DNA Repair in Patients With Stable Angina.

Coronary Artery Disease Clinical Trial

— DECODE II  

Official title:

DNA Repair in Patients With Stable Angina.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04453267
• Other study ID #: CAR0566
• Status: Recruiting
• Start date: February 5, 2020
• Est. completion date: August 1, 2024

Study information

• Verified date: October 2022
• Source: University Hospital Southampton NHS Foundation Trust
• Contact: Thomas R Gilpin, MBBCh
• Phone: 0044 (0)2380777222
• Email: thomas.gilpin[@]uhs.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 172
• Est. completion date: August 1, 2024
• Est. primary completion date: August 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Angina, Stable
• Arteriosclerosis
• Coronary Arteriosclerosis
• Coronary Artery Disease
• DNA Damage
• DNA Repair Abnormality
• Myocardial Ischemia

Locations

Country	Name	City	State
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton	Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Southampton NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.