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DECODE II: DNA Repair in Patients With Stable Angina.

Sponsor
University Hospital Southampton NHS Foundation Trust (Other)
Overall Status
Unknown status
CT.gov ID
NCT04453267
Collaborator
(none)
172
Enrollment
1
Location
20.9
Anticipated Duration (Months)
8.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Markers of DNA damage and repair are present in both atherosclerotic plaques and peripheral blood mononuclear cells of patients with coronary artery disease. A positive correlation has been observed between the level of DNA damage and the severity of atherosclerotic lesions, as well as atherogenic risk factors such as smoking, hypertension and hyperlipidaemia. A number of in-vitro studies have implicated defective DNA repair in the development and progression of atherosclerotic lesions. In mouse models of atherosclerosis, the DNA repair signalling cascade has been shown to be amenable to pharmacological intervention and overexpression of specific repair proteins attenuate the development of atherosclerotic plaques. However, data regarding the role of DNA repair in the pathogenesis of atherosclerosis in humans are lacking. We have preliminary data indicating reduced DNA repair activity in patients with stable angina. This study will determine the molecular basis and the biological consequences of this observation.

Condition or Disease Intervention/Treatment Phase

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    172 participants
    Observational Model:
    Other
    Time Perspective:
    Prospective
    Official Title:
    DNA Repair in Patients With Stable Angina.
    Actual Study Start Date :
    Feb 5, 2020
    Anticipated Primary Completion Date :
    Nov 1, 2021
    Anticipated Study Completion Date :
    Nov 1, 2021

    Arms and Interventions

    Arm Intervention/Treatment
    Patient Arm.

    Consecutive patients undergoing elective percutaneous coronary intervention (PCI) or isolated coronary artery bypass grafting (CABG) for symptomatic stable angina (SA) despite optimal medical therapy at the University Hospital Southampton NHS Foundation Trust will be prospectively enrolled (n=86). No interventions administered. 40ml of whole blood in EDTA vials to be taken for cellular separation and analysis.
    Age and gender matched controls

    Age and gender-matched patients being investigated for chest pain with unobstructed coronary arteries, defined as coronary stenosis ≤ 30% in any major epicardial vessel on CT or invasive coronary angiography, will also be recruited as controls (n=86). 40ml of whole blood in EDTA vials to be taken for cellular separation and analysis.

    Outcome Measures

    Primary Outcome Measures

    1. Association between monocytes exhibiting reduced base excision repair and/or double strand break repair activity in patients with stable angina as compared to patients without coronary artery disease. [Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.]

      This will be assessed using real-time polymerase chain reaction, western blotting and proteosomal degradation assay.

    2. Reduced DNA repair activity is associated with impaired response to oxidative stress in human monocytes in patients with stable angina in comparison to an age and gender matched control. [Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Age ≥18 years

    • Ability to provide written informed consent

    Exclusion Criteria:

    • Age ≥ 80 years

    • Inability to provide written informed consent

    • Presentation with an acute coronary syndrome

    • Severe valvular heart disease

    • Hypertrophic cardiomyopathy

    • Left ventricular ejection fraction ≤ 35%

    • Prior coronary revascularisation (surgical or percutaneous)

    • Diabetes Mellitus

    • Clinical evidence of peripheral vascular disease

    • Prior history of cerebrovascular disease

    • Malignancy

    • Active inflammatory disorders (e.g. rheumatoid arthritis/connective tissue disorder)

    • Renal impairment eGFR <60ml/min/1.73m2

    • Anaemia (Hb <100g/dL)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital Southampton NHS Foundation Trust Southampton Hampshire United Kingdom SO16 6YD

    Sponsors and Collaborators

    • University Hospital Southampton NHS Foundation Trust

    Investigators

    • Principal Investigator: Michael Mahmoudi, MD,PhD, University Hospital Southampton NHS Foundation Trust

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University Hospital Southampton NHS Foundation Trust
    ClinicalTrials.gov Identifier:
    NCT04453267
    Other Study ID Numbers:
    • CAR0566
    First Posted:
    Jul 1, 2020
    Last Update Posted:
    Jul 1, 2020
    Last Verified:
    Jun 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Coronary Artery Disease
    Myocardial Ischemia
    Angina, Stable
    Arteriosclerosis

    Study Results

    No Results Posted as of Jul 1, 2020