Immunoinflammatory Response in Post Cardiac Arrest Syndrome (PCAS) (PCAS)

July 15, 2025 updated by: David B. Seder MD, MaineHealth

Immunoinflammatory and Metabolic Responses in Post Cardiac Arrest Syndrome (PCAS)

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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

400

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

Study Contact Backup

Study Locations

  • United States
    • Maine
      • Portland, Maine, United States, 04102
        • Recruiting
        • Maine Medical Center
        • Contact:
        • Contact:
        • Sub-Investigator:
          • David J Gagnon, PharmD
        • Principal Investigator:
          • David B Seder, MD
        • Principal Investigator:
          • Sergey Ryzhov, MD, PhD
        • Sub-Investigator:
          • Teresa May, DO
        • Sub-Investigator:
          • Richard Riker, MD
        • Sub-Investigator:
          • Angela M Leclerc, PA-C
        • Sub-Investigator:
          • Brittany Lachance, DO
        • Sub-Investigator:
          • Patrick T Mailloux, DO
        • Sub-Investigator:
          • Matthew Lynes, PhD

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Cardiac arrest survivors with encephalopathy admitted to the intensive care unit and unresponsive after resuscitation

Description

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

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlations between inflammatory markers and clinical outcomes
Time Frame: 14 days
Correlations between inflammatory markers and clinical outcomes
14 days
Correlations between inflammatory markers and biomarkers of neurological and cardiac injury
Time Frame: 7 days
Correlations between inflammatory markers and biomarkers of neurological and cardiac injury
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterization of post-resuscitation inflammatory mechanisms and their regulators
Time Frame: 7 days
Characterization of post-resuscitation inflammatory mechanisms and their regulators
7 days
Brown Fat activity
Time Frame: 2 weeks
Correlations between 12,13 diHOME, blood glucose, and outcome
2 weeks

Collaborators and Investigators

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

Sponsor

MaineHealth

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
National Institute of General Medical Sciences (NIGMS)

Investigators

  • Principal Investigator: David B Seder, MD, MaineHealth
  • Principal Investigator: Sergey Ryzhov, MD, PhD, MaineHealth Institute for Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

January 1, 2016

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

January 22, 2016

First Submitted That Met QC Criteria

January 26, 2016

First Posted (Estimated)

January 27, 2016

Study Record Updates

Last Update Posted (Actual)

July 18, 2025

Last Update Submitted That Met QC Criteria

July 15, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DBS1
  • 1P20GM139745-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results reported in any publications, after deidentification.

IPD Sharing Time Frame

Beginning 9 months and ending 6 months following article publication

IPD Sharing Access Criteria

Investigators whose proposed use of the data has been approved by an independent review committee.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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