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Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly (METHYSTROKE)

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ClinicalTrials.gov Identifier: NCT02972008
Recruitment Status : Recruiting
First Posted : November 23, 2016
Last Update Posted : May 16, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille

Brief Summary:

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.


Condition or disease
Cognitive Decline Stroke

Detailed Description:

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).


Study Type : Observational
Estimated Enrollment : 542 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly
Actual Study Start Date : March 9, 2017
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine


Group/Cohort
Cerebral Lesion
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
No Cerebral Lesion
Patient over 70 years with severe aortic stenosis requiring percutaneous aortic valvular replacement (TAVI) with no cerebral ischemic lesion on postoperative cerebral MRI



Primary Outcome Measures :
  1. Pre-operative leukocyte DNA methylation rate (cerebral lesions) [ Time Frame: The day before the TAVI procedure ]
    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 on postoperative MRI


Secondary Outcome Measures :
  1. 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 ]
    This rate will be measured by the LINE-1 method in all patients

  2. Pre-operative leukocyte DNA methylation rate (stroke/TIA) [ Time Frame: The day before the TAVI procedure ]
    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)

  3. Mortality [ Time Frame: At 1 year after TAVI procedure ]
    The mortality in patients treated with TAVI according to the presence of at least one new ischemic cerebral lesion detected on postoperative cerebral MRI and / or postprocedural ischemic stroke / TIA

  4. MMS score variation [ Time Frame: At day-1 before TAVI procedure and at 1 year after TAVI procedure ]
    The MMS score variation is compared according to the presence or not of at least one new cerebral ischemic lesion


Biospecimen Retention:   Samples With DNA
We compare the pre-operative leukocyte DNA methylation rate measured by the Luminometric Methylation Assay (LUMA) method in patients treated with TAVI according to the presence or absence of at least one new cerebral ischemic lesion detected on postoperative cerebral MRI.


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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients over 70 years with severe aortic stenosis requiring percutaneous aortic valve replacement (TAVI)
Criteria

Inclusion Criteria:

  • Patients over 70 years with severe aortic stenosis requiring percutaneous aortic valve replacement (TAVI)

Exclusion Criteria:

  • Patient contraindicated for the TAVI procedure
  • Patient with a pace-maker
  • Patient with contra-indication for cerebral MRI
  • Ongoing cancer
  • Patient already involved in therapeutic research
  • Major persons under protection of justice.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02972008


Contacts
Contact: Nicolas Debry, MD +33 3 20 44 59 62 ext +33 nicolas.debry@chru-lille.fr

Locations
France
Hôpital cardiologie, CHRU Recruiting
Lille, France
Principal Investigator: Nicolas Debry, MD         
Sponsors and Collaborators
University Hospital, Lille
Investigators
Principal Investigator: Nicolas Debry, MD University Hospital, Lille

Publications:

Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT02972008     History of Changes
Other Study ID Numbers: 2015_92
2016-A01035-46 ( Other Identifier: ID-RCB number )
PHRCI_2015 ( Other Identifier: PHRC number,DGOS )
First Posted: November 23, 2016    Key Record Dates
Last Update Posted: May 16, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Lille:
Aortic stenosis
Transaortic valve replacement
stroke
Epigenetic

Additional relevant MeSH terms:
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders