SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT03828422

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Arterial Function and Atherosclerosis in Patients With JAK2 V167F Positive Essential Thrombocythemia

The aim of the study is to examine (a) whether patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of arterial stiffness, pulse-wave velocity and coronary calcium score in a 4 year observation period, and (b) whether the burden of JAK2 V617F mutation correlates with the measured vascular parameters. All subjects will be examined twice. The first visit already took place between the years 2014 - 2015 and the second visit will take place between 2018-2019. All participants will have signed their informed consent before entering the study. Each visit will consist of completing a structured questionnaire (on personal and family medical history, risk factors for CVD and medication), physical examination, donating a blood sample for laboratory tests and undergoing carotid ultrasound and coronary calcium measurement oft the extent of coronary artery calcification. At the first and the second examination the JAK2 V617F allele burden, i.e. the percentage of mutated alleles, will be determined from genomic DNA in peripheral blood.

NCT03828422 Atherosclerosis
MeSH:Atherosclerosis Thrombocytosis Thrombocythemia, Essential
HPO:Atherosclerosis Thrombocytosis Type IV atherosclerotic lesion

1 Interventions

Name: imaging

Type: Diagnostic Test
Group Labels: 2

control group patients with essential thrombocythemia


Primary Outcomes

Description: Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid artery stiffness (expressed as two interrelated parameters, the beta-stiffness index and the pulse wave velocity) in a 4 year observation period?

Measure: Change of carotid artery stiffness (expressed by beta-stiffness index and pulse wave velocity) in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.

Time: the first visit in 2014-2015 and the second visit in 2018-2019

Description: Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid plaque score in a 4 year observation period? Scoring of atherosclerotic plaques will be done according to the Rotterdam Study. The presence of at least one plaque in each segment of the extracranial carotid arterial bed, (the common carotid artery and the bulb, the internal carotid artery and the external carotid artery) on either side is scored 1 point. Thus, the carotid plaque score ranges from 0 (absence of plaques, best) to 6 (plaques present in all segments on both sides, worst outcome).

Measure: Change of carotid artery plaque score in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.

Time: the first visit in 2014-2015 and the second visit in 2018-2019

Description: Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of coronary calcium score in a 4 year observation period?

Measure: Change of coronary calcium burden in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.

Time: the first visit in 2014-2015 and the second visit in 2018-2019

Description: Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show greater changes digital endothelial function, expressed as the Reactive Hyperemia Index (RHI), in a 4 year observation period? The RHI is the ratio of the pletysmographic amplitude of the digital arteries during maximal reactive hyperemia and the basal amplitude. RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).

Measure: Change of digital endothelial function, expressed as the Reactive Hyperemia Index, in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.

Time: the first visit in 2014-2015 and the second visit in 2018-2019

Description: Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.

Measure: Association of the JAK2 V617F mutation burden with the coronary calcium burden.

Time: at inclusion in the years 2014-2015, and at the second visit in 2018-2019

Time Perspective: Prospective

Case-Control


There are 2 SNPs

SNPs


1 V167F

Arterial Function and Atherosclerosis in Patients With JAK2 V167F Positive Essential Thrombocythemia. --- V167F ---


2 V617F

Arterial Function and Atherosclerosis in Essential Thrombocythemia The aim of the study is to examine (a) whether patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of arterial stiffness, pulse-wave velocity and coronary calcium score in a 4 year observation period, and (b) whether the burden of JAK2 V617F mutation correlates with the measured vascular parameters. --- V617F ---

Arterial Function and Atherosclerosis in Essential Thrombocythemia The aim of the study is to examine (a) whether patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of arterial stiffness, pulse-wave velocity and coronary calcium score in a 4 year observation period, and (b) whether the burden of JAK2 V617F mutation correlates with the measured vascular parameters. --- V617F --- --- V617F ---

At the first and the second examination the JAK2 V617F allele burden, i.e. the percentage of mutated alleles, will be determined from genomic DNA in peripheral blood. --- V617F ---

Change of carotid artery stiffness (expressed by beta-stiffness index and pulse wave velocity) in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid artery stiffness (expressed as two interrelated parameters, the beta-stiffness index and the pulse wave velocity) in a 4 year observation period?. --- V617F ---

Change of carotid artery stiffness (expressed by beta-stiffness index and pulse wave velocity) in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid artery stiffness (expressed as two interrelated parameters, the beta-stiffness index and the pulse wave velocity) in a 4 year observation period?. --- V617F --- --- V617F ---

Change of carotid artery plaque score in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid plaque score in a 4 year observation period? --- V617F ---

Change of carotid artery plaque score in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid plaque score in a 4 year observation period? --- V617F --- --- V617F ---

Thus, the carotid plaque score ranges from 0 (absence of plaques, best) to 6 (plaques present in all segments on both sides, worst outcome).. Change of coronary calcium burden in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of coronary calcium score in a 4 year observation period?. --- V617F ---

Thus, the carotid plaque score ranges from 0 (absence of plaques, best) to 6 (plaques present in all segments on both sides, worst outcome).. Change of coronary calcium burden in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of coronary calcium score in a 4 year observation period?. --- V617F --- --- V617F ---

Change of digital endothelial function, expressed as the Reactive Hyperemia Index, in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show greater changes digital endothelial function, expressed as the Reactive Hyperemia Index (RHI), in a 4 year observation period? --- V617F ---

Change of digital endothelial function, expressed as the Reactive Hyperemia Index, in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show greater changes digital endothelial function, expressed as the Reactive Hyperemia Index (RHI), in a 4 year observation period? --- V617F --- --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F --- --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F --- --- V617F --- --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F --- --- V617F --- --- V617F --- --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F --- --- V617F --- --- V617F --- --- V617F --- --- V617F ---

40 patients (14 male and 26 female) with JAK2 V617F positive ET without clinically apparent cardiovascular disease signed the informed consent and were enrolled in the study in 2014 - 2015 for the first examination and 36 (12 male and 24 female) of them are expected to participate also in 2018-19. --- V617F ---

3. JAK2 V617F/G1849T allele burden The ipsogen JAK2 MutaQuant Kit, Qiagen (ZDA) (Ref: No. 673523) will be used for the detection and quantification of JAK2 V617F/G1849T allele in genomic DNA extracted from peripheral blood of patients and also control subjects. --- V617F ---

3. JAK2 V617F/G1849T allele burden The ipsogen JAK2 MutaQuant Kit, Qiagen (ZDA) (Ref: No. 673523) will be used for the detection and quantification of JAK2 V617F/G1849T allele in genomic DNA extracted from peripheral blood of patients and also control subjects. --- V617F --- --- V617F ---

A SNP specific primer selectively amplifies the JAK2 V617F allele which is detected with a real-time qPCR instrument that quantifies the PCR products. --- V617F ---

The JAK2 V617F allele burden will be calculated and expressed as the percentage of JAK2 V617F mutated alleles throughout the whole JAK2 record. --- V617F ---

The JAK2 V617F allele burden will be calculated and expressed as the percentage of JAK2 V617F mutated alleles throughout the whole JAK2 record. --- V617F --- --- V617F ---

The association between the parameters of vascular function / morphology and the JAK2 V617F allele burden will be assessed by the Pearson correlation coefficient. --- V617F ---



HPO Nodes


HPO:
Protein Mutations 0
SNP 0