Age Related Chromatin Remodelling as a Therapeutic Target for Organ Protection in Cardiac Surgery

NCT07389785 | Active Not Recruiting

• 2 other identifiers: 1086356697
• Study Type: observational
• Target: 3,055
• Locations: 1 country
• Sites: 1

Brief Summary

People who have multiple long-term conditions (MLTC) like kidney disease or lung disease are at higher risk of developing organ damage and poor quality of life following heart surgery. Decades of research have failed to identify drugs or treatments that prevent this. Our research has shown that people with MLTC have changes in their heart cells before surgery that are referred to by researchers as Biological Ageing. These changes combine to make people with MLTC more susceptible to organ damage after heart surgery, have delayed recovery, and lower quality of life. This research programme will investigate the processes linking MLTC, changes in heart cells, and organ damage. Our previous research suggests that MLTC lead to the infiltration of white cells from the blood into the heart muscle, a process called inflammageing. This alters the DNA in heart cells, reduces their pumping function and leaves them more likely to be damaged by surgery. We have also shown that these changes are affected by obesity. We have also shown that changes in other types of heart cells with ageing are associated with damage to the lining of blood vessels, bleeding and damage to the kidneys. We will use existing clinical data from previous studies and molecular data from heart cells obtained at surgery to better understand the molecular changes underlying our previous observations. This includes data from previous trials of drugs and dietary modification that aimed to modify the cellular DNA changes caused by inflammageing. Using external data, we will check whether similar results are evident in other studies. We will then select the most likely processes underlying our observations and test whether these relationships are causal using genomic analysis and the UK Biobank data. Finally, we will use established analytical methods to identify potential drugs that may target these processes. Positive results will provide a better understanding of the heart damage that is often seen in people with MLTC as well as new treatments for evaluation on further research.

Conditions

Cardiac Surgery; Organ Protection; Ageing

Keywords

chromatin; cardiac surgery; organ protection; multiple long-term conditions; ageing

Outcome Measures

Primary Outcomes (10)

• Study 1

  For the clinical studies, outcomes will be restricted to those measured prospectively in the individual studies. For the UK Biobank data, the primary outcome is time to death or emergency re-hospitalisation requiring overnight admission within 365 days following discharge after major surgery.

  5 years

• Study 2

  The analysis will identify differentially expressed genes, gene pathways, and networks in cell types by phenotype. The data will also identify differences in promoter accessibility by cell type and phenotype

  5 years

• Study 3

  These studies will provide quantitative targeted validation of genes, proteins and DNA accessibility by cell type and phenotype in human myocardial biopsies obtained at surgery in the listed studies. We will identify anonymised publicly available external data sources that have evaluated biological ageing and inflammageing in human tissues. We will duplicate our primary genomics analysis in this secondary dataset.

  5 years

• Study 4

  We will quantify the effects of genetic modification of key genes and pathways identified in Studies 1-3 on mortality and freedom from hospitalisation in UK Biobank.

  5 years

• Study 5

  Clinical outcomes: Area under the troponin curve from baseline to 48 hours post-surgery.

  48 hours post-operation

• Study 5

  Clinical outcomes: Area under the creatinine curve from baseline to 72 hours post-surgery.

  72 hours post-operation

• Study 5

  Process outcomes: Valproate exposure

  6 weeks

• Study 5

  Process outcomes: Calorific intake

  6 weeks

• Study 5

  Process outcomes: Weight gain.

  6 weeks

• Study 5

  Experimental Outcomes: Combined snRNAseq/ ATACseq in myocardial biopsies (5 per group) obtained at surgery.

  1 day (operation day)

Study Arms (7)

MARACAS

Prospective, single-centre observational case-control study.

Other: other

REDWASH

A multicenter parallel-group randomized controlled trial.

Other: other

REVAKI-2

Phase IIB placebo-controlled randomised clinical trial.

Other: other

OB-CARD

Prospective, single-centre case control study.

Other: other

COPTIC-2

Retrospective, single-centre observational cohort trial.

Other: other

VAL-CARD

Single-centre, unblinded, randomised controlled trial (Phase 2b).

Other: other

PRE-OP ENERGY

Single-centre, unblinded, parallel group, randomised controlled trial.

Other: other

Interventions

other OTHER

This is not an interventional study.

COPTIC-2; MARACAS; OB-CARD; PRE-OP ENERGY; REDWASH; REVAKI-2; VAL-CARD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult cardiac surgery patients.

You may qualify if:

• Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) enrolled in seven clinical studies in five UK centres.

You may not qualify if:

• Patients who did not consent to participate in the included trials, or participants who did not consent for secondary research of their data and samples.

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (1)

University of Leicester

Leicester, Leicester, LE1 7RH, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood, biopsies (right atrial, vascular, adipose tissue and bone marrow).

Study Officials

• Gavin J Murphy, BSc, MBChB, FRCS, MD, FRCS CTh

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 17, 2025
• First Posted: February 5, 2026
• Study Start: September 29, 2025
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030
• Last Updated: February 5, 2026

Record last verified: 2026-01

Locations

GB (1)