Prognostic Value of Plasma Mitochondrial DNA and Cytochrome C After Cardiac Arrest

NCT ID: NCT03539497

Last Updated: 2023-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

87 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-01-08

Study Completion Date

2024-03-30

Brief Summary

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The aim of the study is to determine prognostic value of plasma mitochondrial DNA and cytochrome C after cardiac arrest.

The study will be conducted in three parts:

1. Determine plasma concentrations of mitochondrial DNA and cytochrome C in healthy population.
2. Determine release profile of mitochondrial DNA and cytochrome C to plasma after cardiac arrest.
3. Determine plasma prognostic value of mitochondrial DNA and cytochrome C after cardiac arrest and compare it with established prognostic methods.

Detailed Description

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Scientific background

Cardiac arrest is one of leading causes of mortality in developed world. Survival ranges between 15 and 22%. Patients surviving cardiac arrest can have significant neurological impairment. None of currently available diagnostic methods can detect neurological consequences in early post resuscitation period. Biomarkers (NSE - neuron specific enolase, protein S100, GFAP - glial fibrillary acidic protein), imaging (computer tomography, magnetic resonance imaging) and functional studies (EEG - electro encephalography, SSEP - somatosensory evoked potentials) have all shown only limited prognostic value in predicting survival with good neurological outcome after cardiac arrest.

Mitochondrial damage is one of key mechanisms of postresuscitation dysfunction. Elevated values of mitochondrial damage-associated molecular patterns were already linked to worst survival after cardiac arrest and critical illness.

Mitochondrial damage often results in cell death and mitochondrial damage-associated molecular patterns are released into bloodstream. Mitochondrial damage-associated molecular patterns that can be detected in serum or plasma are: mitochondrial DNA, mitochondrial transcription factor A, N-formyl peptides, succinate, cardiolipin, cytochrome C...

With a more sensitive method of early neuroprognostication after cardiac arrest the limited medical resources could be used more effectively in patients with chance of good neurological recovery.

Aim of the study

The aim of this study is to research the role of mitochondrial damage-associated molecular patterns in patients after cardiac arrest.

1. Determine normal plasma values of mitochondrial damage-associated molecular patterns in healthy population.
2. Compare current prognostic procedures of post-resuscitation neurological damage with prognostic value of mitochondrial DNA and cytochrome C in plasma.

Expected results

Due to central role of mitochondria in hypoxic-ischemic tissue damage a greater mitochondrial damage (measured trough release of mitochondrial damage-associated molecular patterns) is expected to have direct correlation with extent of tissue damage (also neurological). Currently published data indicate that patients with higher plasma mitochondrial DNA levels after cardiac arrest have higher mortality. Correlation of mitochondrial damage-associated molecular patterns to extent of neurological damage in survivors of cardiac arrest was not researched yet.

Methods

1. Measurement of measure mitochondrial damage-associated molecular patterns in healthy population (mitochondrial DNA and cytochrome C).
2. Determination of releasing profile of mitochondrial DNA and cytochrome C in survivors of cardiac arrest and establishment of best sample collection time.
3. Calculation of predictive value for survival of cardiac arrest with good neurological outcome for mitochondrial DNA and cytochrome C.

Mitochondrial damage-associated molecular patterns will be measured in samples of plasma. Mitochondrial DNA will be measured using PCR method. Cytochrome C will be measured using ELISA.

Conditions

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Cardiac Arrest

Keywords

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biomarker

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Biomarker

Plasma mitochondrial DNA, plasma Cytochrome C

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* unconscious after cardiac arrest
* therapeutic hypothermia

Exclusion Criteria

* expected survival less than 24h
Minimum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Ljubljana

OTHER

Sponsor Role collaborator

University Medical Centre Ljubljana

OTHER

Sponsor Role lead

Responsible Party

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Peter Radsel

Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marko Noč, MD

Role: STUDY_CHAIR

UMC Ljubljana

Locations

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University Medical Centre Ljubljana, Ljubljana, Slovenia

Ljubljana, , Slovenia

Site Status

Countries

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Slovenia

References

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Greer DM, Rosenthal ES, Wu O. Neuroprognostication of hypoxic-ischaemic coma in the therapeutic hypothermia era. Nat Rev Neurol. 2014 Apr;10(4):190-203. doi: 10.1038/nrneurol.2014.36. Epub 2014 Mar 11.

Reference Type BACKGROUND
PMID: 24614515 (View on PubMed)

Girotra S, Chan PS, Bradley SM. Post-resuscitation care following out-of-hospital and in-hospital cardiac arrest. Heart. 2015 Dec;101(24):1943-9. doi: 10.1136/heartjnl-2015-307450. Epub 2015 Sep 18.

Reference Type BACKGROUND
PMID: 26385451 (View on PubMed)

Arnalich F, Codoceo R, Lopez-Collazo E, Montiel C. Circulating cell-free mitochondrial DNA: a better early prognostic marker in patients with out-of-hospital cardiac arrest. Resuscitation. 2012 Jul;83(7):e162-3. doi: 10.1016/j.resuscitation.2012.03.032. Epub 2012 Apr 7. No abstract available.

Reference Type BACKGROUND
PMID: 22490673 (View on PubMed)

Rodrigues Filho EM, Ikuta N, Simon D, Regner AP. Prognostic value of circulating DNA levels in critically ill and trauma patients. Rev Bras Ter Intensiva. 2014 Jul-Sep;26(3):305-12. doi: 10.5935/0103-507x.20140043.

Reference Type BACKGROUND
PMID: 25295826 (View on PubMed)

Nakahira K, Hisata S, Choi AM. The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases. Antioxid Redox Signal. 2015 Dec 10;23(17):1329-50. doi: 10.1089/ars.2015.6407. Epub 2015 Aug 17.

Reference Type BACKGROUND
PMID: 26067258 (View on PubMed)

Other Identifiers

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UKC-KOIIM-c-arrest

Identifier Type: -

Identifier Source: org_study_id