Cardiac ArrestPCASNCT02664831
Immunoinflammatory Response in Post Cardiac Arrest Syndrome (PCAS)
An observational study of Cardiac Arrest and Inflammation, run by MaineHealth at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cardiac Arrest, Inflammation, Obesity
- How many people
- 400 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to Jan 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Cardiac arrest survivors with encephalopathy admitted to the intensive care unit and unresponsive after resuscitation
Who may be able to join
- Aged 18 years or older
- Admitted to the intensive care unit after cardiac arrest episode
- Unresponsive after resuscitation
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sergey Ryzhov, PhD contact
United States1 site, 1 recruiting
- Recruiting
Maine Medical Center
Portland, Maine, 04102
David B Seder, MD, 207-662-2179, david.seder@mainehealth.org
Sergey Ryzhov, MD, PhD, Sergey.ryzhov@mainehealth.org
About this study
Official title: 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.
Read the 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.
- Keywords
- cardiac arrest, inflammation, immune, neuregulin, lymphocyte, neutrophil, brown adipose, HIE
- Medical subject headings
- Heart Arrest, Inflammation, Obesity, Hypoxia-Ischemia, Brain, Fibromatosis, Gingival, 2
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlations between inflammatory markers and clinical outcomes
Correlations between inflammatory markers and clinical outcomes
Measured: 14 days
Correlations between inflammatory markers and biomarkers of neurological and cardiac injury
Correlations between inflammatory markers and biomarkers of neurological and cardiac injury
Measured: 7 days
Secondary outcomes (2)
Characterization of post-resuscitation inflammatory mechanisms and their regulators
Characterization of post-resuscitation inflammatory mechanisms and their regulators
Measured: 7 days
Brown Fat activity
Correlations between 12,13 diHOME, blood glucose, and outcome
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2016 (estimated)
- Study startJan 2016
- Primary completionJan 2027 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiac ArrestStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- MaineHealth
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, David B. Seder MD, MaineHealth
- Investigators
- Sergey Ryzhov, MD, PhD, Principal investigator, MaineHealth Institute for ResearchDavid B Seder, MD, Principal investigator, MaineHealth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02664831
- Sponsor's protocol ID
- DBS1
- Other IDs
- 1P20GM139745-01
- Acronym
- PCAS
- Status last verified
- Jul 2025
- First submitted
- 22 Jan 2016
- Last updated
- 18 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in any publications, after deidentification.
Publications
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.
PubMed 38325139Ryzhov 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.
PubMed 31237169
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunoinflammatory and Metabolic Responses in Post Cardiac Arrest Syndrome (PCAS)
- ClinicalTrials.gov ID
- NCT02664831
- Acronym / sponsor ID
- PCAS / DBS1
- Keywords
- cardiac arrest, inflammation, immune, neuregulin, lymphocyte, neutrophil, brown adipose, HIE
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- MaineHealthUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2016 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 27 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Cardiac arrest survivors with encephalopathy admitted to the intensive care unit and unresponsive after resuscitation
Key inclusion criteria (3 listed)
- Aged 18 years or older
- Admitted to the intensive care unit after cardiac arrest episode
- Unresponsive after resuscitation
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlations between inflammatory markers and clinical outcomes
Time frame: 14 days
Correlations between inflammatory markers and clinical outcomes
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
2 secondary outcomes
Characterization of post-resuscitation inflammatory mechanisms and their regulators
Time frame: 7 days
Brown Fat activity
Time frame: 2 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2025.
- Results publication: PubMed 38325139deKay 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.
- Results publication: PubMed 31237169Ryzhov 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.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in any publications, after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sergey Ryzhov, PhD contact
Sergey Ryzhov, MD, PhD principal investigator
MaineHealth Institute for Research
David B Seder, MD principal investigator
MaineHealth
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiac Arrest and Inflammation, run by MaineHealth at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David B Seder, MD (207-662-2179, david.seder@mainehealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlations between inflammatory markers and clinical outcomes (time frame: 14 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02664831, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2025.