Assessing Immune Dysfunction in Sepsis

Sepsis leads to sustained immune system dysfunction resulting in increased susceptibility to secondary infection while in the hospital or after discharge. Consequently, many of the ~2 million Americans that develop sepsis every year will end up back in the ICU, weeks and months later. The objective of this study is to define the cellular and molecular mechanisms driving the dysfunction and reprogramming of T cells and B cells that mediate cellular and humoral immunity using a combination of phenotypic, functional, genomic, and metabolomic assays.

Study Overview

• Status: Recruiting
• Conditions: Sepsis
• Intervention / Treatment: Other: Observational Only

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Kristine Kancans; Email: kanca008@umn.edukanca008@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Contact: Kristine Kancans; Email: kanca008@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with and without sepsis in the ICU, compared to healthy volunteers

Description

ICU With Sepsis Inclusion Criteria:

• Age ≥ 18
• Presumed diagnosis of sepsis, defined as "patients with life-threatening organ dysfunction caused by a dysregulated host response to infection"

• Patients in the ICU who meet 2 or more of the quick SOFA (qSOFA) definition along with organ dysfunction:

  1. Respiration rate ≥ 22 breaths/min and/or mechanically ventilated
  2. An alteration in mental status
  3. Systolic blood pressure of less than 100 mm Hg and/or receiving inotropes to maintain blood pressure AND/OR
  1. An acute change in SOFA score ≥2 points, consequent to the infection (can assume SOFA score = 0 in patients with no pre-existing organ dysfunction)

ICU Without Sepsis Inclusion Criteria:

• Age ≥ 18
• Patients requiring care at a M Health Fairview ICU due to high acuity of illness and no other evidence of sepsis

Healthy Volunteer Inclusion Criteria

• Age greater or equal to 18
• ASA status 1, 2 or 3
• May include patients who are receiving dialysis in an outpatient setting

Exclusion Criteria (all groups):

• Active cancer with chemotherapy and/or radiation treatment within the past 6 weeks
• Medication usage that includes immunosuppressive drugs, biologic agents, cytokines, growth factor and interleukins
• Steroid medication usage of > 300mg hydrocortisone per day (equivalent of > 20mg prednisone). Patients with chronic steroid use will be excluded, however patients who have had stress dose steroids administered following admission will be included.
• Patients with a history of, or who currently have evidence of autoimmune disease, including but not limited to: myasthenia gravis, Guillain Barré syndrome, systemic lupus erythematosus, multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's granulomatosis, HIV/AIDS, etc.
• Patients with active or a history of acute or chronic lymphocytic leukemia
• Known history of chronic hepatitis B (HBV) infection and not on treatment with HBV nucleoside analogues prior to the current hospitalization, or HBV DNA > 100 IU/mL
• Known history of infection with hepatitis C (HCV) and currently undergoing treatment for HCV infection or has detectable HCV RNA
• Participation in another investigational interventional drug study within the past 4 weeks
• Current pregnancy
• Current incarceration

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Volunteers	Other: Observational Only; No intervention is included in this study
ICU Patients with Sepsis	Other: Observational Only; No intervention is included in this study
ICU Patients without Sepsis	Other: Observational Only; No intervention is included in this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EliSpot - Day 1	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 1
EliSpot - Day 4	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 4
EliSpot - Day 7	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 7
EliSpot - Day 14	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 14
EliSpot - Day 21	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 21
EliSpot - Day 28	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 28
Ex Vivo TNF Production - Day 1	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 1
Ex Vivo TNF Production - Day 4	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 4
Ex Vivo TNF Production - Day 7	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 7
Ex Vivo TNF Production - Day 14	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 14
Ex Vivo TNF Production - Day 21	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 21
Ex Vivo TNF Production - Day 28	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 28
Flow Cytometry of Peripheral Blood Leukocytes - Day 1	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 1
Flow Cytometry of Peripheral Blood Leukocytes - Day 4	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 4
Flow Cytometry of Peripheral Blood Leukocytes - Day 7	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 7
Flow Cytometry of Peripheral Blood Leukocytes - Day 14	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 14
Flow Cytometry of Peripheral Blood Leukocytes - Day 21	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 21
Flow Cytometry of Peripheral Blood Leukocytes - Day 28	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 28
Quantification of Cytokines in Serum - Day 1	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 1
Quantification of Cytokines in Serum - Day 4	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 4
Quantification of Cytokines in Serum - Day 7	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 7
Quantification of Cytokines in Serum - Day 14	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 14
Quantification of Cytokines in Serum - Day 21	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 21
Quantification of Cytokines in Serum - Day 28	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 28
Quantification of Chemokines in Serum - Day 1	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 1
Quantification of Chemokines in Serum - Day 4	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 4
Quantification of Chemokines in Serum - Day 7	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 7
Quantification of Chemokines in Serum - Day 14	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 14
Quantification of Chemokines in Serum - Day 21	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 21
Quantification of Chemokines in Serum - Day 28	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 28
Transcriptional Profiling - Day 1	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 1
Transcriptional Profiling - Day 4	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 4
Transcriptional Profiling - Day 7	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 7
Transcriptional Profiling - Day 14	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 14
Transcriptional Profiling - Day 21	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 21
Transcriptional Profiling - Day 28	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 28
CBC - Day 1	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 1
CBC - Day 4	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 4
CBC - Day 7	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 7
CBC - Day 14	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 14
CBC - Day 21	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 21
CBC - Day 28	Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes	Day 28

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Thomas Griffith, PhD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: August 26, 2025
• First Submitted That Met QC Criteria: August 26, 2025
• First Posted (Actual): September 4, 2025

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis
• Other Study ID Numbers: URO-2025-34202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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