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Mitochondrial Dysfunction Contributes to Sepsis Induced Cardiac Dysfunction

NCT05148117 · Status: WITHDRAWN · Type: OBSERVATIONAL

Last updated 2026-02-20

No results posted yet for this study

Summary

This proposal hypothesizes that mitochondrial bioenergetics in the patient will correspond to mtDNA DAMPs levels and markers of inflammation. We predict these will serve as a prognostic indicator of Sepsis induced cardiac dysfunction (SICD) outcomes. Successful completion of these studies will provide a clearer understanding of the etiology of SICD development and therefore will have a high impact on biomedical research by identifying a new mechanism for understanding sepsis induced organ failure. Importantly, they will also provide a means for more directed and focused therapies, based upon individual bioenergetic/mitochondrial-mediated inflammation profiles. The combined, complementary expertise of the Mentor/co-primary investigators (Drs. Mathru and Ballinger) provide an excellent combination in both basic and translational research. They also have experience conducting studies and publications that will strengthen this research project. Importantly, the methods for characterizing mitochondrial bioenergetics from platelets were developed here at UAB, and methods for quantitative assessment of mtDNA DAMPs have been recently developed.

Conditions

Interventions

DIAGNOSTIC_TEST

Suspected Sepsis Group - Diagnostic Measurements

Blood samples (7.5ml) will be collected in cell free DNA collection tubes cfDNA will be extracted with the use of MagMAX cell free DNA isolation kit. Quantitative PCR will determine the total cfDNA. cfDNA (5micro litr) will be subjected to bisulphide conversion with use of EZ DNA methylation kit (Zymo research). We will perform digital PCR for interrogating bisulphide treated cfDNA for FMA 101A locus with the use of Quant Studio 3D digital PCR system. Copy numbers of unmethylated FAM 101A locus as determined by d PCR in the sample will be expressed as the copy numbers of cardiomyocyte specific cfDNA per plasma volume.Inflammatory markers IL-6.IL-8, IL 1-18 and C-reactive protein (CRP) will be measured using commercial assays. Speckle tracking imaging will be used to obtain tissue displacement, velocity, strain, and strain rate in radial longitudinal and circumferential planes EF and FS will be determined by conventional methods.

DIAGNOSTIC_TEST

Control Group - Diagnostic Measurements

Blood samples (7.5ml) will be collected in cell free DNA collection tubes cfDNA will be extracted with the use of MagMAX cell free DNA isolation kit. Quantitative PCR will determine the total cfDNA. cfDNA (5micro litr) will be subjected to bisulphide conversion with use of EZ DNA methylation kit (Zymo research). We will perform digital PCR for interrogating bisulphide treated cfDNA for FMA 101A locus with the use of Quant Studio 3D digital PCR system. Copy numbers of unmethylated FAM 101A locus as determined by d PCR in the sample will be expressed as the copy numbers of cardiomyocyte specific cfDNA per plasma volume.Inflammatory markers IL-6.IL-8, IL 1-18 and C-reactive protein (CRP) will be measured using commercial assays. Speckle tracking imaging will be used to obtain tissue displacement, velocity, strain, and strain rate in radial longitudinal and circumferential planes EF and FS will be determined by conventional methods.

Sponsors & Collaborators

  • University of Alabama at Birmingham

    lead OTHER

Principal Investigators

  • Riaz Karukappadath, MD · Department of Anesthesiology and Perioperative Medicine, Division of Critical Care Medicine

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-12-10
Primary Completion
2026-01-14
Completion
2026-01-14

Countries

  • United States

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05148117 on ClinicalTrials.gov