<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02972008</url>
  </required_header>
  <id_info>
    <org_study_id>2015_92</org_study_id>
    <secondary_id>2016-A01035-46</secondary_id>
    <secondary_id>PHRCI_2015</secondary_id>
    <nct_id>NCT02972008</nct_id>
  </id_info>
  <brief_title>Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly</brief_title>
  <acronym>METHYSTROKE</acronym>
  <official_title>Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Lille</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Over the past ten years, the number of endovascular procedures has increased by 5% per year&#xD;
      in Europe with the development of interventional cardiology, such as percutaneous coronary&#xD;
      angioplasty, aortic valve replacements (TAVR), and vascular endoprosthesis.&#xD;
&#xD;
      The neurological lesions detected on cerebral MRI caused by these endovascular procedures are&#xD;
      frequent with an incidence of about 30-70%. These events, although subclinical, have an&#xD;
      impact on morbidity and mortality and especially on long-term cognitive decline.&#xD;
&#xD;
      TAVR is the reference treatment for symptomatic elderly patients with stenosis of the aortic&#xD;
      valve, considered by a multidisciplinary &quot;Heart Team&quot; as at high surgical risk due to&#xD;
      comorbidities, age and high perioperative risk scores ( Euroscore 2 and STS scores). Despite&#xD;
      the net clinical benefit, an increase of silent neurological events was detected on&#xD;
      post-procedural cerebral MRI with an incidence of approximately 70%.&#xD;
&#xD;
      The epigenetic involvement in the occurrence of ischemic cerebral lesions is still largely&#xD;
      unknown. Epigenetic mechanisms, such as DNA methylation, can be associated with aging&#xD;
      processes and modulate the risk of developing cerebrovascular pathologies. They are likely to&#xD;
      provide new biomarkers that predict the risk of brain damage.&#xD;
&#xD;
      Hypomethylation of leukocyte DNA is directly related to atherosclerosis in humans. This&#xD;
      hypomethylation of DNA would represent an easily measurable marker reflecting the presence&#xD;
      and progression of atherosclerosis. Because atherosclerotic lesions often precede the&#xD;
      clinical manifestation of ischemic cardiovascular disease, such as ischemic heart disease and&#xD;
      stroke, DNA hypomethylation could be used to identify individuals at risk for cerebrovascular&#xD;
      events.&#xD;
&#xD;
      The investigator hypothesize that hypomethylation of leukocyte DNA can predict the risk of&#xD;
      developing new ischemic brain lesions especially after a TAVI procedure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a french multicenter prospective cohort study. Patients with severe symptomatic&#xD;
      aortic stenosis referred for a TAVI procedure to the cardiology departments of the university&#xD;
      hospitals of Lille, Caen, Amiens and the Pitié-Salpêtrière hospital (APHP) are analyzed for&#xD;
      inclusion in this prospective study. The cases are selected after a discussion between the&#xD;
      members of the local TAVI &quot;Heart Team&quot; (cardiologists, cardiac surgeons, anesthetists), as&#xD;
      recommended by the guidelines of the European Society of Cardiology. Written consent is&#xD;
      obtained in accordance with international recommendations for clinical research (Helsinki&#xD;
      Declaration). Participation in the study is proposed to patients during preoperative&#xD;
      consultation.&#xD;
&#xD;
      The collection of clinical data, including postoperative cerebral MRI, is collected&#xD;
      prospectively during hospitalization and during the clinical visit to each institution at one&#xD;
      year. An evaluation of cognitive function is performed by a mini-mental state (MMS) the day&#xD;
      before the TAVI intervention and then at 1 year. The study ends after the last evaluation. A&#xD;
      cerebral MRI is performed within 1-3 days after the TAVI procedure to detect new cerebral&#xD;
      ischemic lesions (emboli).&#xD;
&#xD;
      Blood samples will be taken during the patient's stay: the day before TAVI, during the&#xD;
      procedure and after the TAVI procedure at day 1 and day 4.&#xD;
&#xD;
      The follow-up visit to 1 year will be conducted by cardiologists or cardiac surgeons with an&#xD;
      evaluation of the cognitive function by the mini-mental state (MMS).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 9, 2017</start_date>
  <completion_date type="Anticipated">February 2024</completion_date>
  <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Pre-operative leukocyte DNA methylation rate</measure>
    <time_frame>Within one week after the procedure</time_frame>
    <description>This rate will be measured by the LUMA method in patients treated with TAVI according to the presence of at least one new cerebral ischemic lesion and/or microbleeds cerebral lesion appearing on post-procedural MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Variation of the leukocyte DNA methylation rate during the TAVI procedure</measure>
    <time_frame>At time between the pre (day-1) and postprocedural (day 1) samples</time_frame>
    <description>This rate will be measured by the LINE-1 method in all patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre-operative leukocyte DNA methylation rate (stroke/TIA)</measure>
    <time_frame>One day before the procedure and within one week after the procedure</time_frame>
    <description>This rate will be measured by the LUMA method in patients treated with TAVI according to the presence of a neurological deficit (stroke, transient ischemic attack)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>At 1 year after procedure</time_frame>
    <description>The mortality in patients treated with TAVI according to the presence of at least one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion detected on postoperative cerebral MRI and / or postprocedural ischemic stroke / TIA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MMSE score variation</measure>
    <time_frame>At day-1 before TAVI procedure, at 6 months and at 1 year after procedure</time_frame>
    <description>The MMSE score variation is compared according to the presence or not of at least one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of EQ-5D questionnaire</measure>
    <time_frame>At day-1 before TAVI procedure, at 6 months and at 1 year after procedure</time_frame>
    <description>The evolution of quality of life is compared to the occurrence of new cerebral events one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of modified Rankin Scale (mRS)</measure>
    <time_frame>At day-1 before TAVI procedure, at 6 months and at 1 year after procedure</time_frame>
    <description>The MRS (measure degree of disability- troke) is compared to the occurrence of new cerebral events one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of National Institutes of Health Stroke Scale (NIHSS)</measure>
    <time_frame>At day-1 before TAVI procedure, at 6 months and at 1 year after procedure</time_frame>
    <description>TheNIHSS (quantify the impairment caused by a stroke) is compared to the occurrence of new cerebral events one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical and Biological predictors of new cerebral events</measure>
    <time_frame>At day-1 before TAVI procedure, at 6 months and at 1 year after procedure</time_frame>
    <description>The clinical (measured before the procedure) and biological characteristics of the patients (measured before the procedure and after the procedure) and of the peri-procedural parameters associated with the occurrence of new events detected on post-procedural MRI (new ischemic and/or new microbleeds cerebral lesion appearing on post-procedural MRI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemostasis predictors of new cerebral events</measure>
    <time_frame>At day-1 before TAVI procedure, at 6 months and at 1 year after procedure</time_frame>
    <description>Hemostasis parameters (measured before the procedure and after the procedure) including Willebrand factor parameters associated with the occurrence of new events detected on postoperative MRI (new ischemic and/or new microbleeds cerebral lesion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of complications in peri-procedural according to VARC-2 criteria</measure>
    <time_frame>Within one week after the procedure</time_frame>
    <description>Evaluation of multi criteria according to the Valve academic Research Consortium (VARC-2)</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">542</enrollment>
  <condition>Cognitive Decline</condition>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>Cerebral Lesion</arm_group_label>
    <description>Patient over 70 years with severe aortic stenosis requiring percutaneous aortic valvular replacement (TAVI) having at least one new cerebral ischemic lesion on postoperative cerebral MRI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Cerebral Lesion</arm_group_label>
    <description>Patient over 70 years with severe aortic stenosis requiring percutaneous aortic valvular replacement (TAVI) with no cerebral ischemic lesion on postoperative cerebral MRI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>patients with constitutional von Willebrand factor (vWF) deficiency</arm_group_label>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      We compare the pre-operative leukocyte DNA methylation rate measured by the Luminometric&#xD;
      Methylation Assay (LUMA) method in patients treated with TAVI and patients with&#xD;
      constitutional von Willebrand factor (vWF) deficiency according to the presence or absence of&#xD;
      at least one new cerebral ischemic lesion detected on postoperative cerebral MRI.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients over 70 years with severe aortic stenosis requiring percutaneous aortic valve&#xD;
        replacement (TAVI)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients over 70 years with severe aortic stenosis requiring percutaneous aortic valve&#xD;
             replacement (TAVI)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient contraindicated for the TAVI procedure&#xD;
&#xD;
          -  Patient with a pace-maker&#xD;
&#xD;
          -  Patient with contra-indication for cerebral MRI&#xD;
&#xD;
          -  Ongoing cancer&#xD;
&#xD;
          -  Patient already involved in therapeutic research&#xD;
&#xD;
          -  Major persons under protection of justice.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicolas Debry, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nicolas Debry, MD</last_name>
    <phone>+33 3 20 44 59 62</phone>
    <phone_ext>+33</phone_ext>
    <email>nicolas.debry@chru-lille.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital cardiologie, CHRU</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Nicolas Debry, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Ghanem A, Kocurek J, Sinning JM, Wagner M, Becker BV, Vogel M, Schroder T, Wolfsgruber S, Vasa-Nicotera M, Hammerstingl C, Schwab JO, Thomas D, Werner N, Grube E, Nickenig G, Muller A. Cognitive trajectory after transcatheter aortic valve implantation. Circ Cardiovasc Interv. 2013 Dec;6(6):615-24. doi: 10.1161/CIRCINTERVENTIONS.112.000429. Epub 2013 Oct 15.</citation>
    <PMID>24129642</PMID>
  </reference>
  <reference>
    <citation>Kahlert P, Knipp SC, Schlamann M, Thielmann M, Al-Rashid F, Weber M, Johansson U, Wendt D, Jakob HG, Forsting M, Sack S, Erbel R, Eggebrecht H. Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study. Circulation. 2010 Feb 23;121(7):870-8. doi: 10.1161/CIRCULATIONAHA.109.855866.</citation>
    <PMID>20177005</PMID>
  </reference>
  <reference>
    <citation>Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekstrom TJ, Harris TB, Launer LJ, Eiriksdottir G, Leppert MF, Sapienza C, Gudnason V, Feinberg AP. Intra-individual change over time in DNA methylation with familial clustering. JAMA. 2008 Jun 25;299(24):2877-83. doi: 10.1001/jama.299.24.2877.</citation>
    <PMID>18577732</PMID>
  </reference>
  <reference>
    <citation>Baccarelli A, Wright R, Bollati V, Litonjua A, Zanobetti A, Tarantini L, Sparrow D, Vokonas P, Schwartz J. Ischemic heart disease and stroke in relation to blood DNA methylation. Epidemiology. 2010 Nov;21(6):819-28. doi: 10.1097/EDE.0b013e3181f20457.</citation>
    <PMID>20805753</PMID>
  </reference>
  <reference>
    <citation>Van Belle E, Juthier F, Susen S, Vincentelli A, Iung B, Dallongeville J, Eltchaninoff H, Laskar M, Leprince P, Lievre M, Banfi C, Auffray JL, Delhaye C, Donzeau-Gouge P, Chevreul K, Fajadet J, Leguerrier A, Prat A, Gilard M, Teiger E; FRANCE 2 Investigators. Postprocedural aortic regurgitation in balloon-expandable and self-expandable transcatheter aortic valve replacement procedures: analysis of predictors and impact on long-term mortality: insights from the FRANCE2 Registry. Circulation. 2014 Apr 1;129(13):1415-27. doi: 10.1161/CIRCULATIONAHA.113.002677. Epub 2014 Feb 24.</citation>
    <PMID>24566199</PMID>
  </reference>
  <reference>
    <citation>Gilard M, Eltchaninoff H, Iung B, Donzeau-Gouge P, Chevreul K, Fajadet J, Leprince P, Leguerrier A, Lievre M, Prat A, Teiger E, Lefevre T, Himbert D, Tchetche D, Carrie D, Albat B, Cribier A, Rioufol G, Sudre A, Blanchard D, Collet F, Dos Santos P, Meneveau N, Tirouvanziam A, Caussin C, Guyon P, Boschat J, Le Breton H, Collart F, Houel R, Delpine S, Souteyrand G, Favereau X, Ohlmann P, Doisy V, Grollier G, Gommeaux A, Claudel JP, Bourlon F, Bertrand B, Van Belle E, Laskar M; FRANCE 2 Investigators. Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med. 2012 May 3;366(18):1705-15. doi: 10.1056/NEJMoa1114705.</citation>
    <PMID>22551129</PMID>
  </reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>January 31, 2022</last_update_submitted>
  <last_update_submitted_qc>January 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aortic stenosis</keyword>
  <keyword>Transaortic valve replacement</keyword>
  <keyword>stroke</keyword>
  <keyword>Epigenetic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02972008
org study id: 2015_92
secondary id: 2016-A01035-46
secondary id: PHRCI_2015
nct id: NCT02972008
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Over the past ten years, the number of endovascular procedures has increased by 5% per year
      in Europe with the development of interventional cardiology, such as percutaneous coronary
      angioplasty, aortic valve replacements (TAVR), and vascular endoprosthesis.

      The neurological lesions detected on cerebral MRI caused by these endovascular procedures are
      frequent with an incidence of about 30-70%. These events, although subclinical, have an
      impact on morbidity and mortality and especially on long-term cognitive decline.

      TAVR is the reference treatment for symptomatic elderly patients with stenosis of the aortic
      valve, considered by a multidisciplinary "Heart Team" as at high surgical risk due to
      comorbidities, age and high perioperative risk scores ( Euroscore 2 and STS scores). Despite
      the net clinical benefit, an increase of silent neurological events was detected on
      post-procedural cerebral MRI with an incidence of approximately 70%.

      The epigenetic involvement in the occurrence of ischemic cerebral lesions is still largely
      unknown. Epigenetic mechanisms, such as DNA methylation, can be associated with aging
      processes and modulate the risk of developing cerebrovascular pathologies. They are likely to
      provide new biomarkers that predict the risk of brain damage.

      Hypomethylation of leukocyte DNA is directly related to atherosclerosis in humans. This
      hypomethylation of DNA would represent an easily measurable marker reflecting the presence
      and progression of atherosclerosis. Because atherosclerotic lesions often precede the
      clinical manifestation of ischemic cardiovascular disease, such as ischemic heart disease and
      stroke, DNA hypomethylation could be used to identify individuals at risk for cerebrovascular
      events.

      The investigator hypothesize that hypomethylation of leukocyte DNA can predict the risk of
      developing new ischemic brain lesions especially after a TAVI procedure.
This is a french multicenter prospective cohort study. Patients with severe symptomatic
      aortic stenosis referred for a TAVI procedure to the cardiology departments of the university
      hospitals of Lille, Caen, Amiens and the Pitié-Salpêtrière hospital (APHP) are analyzed for
      inclusion in this prospective study. The cases are selected after a discussion between the
      members of the local TAVI "Heart Team" (cardiologists, cardiac surgeons, anesthetists), as
      recommended by the guidelines of the European Society of Cardiology. Written consent is
      obtained in accordance with international recommendations for clinical research (Helsinki
      Declaration). Participation in the study is proposed to patients during preoperative
      consultation.

      The collection of clinical data, including postoperative cerebral MRI, is collected
      prospectively during hospitalization and during the clinical visit to each institution at one
      year. An evaluation of cognitive function is performed by a mini-mental state (MMS) the day
      before the TAVI intervention and then at 1 year. The study ends after the last evaluation. A
      cerebral MRI is performed within 1-3 days after the TAVI procedure to detect new cerebral
      ischemic lesions (emboli).

      Blood samples will be taken during the patient's stay: the day before TAVI, during the
      procedure and after the TAVI procedure at day 1 and day 4.

      The follow-up visit to 1 year will be conducted by cardiologists or cardiac surgeons with an
      evaluation of the cognitive function by the mini-mental state (MMS).
observational model: Cohort
time perspective: Prospective
measure: Pre-operative leukocyte DNA methylation rate
time frame: Within one week after the procedure
description: This rate will be measured by the LUMA method in patients treated with TAVI according to the presence of at least one new cerebral ischemic lesion and/or microbleeds cerebral lesion appearing on post-procedural MRI
measure: Variation of the leukocyte DNA methylation rate during the TAVI procedure
time frame: At time between the pre (day-1) and postprocedural (day 1) samples
description: This rate will be measured by the LINE-1 method in all patients
measure: Pre-operative leukocyte DNA methylation rate (stroke/TIA)
time frame: One day before the procedure and within one week after the procedure
description: This rate will be measured by the LUMA method in patients treated with TAVI according to the presence of a neurological deficit (stroke, transient ischemic attack)
measure: Mortality
time frame: At 1 year after procedure
description: The mortality in patients treated with TAVI according to the presence of at least one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion detected on postoperative cerebral MRI and / or postprocedural ischemic stroke / TIA
measure: MMSE score variation
time frame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
description: The MMSE score variation is compared according to the presence or not of at least one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion
measure: Change of EQ-5D questionnaire
time frame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
description: The evolution of quality of life is compared to the occurrence of new cerebral events one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion
measure: Change of modified Rankin Scale (mRS)
time frame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
description: The MRS (measure degree of disability- troke) is compared to the occurrence of new cerebral events one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion
measure: Change of National Institutes of Health Stroke Scale (NIHSS)
time frame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
description: TheNIHSS (quantify the impairment caused by a stroke) is compared to the occurrence of new cerebral events one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion
measure: Clinical and Biological predictors of new cerebral events
time frame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
description: The clinical (measured before the procedure) and biological characteristics of the patients (measured before the procedure and after the procedure) and of the peri-procedural parameters associated with the occurrence of new events detected on post-procedural MRI (new ischemic and/or new microbleeds cerebral lesion appearing on post-procedural MRI)
measure: Hemostasis predictors of new cerebral events
time frame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
description: Hemostasis parameters (measured before the procedure and after the procedure) including Willebrand factor parameters associated with the occurrence of new events detected on postoperative MRI (new ischemic and/or new microbleeds cerebral lesion)
measure: Number of complications in peri-procedural according to VARC-2 criteria
time frame: Within one week after the procedure
description: Evaluation of multi criteria according to the Valve academic Research Consortium (VARC-2)
arm group label: Cerebral Lesion
description: Patient over 70 years with severe aortic stenosis requiring percutaneous aortic valvular replacement (TAVI) having at least one new cerebral ischemic lesion on postoperative cerebral MRI
arm group label: No Cerebral Lesion
description: Patient over 70 years with severe aortic stenosis requiring percutaneous aortic valvular replacement (TAVI) with no cerebral ischemic lesion on postoperative cerebral MRI
arm group label: patients with constitutional von Willebrand factor (vWF) deficiency
We compare the pre-operative leukocyte DNA methylation rate measured by the Luminometric
      Methylation Assay (LUMA) method in patients treated with TAVI and patients with
      constitutional von Willebrand factor (vWF) deficiency according to the presence or absence of
      at least one new cerebral ischemic lesion detected on postoperative cerebral MRI.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: No
last name: Nicolas Debry, MD
role: Principal Investigator
affiliation: University Hospital, Lille
last name: Nicolas Debry, MD
phone: +33 3 20 44 59 62
phone ext: +33
email: nicolas.debry@chru-lille.fr
facility: 
status: Recruiting
investigator: 
country: France
citation: Ghanem A, Kocurek J, Sinning JM, Wagner M, Becker BV, Vogel M, Schroder T, Wolfsgruber S, Vasa-Nicotera M, Hammerstingl C, Schwab JO, Thomas D, Werner N, Grube E, Nickenig G, Muller A. Cognitive trajectory after transcatheter aortic valve implantation. Circ Cardiovasc Interv. 2013 Dec;6(6):615-24. doi: 10.1161/CIRCINTERVENTIONS.112.000429. Epub 2013 Oct 15.
PMID: 24129642
citation: Kahlert P, Knipp SC, Schlamann M, Thielmann M, Al-Rashid F, Weber M, Johansson U, Wendt D, Jakob HG, Forsting M, Sack S, Erbel R, Eggebrecht H. Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study. Circulation. 2010 Feb 23;121(7):870-8. doi: 10.1161/CIRCULATIONAHA.109.855866.
PMID: 20177005
citation: Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekstrom TJ, Harris TB, Launer LJ, Eiriksdottir G, Leppert MF, Sapienza C, Gudnason V, Feinberg AP. Intra-individual change over time in DNA methylation with familial clustering. JAMA. 2008 Jun 25;299(24):2877-83. doi: 10.1001/jama.299.24.2877.
PMID: 18577732
citation: Baccarelli A, Wright R, Bollati V, Litonjua A, Zanobetti A, Tarantini L, Sparrow D, Vokonas P, Schwartz J. Ischemic heart disease and stroke in relation to blood DNA methylation. Epidemiology. 2010 Nov;21(6):819-28. doi: 10.1097/EDE.0b013e3181f20457.
PMID: 20805753
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responsible party type: Sponsor
mesh term: Cognitive Dysfunction
sharing ipd: No