DNA Repair in Patients With Stable Angina.
DECODE II
1 other identifier
observational
172
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Feb 2020
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 5, 2020
CompletedFirst Submitted
Initial submission to the registry
June 26, 2020
CompletedFirst Posted
Study publicly available on registry
July 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2024
CompletedOctober 28, 2022
October 1, 2022
3.5 years
June 26, 2020
October 27, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
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.
This will be assessed using real-time polymerase chain reaction, western blotting and proteosomal degradation assay.
Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.
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.
Study Arms (2)
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.
Eligibility Criteria
Patients undergoing an assessment of thier coronary anatomy either by computerised tomography coronary angiogram or invasive coroanry angiogram at a large university teaching hospital performed as part of thier routine care.
You may qualify if:
- Age ≥18 years
- Ability to provide written informed consent
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, SO16 6YD, United Kingdom
Biospecimen
Stored samples of isolated T-Cells and Monocytes.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Mahmoudi, MD,PhD
University Hospital Southampton NHS Foundation Trust
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- OTHER
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 26, 2020
First Posted
July 1, 2020
Study Start
February 5, 2020
Primary Completion
August 1, 2023
Study Completion
August 1, 2024
Last Updated
October 28, 2022
Record last verified: 2022-10
Data Sharing
- IPD Sharing
- Will not share