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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 (Ob-Card)

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ClinicalTrials.gov Identifier: NCT02908009
Recruitment Status : Recruiting
First Posted : September 20, 2016
Last Update Posted : January 30, 2020
Sponsor:
Information provided by (Responsible Party):
University of Leicester

Brief Summary:
This is a prospective, single-center case control comparison of expression of target genes responsible for energy utilization, mitochondrial function and oxidative stress and levels of histone acetylation/ DNA methylation in obese and non-obese adult cardiac surgery patients.

Condition or disease
C.Surgical Procedure; Cardiac

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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Case-Control
Time Perspective: Prospective
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
Actual Study Start Date : September 9, 2016
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Post surgery inotrope score [ Time Frame: inotrope score measured up to 48 hours post-surgery ]
    inotrope score measured up to 48 hours post-surgery


Secondary Outcome Measures :
  1. The vasoactive-inotrope score measured up to 48 hours post-surgery [ Time Frame: inotrope score measured up to 48 hours post-surgery 48 hours ]
  2. Changes in expression of target genes from left atrial biopsies [ Time Frame: At the time of surgery ]
  3. Changes in epigenetic regulation (histone acetylation, DNA methylation) of target genes from left atrial biopsies. [ Time Frame: At the time of surgery ]
  4. Myocardial Injury defined by post cardiac surgery serum Troponin levels [ Time Frame: baseline and 24 hours ]
  5. Acute kidney injury defined by serum creatinine level postoperatively, as per the KDIGO criteria [ Time Frame: baseline, and up to 15 days post surgery (discharge) ]
  6. Data on weight in kilograms [ Time Frame: pre op ]
  7. Data on height in meters [ Time Frame: pre op ]
  8. Data on age [ Time Frame: Pre op ]
  9. Data on gender [ Time Frame: Pre op ]
  10. Data on race [ Time Frame: Pre op ]
  11. Data on pulmonary function expressed as partial pressure of oxygen (PaO2) [ Time Frame: baseline, and up to 15 days post surgery (discharge) ]
  12. Data on fraction of inspired oxygen (FiO2) (i.e. the amount of oxygen a patient is inhaling) [ Time Frame: baseline, and up to 15 days post surgery (discharge) ]
  13. Data on length of hospital and ICU stay [ Time Frame: baseline, and up to 15 days post surgery (discharge) ]
  14. Data to calculate Multiple Organ Dysfunction (MOD) score [ Time Frame: baseline, and up to 96 hours post surgery ]

    To calculate the MOD score, the Respiratory Function (calculated as partial pressure of oxygen (PaO2) divided by fraction of inspired oxygen (FiO2)), Cardiovascular (Pressure adjusted heart rate (PAR) ), Renal (Serum Creatinine), Hepatic (serum bilirubin), Hematologic (platelet count) and neurologic (Glasgow Coma Score (GCS)) organ function need to be recorded at the following time points in the Case Report Form (CRF):

    • Pre-OP
    • ICU
    • 12 hours post-op
    • 24 hours post-op
    • 48 hours post-op
    • 72 hours post-op
    • 96 hours post-op

  15. Data to capture Acute Respiratory Distress Syndrome [ Time Frame: baseline, and up to 96 hours post surgery ]
    Acute Lung Injury (ALI) non-ARDS, ARDS. To define these different categories of acute lung injury, the Positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) will be recorded in the CRF at time points: Pre-OP, ICU, 12 hrs post-op,24hrs post-op,48hrs post-op,72hrs post-op and 96hrs post-op. Along with the PaO2/FiO2 ratio, it will then be possible to categorise patients into the above definitions of acute lung injury as follows: ALI non-ARDS (200 mmHg <PaO2/FiO2<300 mmHg, regardless of PEEP),ARDS (PaO2/FiO2<200 mmHg, regardless of PEEP), mild Berlin Definition(200mmHg <PaO2/FiO2<300mmHg with PEEP > 5cm H2O),moderate Berlin Definition(100mmHg <calculated as partial pressure of oxygen divided by fraction of inspired oxygen PaO2/FiO2 < 200mmHg with PEEP > 5cm H2O) and Severe Berlin Definition (PaO2/FiO2 < 100mmHg with PEEP > 5cm H2O)

  16. Inotrope Score [ Time Frame: baseline, and up to 15 days post surgery (discharge) ]
    This is calculated as the sum of the maximum dopamine dose (µg/kg/min), the maximum dobutamine dose (µg/kg/min) and the maximum adrenaline dose (µg/kg/min).

  17. Vasoactive inotrope score [ Time Frame: baseline, and up to 15 days post surgery (discharge) ]
    This is calculated as the sum of the Inotrope Score plus the sum of (10 x milrinone dose (µg/kg/min)), (10,000 x maximum vasopressin dose U/kg/min) and (100 x maximum norepinephrine dose (µg/kg/min)).


Biospecimen Retention:   Samples With DNA
Atrial Biopsy: A 0.5cm x 0.5cm section of the right atrial wall is routinely excised to allow cannulation of the left atrium for connection to the cardiopulmonary bypass machine. This segment is routinely discarded. We propose to collect this specimen immediately after it has been discarded.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02908009


Contacts
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Contact: Tracy Kumar 01162583039 tk98@leicester.ac.uk

Locations
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United Kingdom
England Recruiting
Glenfield, Leicestershire, United Kingdom, LE3 9QP
Sponsors and Collaborators
University of Leicester
Investigators
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Principal Investigator: Gavin Murphy University of Leicester
Principal Investigator: Filiberto Serraino University of Leicester
Publications:
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Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT02908009    
Other Study ID Numbers: 0574
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: January 30, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight