Prognostic Value of Plasma Mitochondrial DNA and Cytochrome C After Cardiac Arrest
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:
- Determine plasma concentrations of mitochondrial DNA and cytochrome C in healthy population.
- Determine release profile of mitochondrial DNA and cytochrome C to plasma after cardiac arrest.
- Determine plasma prognostic value of mitochondrial DNA and cytochrome C after cardiac arrest and compare it with established prognostic methods.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
- Determine normal plasma values of mitochondrial damage-associated molecular patterns in healthy population.
- 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
- Measurement of measure mitochondrial damage-associated molecular patterns in healthy population (mitochondrial DNA and cytochrome C).
- Determination of releasing profile of mitochondrial DNA and cytochrome C in survivors of cardiac arrest and establishment of best sample collection time.
- 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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Ljubljana, Slovenia, 1000
- University Medical Centre Ljubljana, Ljubljana, Slovenia
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- unconscious after cardiac arrest
- therapeutic hypothermia
Exclusion Criteria:
- expected survival less than 24h
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Correlation of plasma mitochondrial DNA and cytochrome C with survival with good neurological outcome (CPC 1 and 2) at hospital discharge
Time Frame: In hospital mortality, 30days
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Relationship between plasma mitochondrial DNA and cytochrome C with neurological damage after cardiac arrest
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In hospital mortality, 30days
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Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Marko Noč, MD, UMC Ljubljana
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UKC-KOIIM-c-arrest
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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