Clinical trial NCT04453267: DNA Repair in Patients With Stable Angina.
Official title: DNA Repair in Patients With Stable Angina.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Artery Disease
Coronary Arteriosclerosis
DNA Damage
DNA Repair Abnormality
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
First posted: 2020-07-01
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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)

Primary outcomes:
measure: 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.
timeFrame: Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.
measure: 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.
timeFrame: Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.
Secondary outcomes:
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Michael Mahmoudi, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: