Immunoinflammatory Response in Post Cardiac Arrest Syndrome (PCAS)

NCT ID: NCT02664831

Last Updated: 2025-07-18

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

RECRUITING

Total Enrollment

400 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-01-31

Study Completion Date

2028-01-31

Brief Summary

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This is a prospective, observational study to investigate molecular mechanisms mediating the systemic inflammatory process, and changes to metabolism, and their impact on brain injury, survival, and functional outcomes after cardiac arrest. Investigators have shown that cardiac arrest induces changes in the numbers and properties of circulating immune cells, shifting the balance towards a pro-inflammatory phenotype and there is increased interest in the inflammatory pathways and the signaling mechanisms through which they are modulated. Participants will undergo blood sampling during 7 days following cardiac arrest, and analyses performed. Patient characteristics, clinical circumstances, and outcomes will be recorded and their associations with these inflammatory pathways characterized.

Detailed Description

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Preliminary evidence indicates that inter-individual variables such as immune cell activity and the production of pro-inflammatory factors may differentiate patients with the highest risk of poor neurological outcome, and may reveal novel therapeutic approaches based on promoting molecular pathways of inflammation-resolution and recovery to reduce the severity of hypoxic ischemic encephalopathy (HIE). Additionally, there are intrinsic, modifiable metabolic factors, such as the presence and metabolic activity of brown adipose tissue (BAT) that may modulate injury and recovery.

Comparative analysis showed that cardiac arrest survivors have more CD73+ lymphocytes compared to non-survivors. CD73 is the key enzyme in the generation of anti-inflammatory and immunosuppressive adenosine. We have also identified novel populations of neutrophils (CD14posCD16low and DEspR+) that had amplified response to inflammatory stimuli. The investigators hypothesize that individual variability in the expression and signaling profiles of white blood cells (lymphocytes, neutrophils, monocytes and macrophages) following resuscitation affects inflammation and is independently associated with neurological outcome. To test this hypothesis, investigators will determine levels of various immune cell populations at different time points in peripheral blood of patients. Characterization of blood circulating factors, clinical phenotypes, and neurological outcomes after cardiac arrest is a second aim of this project, with a focus on understanding the heterogeneity of cellular and humoral immune responses and how they relate to different clinical phenotypes of post-resuscitation syndrome.

PCAS metabolism:

IT is known that hyperglycemia is an independent risk factor for poor outcome after cardiac arrest, but it is not known if modification of hyperglycemia reduces this risk. Published studies have not demonstrated benefit with intensive insulin therapy. Our preliminary data suggest correlation between brown adipose tissue activity and good outcome. We have postulated that BAT may be activated by therapeutic hypothermia and may act as a glucose sink reducing the oxidative stress caused by hyperglycemia, and secondarily reducing injury to the brain, heart, and other organs.

In these studies we will also investigate other actionable targets for new therapies.

Conditions

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Cardiac Arrest Inflammation Obesity Hypoxic Ischemic Encephalopathy (HIE)

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

* Aged 18 years or older
* Admitted to the intensive care unit after cardiac arrest episode
* Unresponsive after resuscitation

Exclusion Criteria

* Moribund / actively dying at the time of evaluation
* Informed consent cannot be obtained within 24 hours of resuscitation
* Hemoglobin less than 7.0 g/dL, active high-volume bleeding, or requiring a transfusion
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

MaineHealth

OTHER

Sponsor Role lead

Responsible Party

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David B. Seder MD

Chair, Department of Critical Care Services

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sergey Ryzhov, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

MaineHealth Institute for Research

David B Seder, MD

Role: PRINCIPAL_INVESTIGATOR

MaineHealth

Locations

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Maine Medical Center

Portland, Maine, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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David B Seder, MD

Role: CONTACT

207-662-2179

Sergey Ryzhov, PhD

Role: CONTACT

Facility Contacts

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David B Seder, MD

Role: primary

207-662-2179

Sergey Ryzhov, MD, PhD

Role: backup

References

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deKay JT, Chepurko E, Chepurko V, Knudsen L, Lord C, Searight M, Tsibulnikov S, Robich MP, Sawyer DB, Gagnon DJ, May T, Riker R, Seder DB, Ryzhov S. Delayed CCL23 response is associated with poor outcomes after cardiac arrest. Cytokine. 2024 Apr;176:156536. doi: 10.1016/j.cyto.2024.156536. Epub 2024 Feb 6.

Reference Type BACKGROUND
PMID: 38325139 (View on PubMed)

Ryzhov S, May T, Dziodzio J, Emery IF, Lucas FL, Leclerc A, McCrum B, Lord C, Eldridge A, Robich MP, Ichinose F, Sawyer DB, Riker R, Seder DB. Number of Circulating CD 73-Expressing Lymphocytes Correlates With Survival After Cardiac Arrest. J Am Heart Assoc. 2019 Jul 2;8(13):e010874. doi: 10.1161/JAHA.118.010874. Epub 2019 Jun 25.

Reference Type BACKGROUND
PMID: 31237169 (View on PubMed)

Other Identifiers

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1P20GM139745-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DBS1

Identifier Type: -

Identifier Source: org_study_id

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