DNA Damage & Repair Proteins In Patients With Atherosclerotic Coronary Artery Disease

NCT02335086 | Completed

• 1 other identifier: 13/LO/0238
• Study Type: observational
• Target: 126
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is:

1. 1.To examine the association between stable and unstable coronary artery disease (CAD) with markers of DNA damage and repair,
2. 2.To examine the association between plaque morphology as assessed by frequency-domain optical coherence tomography (FD-OCT) and markers of DNA damage and repair in order to identify potential markers of plaque instability,
3. 3.To examine the association between markers of DNA damage and repair and major adverse cardiovascular events defined as death, MI and unplanned percutaneous or surgical revascularization,

Conditions

Coronary Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Difference in DNA ligase activity in peripheral blood mononuclear cells of patients with stable angina and non-ST-elevation myocardial infarction

  DNA ligase (DNA repair enzyme) activity measured using units per well, in peripheral mononuclear cells between stable and NSTEMI patients undergoing percutaneous coronary intervention.

  18 months

Secondary Outcomes (1)

• Plaque fibrous cap thickness and its association with major adverse cardiovascular events (MACE)

  18 months

Study Arms (2)

Stable angina patients

Patients with stable angina not responding to 2 anti-anginals presenting for coronary angiography with the possibility of proceeding to stent implantation at Ashford and St. Peter's Hospital. Clinical and angiographic exclusion criteria as stated in the study protocol.

NSTEMI patients

Patients presenting to Ashford and St. Peter's Hospital with an non ST-elevation myocardial infarction defined by : Detection of a rise and/or fall of cardiac biomarker values (troponin I) with at least one value above the 99th percentile upper reference limit at analysing laboratories at Ashford and St. Peter's Hospital along with at least one of the following: * Symptoms of ischaemia * Development of pathologic Q waves in the electrocardiogram (ECG) * New or presumed new significant ST-segment-T wave (ST-T) changes on ECG. * Identification of an intracoronary thrombus by angiography. * Imaging evidence of new loss of viable myocardium or a new regional wall motion abnormality.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients presenting with stable angina (n=50) or NSTEMI (n=50) undergoing percutaneous revascularization at Ashford and St. Peter's Hospitals Foundation Trust will be prospectively enrolled. Data regarding demographic, clinical, and procedural characteristics of patients will be collected by the Ashford and St. Peter's Hospitals Foundation Trust research personnel and entered into a secure, dedicated database. Results will be compared to age and sex matched controls

You may qualify if:

• \-----------------------
• Clinical:
• Age ≥ 18 years
• Stable angina not responding to at least two anti-anginal medications (beta blockers, calcium channel antagonists, long acting nitrate, Nicorandil, Ivabradine, or Ranolazine), or NSTEMI.
• Patient is able to provide written, informed consent and is able to follow protocol procedures.
• Angiographic:
• \. Successful and uncomplicated percutaneous coronary intervention (PCI) performed in the major epicardial coronary arteries.
• NB: Successful PCI is defined as residual diameter stenosis \< 5% in all treated lesions with thrombolysis in myocardial infarction (TIMI)-3 flow (defined as normal flow which fills the distal coronary bed completely), absence of intraprocedural chest pain or ST-segment changes lasting \> 10 minutes, persistent vessel closure, no re-flow, perforation, dissection or requirement for cardiopulmonary resuscitation, defibrillation, pacemaker or intra-aortic balloon implantation.

You may not qualify if:

• \------------------------
• Clinical:
• Presentation with ST-elevation MI (STEMI),
• Decompensated heart failure, hypotension, shock, refractory ventricular tachycardia, acute conduction disorders, left ventricular ejection fraction ≤ 30%,
• Prior coronary revascularization,
• Any form of surgery up to three months prior to enrolment,
• Active inflammatory disorders,
• Bleeding diathesis,
• Known allergy, hypersensitivity, or contraindication to aspirin, heparin, or thienopyridines,
• Life expectancy less than 1 year,
• Diabetes mellitus.
• Angiographic:
• Left main coronary artery stenosis ≥ 50%,
• Coronary artery bypass surgery planned within one year of the PCI,
• Anatomical conditions precluding three-vessel FD-OCT (significant tortuosity, severe calcification, chronic total occlusion).

Sponsors & Collaborators

• University of Surrey: lead
• Ashford and St. Peter's NHS Trust: collaborator

Study Sites (2)

Ashford and St. Peter's Hospital

Chertsey, Surrey, KT16 0PZ, United Kingdom

Location

University of Surrey

Guildford, Surrey, GU2 7XH, United Kingdom

Location

Related Publications (2)

• Dan K, Garcia-Garcia HM, Yacob O, Kuku KO, Kolm P, Shah N, Bennett MR, Curzen N, Waksman R, Mahmoudi M. Comparison of plaque distribution and wire-free functional assessment in patients with stable angina and non-ST elevation myocardial infarction: an optical coherence tomography and quantitative flow ratio study. Coron Artery Dis. 2021 Mar 1;32(2):131-137. doi: 10.1097/MCA.0000000000000944.

  PMID: 32826449 DERIVED

• Shah N, Meira LB, Elliott RM, Hoole SP, West NE, Brown AJ, Bennett MR, Garcia-Garcia HM, Kuku KO, Dan K, Kolm P, Mariathas M, Curzen N, Mahmoudi M. DNA Damage and Repair in Patients With Coronary Artery Disease: Correlation With Plaque Morphology Using Optical Coherence Tomography (DECODE Study). Cardiovasc Revasc Med. 2019 Sep;20(9):812-818. doi: 10.1016/j.carrev.2019.04.028. Epub 2019 May 23.

  PMID: 31178349 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, serum, white blood cells

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: January 9, 2015
• Study Start: September 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: February 23, 2017

Record last verified: 2017-02

Locations

GB (2)