Telomere Biology and AKI in Cardiac Surgery

September 18, 2017 updated by: Queen Mary University of London

Telomere Length and Telomerase Activity as a Predictor of Acute Kidney Injury Following Cardiac

The purpose of this study is to investigate whether biomarkers of cell senescence and aging can predict the development of acute kidney injury following cardiac surgery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients with pre-operative renal dysfunction are at increased risk of developing cardiac surgery associated acute kidney injury (AKI) but a proportion of patients with normal kidney function will also be affected. Studies show that patients developing AKI post cardiac surgery have a poorer long term prognosis, even if their kidney function subsequently returns to normal However, the cause for this is not currently understood. We postulate that a unifying mechanism makes such patients more susceptible to developing post-operative AKI and of having an overall worse long term prognosis. We suggest that this mechanism is reduced regenerative capacity of tissues. To test this hypothesis we will measure several markers of cell senescence and aging including telomere length, telomerase activity, and DNA methylation status.

Previous animal studies have shown that reduced telomere length and telomerase activity in mice increases their susceptibility to ischaemia induced renal injury. The current study will look at whether a similar association is seen in humans, using cardiopulmonary bypass as a mechanism for studying ischaemia/inflammatory induced kidney injury. It aims to answer the primary research question: Are telomere length and telomerase activity related to the development of acute kidney injury following cardiac surgery? The presence of such an association would provide new avenues in the development of biomarkers to predict outcomes following cardiac surgery. In addition to scoring tools currently in clinical practice, such biomarkers might allow better risk stratification of patients undergoing cardiac surgery.

Patient Registry and sample storage: Tissue samples and patient data collected in these patients will also form part of the Barts Cardiovascular Registry (BAR). This is a Biobank facility run by Barts Heart Centre in collaboration with United Kingdom (UK) Biobank. All aspects of patient recruitment, data collection, data storage, and data analysis will be covered by Standard Operating Procedures to ensure data quality of the registry.

Quality assurance: The management team for the BAR will be responsible for auditing the completeness and validity of the data.

Sample size: As we have no preceding data on a possible association with telomere biology and AKI post-cardiac surgery we have been unable to perform a power calculation for sample size. In effect, the present study will be a large pilot study looking at this association. Previously reported studies give an incidence of AKI following cardiac surgery of between 15 and 25%. In order to have approximately 200 AKI patients to study, we will aim to recruit 1000 patients. This is realistic given that the Barts Heart Centre should be performing approximately 50 cardiac operations per week. Once recruitment is established, an interim analysis will be performed to allow a more accurate estimation of sample size.

Statistical analysis: All relevant clinical parameters will be analysed by frequencies, tabulations, correlations, distributions of normality and comparisons accordingly. An array of statistical methods will be employed for parametric and non-parametric data including Multivariate of all factors associated with the development of acute kidney injury following cardiac surgery. Receiver operator characteristic (ROC) curve analysis will be used to investigate clinical outcomes and the new markers of cell senescence (telomere length, telomerase activity, and DNA methylation status). Missing data values will be rectified where possible by review of the primary medical records. Missing data values due to incomplete sample collection will be dealt with by statistical modelling.

Study Type

Observational

Enrollment (Actual)

254

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, EC1A 7BE
        • St Bartholomew's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All patients undergoing cardiac surgery

Description

Inclusion Criteria:

  • All adult patients undergoing cardiac surgery at Barts Heart Centre

Exclusion Criteria:

  • Renal dialysis patients
  • Renal transplant patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
AKI Patients
Patients who develop acute kidney injury within the first 5 days following their cardiac surgical operation.
Other: No intervention
No intervention. This is an observational study of how patients' renal function responds to their surgery. The groups are defined by this response. There is no difference between clinical interventions between the two groups.
Non-AKI patients
Patients who do not develop acute kidney injury within the first 5 days following their cardiac surgical operation.
Other: No intervention
No intervention. This is an observational study of how patients' renal function responds to their surgery. The groups are defined by this response. There is no difference between clinical interventions between the two groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Kidney Injury
Time Frame: 5 days
The development of acute kidney injury in the first 5 days of surgery.
5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
In hospital mortality
Time Frame: 30 days
All cause death during the post-operative hospital stay or within 30 days whichever is sooner.
30 days
Major adverse cardiac and cerebrovascular events
Time Frame: 30 days
Covers several outcomes within the index hospital admission of within 30 days whichever is shorter. The included outcomes are: Cardiac related mortality, stroke, myocardial infarction, and need for repeat revascularisation.
30 days
length of stay
Time Frame: Will be assessed upon patient's discharge from hospital. Typically 5-10 days but variable
length of in-hospital stay
Will be assessed upon patient's discharge from hospital. Typically 5-10 days but variable

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Queen Mary University of London

Collaborators

Barts & The London NHS Trust

Investigators

  • Study Director: Magdi M Yaqoob, PhD, Queen mary Univerisity of London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (Actual)

May 1, 2017

Study Completion (Actual)

May 1, 2017

Study Registration Dates

First Submitted

January 22, 2016

First Submitted That Met QC Criteria

February 22, 2016

First Posted (Estimate)

February 26, 2016

Study Record Updates

Last Update Posted (Actual)

September 20, 2017

Last Update Submitted That Met QC Criteria

September 18, 2017

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 010706

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We do not plan to share individual participant data outside of our research group

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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