paraoxonase 1 overexpression in mice and its effect on high-density lipoproteins. Biochem Biophys Res Commun. 2002 Jan 25;290(3):921-7. doi: 10.1006/bbrc.2001.6295.
- Background: PubMed 12135950Tward A, Xia YR, Wang XP, Shi YS, Park C, Castellani LW, Lusis AJ, Shih DM. Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation. 2002 Jul 23;106(4):484-90. doi: 10.1161/01.cir.0000023623.87083.4f.
- Background: PubMed 15454271Aviram M, Rosenblat M. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med. 2004 Nov 1;37(9):1304-16. doi: 10.1016/j.freeradbiomed.2004.06.030.
- Background: PubMed 22030099Zhao Y, Ma Y, Fang Y, Liu L, Wu S, Fu D, Wang X. Association between PON1 activity and coronary heart disease risk: a meta-analysis based on 43 studies. Mol Genet Metab. 2012 Jan;105(1):141-8. doi: 10.1016/j.ymgme.2011.09.018. Epub 2011 Sep 22.
- Background: PubMed 15298047Gocmen AY, Gumuslu S, Semiz E. Association between paraoxonase-1 activity and lipid peroxidation indicator levels in people living in the Antalya region with angiographically documented coronary artery disease. Clin Cardiol. 2004 Jul;27(7):426-30. doi: 10.1002/clc.4960270714.
- GRACE score calculatorLink provided by the sponsor.
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronary Artery Disease and Paraoxanase 1, run by Prof. Tony hayek MD.
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 10 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 24 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
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 Tony Hayek, professor (+ 972523782009, t_hayek@rambam.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The presence and severity of coronary artery disease assessed by a cardiac CT scan / coronary angiography. (time frame: 7 days). 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 NCT03646019, which also lists 34 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 24 Aug 2018.