Novel Cardiovascular Biomarkers in Patients With Kidney Disease (CBKD)

September 14, 2023 updated by: Liverpool University Hospitals NHS Foundation Trust

Chronic kidney disease (CKD) is a long-term condition where the kidneys do not work as well as they should. End-stage kidney failure (ESKD) is the final, irreparable stage of chronic kidney disease (CKD), where kidney function has worsened, so the kidneys can no longer function independently.

At this stage, dialysis is required to remove waste products and excess fluid from the blood. There are two types of dialysis. In haemodialysis (HD), blood is pumped out of the body to an artificial kidney machine and returned to the body by tubes that connect a person to the machine. In peritoneal dialysis (PD), the inside lining of the belly acts as a natural filter. PD has the advantage of being gentler on the heart. HD causes significant stress to the heart by reducing the blood flow to the heart muscle, resulting in heart failure, irregular rhythms, and eventually sudden heart death. A large observational study showed that HD patients had 48% worse survival in the first two years than PD patients.

Several molecules ('biomarkers') can be detected in blood and inform doctors of heart damage. Studying the form and function of proteins (Proteomics), including how they work and interact with each other inside cells in patients, could help identify the onset of heart problems. HD patients are also prone to body fat changes (cholesterol/lipids). Due to high cholesterol, there is build-up on the walls of arteries, causing their hardening. In HD patients, this process is faster due to abnormalities in lipid structure. Therefore, studying the heart biomarkers, protein, and lipid makeup of HD patients may help to find people at substantial risk of heart and vascular problems and if they are likely to become unwell due to these heart problems.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Currently, there is no specific approach to stratify CV risk in HD patients; therefore, patients are not offered targeted preventative interventions. This novel project will characterise circulating biomarkers and proteomics of myocyte damage, cardiac stress, fibrosis, and inflammation, including lipid composition. Understanding the cardiac biomarkers, targeted proteomics and lipidomics in HD patients as early predictors of CV outcomes will help better decisions on treatment choices and earlier interventions to improve outcomes in these patients. Proteomics and lipidomics, analysed with machine learning techniques, may offer new opportunities to improve risk stratification in these patients. The successful introduction of novel agents, comprising proprotein convertase subtilisin-like/kexin type 9 inhibitors, low-dose oral anticoagulants, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 agonists, anti-inflammatory agents, and icosapent ethyl, offers an opportunity to reduce the burden of recurrent CV risk further based on their risk stratification. This study aims to obtain pilot data for promising cardiac biomarkers, proteomics and lipidomics, validating them against control groups and establishing prospective changes of the new markers and their relation to the major adverse cardiac events (MACE).

Study Objectives

  1. To determine circulating plasma levels of new cardiac biomarkers (cMyC, galectin 3) in incident HD patients by comparing them to control groups (PD and CKD 3-4 (not on dialysis)) and to correlate with traditional biomarkers (hsTnT).
  2. To evaluate the lipidome as a marker of CVD risk in incident HD patients by studying the indices of HDL quality and quantity, including HDL-particle number, HDL cholesterol, apolipoprotein (apo) A-I levels, serum amyloid A (SAA) content and HDL-cholesterol efflux capacity, and paraoxonase activity of apoB-depleted serum.
  3. To evaluate proteomic signature as a marker of cardiac disease risk in incident HD patients by studying the proteomic platform of untargeted high-value proteins for CVD risk (as an exploratory analysis).
  4. To explore the association between proposed cardiac biomarkers, proteomics, lipidome and MACE (as an exploratory analysis).

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

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

Study Contact

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Adults aged ≥45 years (or ≥18 with a history of diabetes) for both cases and controls. Cardiovascular risk steeply increases after the age of 45 years. For this exploratory analysis, we intend to target patients at high risk of cardiovascular disease.

Description

Inclusion Criteria:

Patients aged≥45 years (or ≥18 with a history of diabetes). b. Cases: Incident haemodialysis patients c. A comparative arm of peritoneal dialysis patients and CKD 3-4 (not on dialysis) with hypertension as a key risk factor for CVD.

d. Capable of understanding the purpose and risks of the study, fully informed, and given informed consent.

Exclusion Criteria:

  1. Patients with pre-existing heart disease will be excluded.
  2. Patients with active cancer.

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
Cases (N=50):
Patients with incident ESKD managed by HD (n=50)
Diagnostic test: Cardiac Biomarkers
Blood samples will be collected at baseline (within 6 weeks of dialysis start), at 6 months post-commencement and 12 months post-commencement of haemodialysis. The blood sampling will be mid-week samples taken at the dialysis start for haemodialysis patients, with a similar approach for the PD controls. For the CKD controls, the blood samples will be scheduled around routine clinic attendance, adhering where possible to the time intervals for HD cases and PD controls.
Diagnostic test: Lipidomics
Blood samples will be collected at baseline (within 6 weeks of dialysis start), at 6 months post-commencement and 12 months post-commencement of haemodialysis. The blood sampling will be mid-week samples taken at the dialysis start for haemodialysis patients, with a similar approach for the PD controls. For the CKD controls, the blood samples will be scheduled around routine clinic attendance, adhering where possible to the time intervals for HD cases and PD controls.
Diagnostic test: Proteomics
Blood samples will be collected at baseline (within 6 weeks of dialysis start), at 6 months post-commencement and 12 months post-commencement of haemodialysis. The blood sampling will be mid-week samples taken at the dialysis start for haemodialysis patients, with a similar approach for the PD controls. For the CKD controls, the blood samples will be scheduled around routine clinic attendance, adhering where possible to the time intervals for HD cases and PD controls.
Controls (N=50)
Patients with Incident ESKD managed by PD (n=20) Patients with CKD stage 3-4 (not on dialysis) with hypertension as a key risk factor for CKD and CVD (n=30)
Diagnostic test: Cardiac Biomarkers
Blood samples will be collected at baseline (within 6 weeks of dialysis start), at 6 months post-commencement and 12 months post-commencement of haemodialysis. The blood sampling will be mid-week samples taken at the dialysis start for haemodialysis patients, with a similar approach for the PD controls. For the CKD controls, the blood samples will be scheduled around routine clinic attendance, adhering where possible to the time intervals for HD cases and PD controls.
Diagnostic test: Lipidomics
Blood samples will be collected at baseline (within 6 weeks of dialysis start), at 6 months post-commencement and 12 months post-commencement of haemodialysis. The blood sampling will be mid-week samples taken at the dialysis start for haemodialysis patients, with a similar approach for the PD controls. For the CKD controls, the blood samples will be scheduled around routine clinic attendance, adhering where possible to the time intervals for HD cases and PD controls.
Diagnostic test: Proteomics
Blood samples will be collected at baseline (within 6 weeks of dialysis start), at 6 months post-commencement and 12 months post-commencement of haemodialysis. The blood sampling will be mid-week samples taken at the dialysis start for haemodialysis patients, with a similar approach for the PD controls. For the CKD controls, the blood samples will be scheduled around routine clinic attendance, adhering where possible to the time intervals for HD cases and PD controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Adverse Cardiac Events
Time Frame: 12 months
An exploratory analysis of all-cause mortality and Major Adverse Cardiac Events (MACE). MACE is defined as a composite of CV death, Ischemic Heart Disease (IHD), myocardial infarction (MI), stroke/TIA, Heart Failure, Cardiac revascularisation (percutaneous coronary intervention and coronary artery bypass graft), carotid endarterectomy. The follow-up will be 12 months for all patients. This will be correlated with biomarker, proteomic and lipidomic data.
12 months

Collaborators and Investigators

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

Sponsor

Liverpool University Hospitals NHS Foundation Trust

Investigators

  • Principal Investigator: Anirudh Rao, PhD, Liverpool University Hospital NHS Trust

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 (Estimated)

November 1, 2023

Primary Completion (Estimated)

November 1, 2025

Study Completion (Estimated)

November 1, 2026

Study Registration Dates

First Submitted

September 7, 2023

First Submitted That Met QC Criteria

September 7, 2023

First Posted (Actual)

September 14, 2023

Study Record Updates

Last Update Posted (Actual)

September 18, 2023

Last Update Submitted That Met QC Criteria

September 14, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LHS0082

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

However, the samples will be bio-banked at Liverpool University Biobank which can be shared with researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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