DNA Repair in Patients With Stable Angina. (DECODE II)

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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Coronary Arteriosclerosis; DNA Damage; DNA Repair Abnormality

• Study Type: Observational
• Enrollment (Anticipated): 172

Contacts and Locations

• Study Contact: Name: Thomas R Gilpin, MBBCh; Phone Number: 3912 0044 (0)2380777222; Email: thomas.gilpin@uhs.nhs.uk
• Study Contact Backup: Name: Zoe Nicholas, BSc; Phone Number: 8538 0044 (0)2380777222; Email: zoe.nicholas@uhs.nhs.uk

Study Locations

• United Kingdom
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Recruiting
      • University Hospital Southampton NHS Foundation Trust
      • Contact: Michael Mahmoudi, MD,PhD; Phone Number: 8538 0044 (0)23801208538; Email: michael.mahmoudi@uhs.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: University Hospital Southampton NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 5, 2020
• Primary Completion (ANTICIPATED): August 1, 2023
• Study Completion (ANTICIPATED): August 1, 2024

Study Registration Dates

• First Submitted: June 26, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (ACTUAL): July 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Coronary Disease; Chest Pain; Angina Pectoris; Coronary Artery Disease; Myocardial Ischemia; Arteriosclerosis; Angina, Stable
• Other Study ID Numbers: CAR0566

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No