Clinical trial NCT02908009: A Case Control Study to Identify the Role of Epigenetic Regulation of Genes Responsible for Energy Metabolism and Mitochondrial Function in the Obesity Paradox in Cardiac Surgery
Official title: An Observational Case Control Study to Identify the Role of Epigenetic Regulation of Genes Responsible for Energy Metabolism and Mitochondrial Function in the Obesity Paradox in Cardiac Surgery
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: C.Surgical Procedure; Cardiac
Lead sponsor: University of Leicester
Sponsor class: OTHER
First posted: 2016-09-20
Enrollment: 80
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will be carried out at a large tertiary academic cardiac surgery unit in the UK; the University Hospitals of Leicester NHS Trust. This unit performs over 1,200 major cardiac procedures per year, of which 600 are patients undergoing coronary artery bypass grafting

Brief summary: This is a prospective, single-centre case control comparison of expression of target genes responsible for energy utilisation, mitochondrial function and oxidative stress and levels of histone acetylation/ DNA methylation in obese and non-obese adult cardiac surgery patients. The study aims to test several inter-related hypotheses in a consecutive sequence of patients undergoing coronary artery bypass grafting.


Eligibility criteria: Inclusion Criteria:

* Patients with pre-existing paroxysmal, persistent or chronic atrial fibrillation,

Exclusion Criteria:

* Patients with pre-existing inflammatory state: sepsis undergoing treatment, acute kidney injury within 5 days, chronic inflammatory disease, congestive heart failure.
* Emergency or salvage procedure.
* Ejection fraction \<30 %.
* Patient in a critical preoperative state (Kidney Disease: Improving Global Outcomes (KDIGO) Stage 3 AKI \[20\] or requiring inotropes, ventilation or intra-aortic balloon pump).
* Pregnancy.

Primary outcomes:
measure: Post surgery inotrope score
timeFrame: inotrope score measured up to 48 hours post-surgery
Secondary outcomes:
measure: Changes in expression of target genes
timeFrame: Collected at the time of surgery
measure: Changes in epigenetic regulation of target genes from left atrial biopsies.
timeFrame: Collected at the time of surgery
measure: Changes in mitochondrial function
timeFrame: before and after sugery (up to 12 hours post surgery)
measure: Myocardial Injury
timeFrame: baseline and 24 hours
measure: Acute kidney injury
timeFrame: baseline, and up to 15 days post surgery (discharge)
measure: Perioperative clinical characteristics
timeFrame: Collected pre op
measure: Perioperative medications.
timeFrame: Collected pre op
measure: Data to calculate Multiple Organ Dysfunction (MOD) score.
timeFrame: baseline, and up to 96 hours post surgery
measure: Data to capture Acute Respiratory Distress Syndrome (Berlin criteria ARDS).
timeFrame: baseline, and up to 96 hours post surgery
measure: Data on demographics
timeFrame: Pre Op
measure: Data on demographics
timeFrame: Pre Op
Other outcomes:
Locations:
city: Glenfield
country: United Kingdom
facility: England
state: Leicestershire
Study officials:
affiliation: University of Leicester
name: Gavin Murphy
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Leicester
name: Filiberto Serraino
role: PRINCIPAL_INVESTIGATOR
References:
citation: ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
citation: Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995 Oct;23(10):1638-52. doi: 10.1097/00003246-199510000-00007.
citation: Adebayo AS, Roman M, Zakkar M, Yusoff S, Gulston M, Joel-David L, Anthony B, Lai FY, Murgia A, Eagle-Hemming B, Sheikh S, Kumar T, Aujla H, Dott W, Griffin JL, Murphy GJ, Wozniak MJ. Gene and metabolite expression dependence on body mass index in human myocardium. Sci Rep. 2022 Jan 26;12(1):1425. doi: 10.1038/s41598-022-05562-8.