Assessing Immune Dysfunction in Sepsis

University of Minnesota150 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

150

Conditions

Sepsis

Interventions

Observational OnlyOTHER

No intervention is included in this study

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

University of Minnesota

Minneapolis, Minnesota, United States

RECRUITING

Outcomes

Primary Outcomes

EliSpot - Day 1

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 1

EliSpot - Day 4

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 4

EliSpot - Day 7

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 7

EliSpot - Day 14

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 14

EliSpot - Day 21

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 21

EliSpot - Day 28

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 28

Ex Vivo TNF Production - Day 1

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 1

Ex Vivo TNF Production - Day 4

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 4

Central Contacts

Mrunmayi Tilak

CONTACT

612-624-9990 mtilak@umn.edu

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Ex Vivo TNF Production - Day 7

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Ex Vivo TNF Production - Day 14

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 14

Ex Vivo TNF Production - Day 21

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 21

Ex Vivo TNF Production - Day 28

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 28

Transcriptional Profiling - Day 1

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 1

Transcriptional Profiling - Day 4

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 4

Transcriptional Profiling - Day 7

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 7

Transcriptional Profiling - Day 14

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 14

Transcriptional Profiling - Day 21

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 21

Transcriptional Profiling - Day 28

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 28

CBC - Day 1

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 1

CBC - Day 4

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 4

CBC - Day 7

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 7

CBC - Day 14

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 14

CBC - Day 21

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 21

CBC - Day 28

Sample analysis to determine waxing and waning of Course of Sepsis parameters associated with clinical outcomes

Time frame: Day 28