Immunoinflammatory Response in Post Cardiac Arrest Syndrome (PCAS)

Obesity Clinical Trial

— PCAS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02664831
• Other study ID #: DBS1
• Secondary ID: 1P20GM139745-01
• Status: Recruiting
• Start date: January 2016
• Est. completion date: March 20, 2026

Study information

• Verified date: March 2024
• Source: MaineHealth
• Contact: David B Seder, MD
• Phone: 207-662-2179
• Email: david.seder[@]mainehealth.org
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: March 20, 2026
• Est. primary completion date: January 20, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Inflammation
• Obesity
• Post-Cardiac Arrest Syndrome

Locations

Country	Name	City	State
United States	Maine Medical Center	Portland	Maine

Sponsors (2)

Lead Sponsor	Collaborator
MaineHealth	National Institute of General Medical Sciences (NIGMS)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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;176:15653 — View Citation

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 Ass — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlations between inflammatory markers and clinical outcomes	Correlations between inflammatory markers and clinical outcomes	14 days
Primary	Correlations between inflammatory markers and biomarkers of neurological and cardiac injury	Correlations between inflammatory markers and biomarkers of neurological and cardiac injury	7 days
Secondary	Characterization of post-resuscitation inflammatory mechanisms and their regulators	Characterization of post-resuscitation inflammatory mechanisms and their regulators	7 days