Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis

NCT05110937 | Recruiting

• 3 other identifiers: IRB202100559RM1GM139690R35GM140806
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

Adverse outcomes in surgical sepsis patients are secondary to dysregulated emergency myelopoiesis, and expansion of myeloid-derived suppressor cells. Here we propose to determine the underlying mechanisms behind the increased expansion of these leukocyte populations and the underlying mechanisms that drive inflammation and immune suppression.

Conditions

Sepsis; Trauma Injury

Outcome Measures

Primary Outcomes (1)

• The total number of neutrophils and early myeloid derived suppressor cells will be measured and will be used to determine the magnitude of myelopoiesis dysfunction.

  The total number of neutrophils and early Myeloid derived suppressor cells will be measured at sepsis onset and during hospitalization and at 3 and 6 months.

  6 months

Study Arms (3)

Sepsis

Blood collection: Blood will be collected from patient at day 4, day 7, day 14-21 and at 3 and 6 months.

Other: Blood sampling

Healthy Controls

Blood Collection. The healthy volunteer participants will donate a blood sample. These controls will allow the investigators to determine if the values obtained are accurate, reliable, and repeatable.

Other: Blood sampling

Trauma

Blood collection: Blood will be collected from patient at day 4, day 7, day 14-21 and at 3 and 6 months.

Other: Blood sampling

Interventions

Blood sampling OTHER

Blood sampling

Healthy Controls; Sepsis; Trauma

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients admitted to surgical and trauma intensive care units who screen positive for sepsis and are being treated by our standard-of-care sepsis protocol are candidates for the studies proposed in this proposal. For the purpose of these studies, sepsis will be defined using the new Sepsis-3 criteria. Patients admitted to the surgical and trauma intensive care units who have severe blunt trauma injury and have high risk of in-hospital sepsis.

You may qualify if:

• age ≥18 years
• meets criteria for sepsis/septic shock by Sepsis-3 consensus criteria.

You may not qualify if:

• have disease states that predispose to significant immune system dysfunction
• have comorbidity burden or goals of care that preclude recovery after sepsis. These criteria include:
• a. irreversible shock (death \<12 hours) b. uncontrollable surgical source of sepsis c. patients deemed to be futile care or have advanced directives limiting resuscitative efforts d. alternative diagnoses causing shock state (e.g., hemorrhage, myocardial infarction or pulmonary embolus) e. known HIV infection with CD4+ count \<200 cells/mm3 g. severe traumatic brain injury with unencumbered assessment of GCS equaling 3 on admission to the intensive care unit.
• known pregnancy
• enrollment \>96 hours after suspected sepsis onset
• pre-hospitalization bedridden performance status (WHO/Zubrod score ≥4)
• subsequent clinical adjudication diagnosis not consistent with sepsis/septic shock by Sepsis-3 criteria.
• Burn injury greater than 20% total body surface area (tBSA)
• Trauma Participant:
• All adults age ≥ 18 years
• Blunt trauma patient with a. Injury Severity Score (ISS) greater than or equal to 25 b. ISS \> 15 and one of the following: i. \> 4 units of PRBC or \>3 units of whole blood or \>1500 ml of autogenous blood product in the first 24 hours of admission ii. AIS (acute injury score) \> 2 spine iii. Shock on arrival (Systolic blood pressure (SBP) \< 90)
• c. ISS \> 15 and two of the following: i. Age \> 55 ii. AIS \> 2 chest iii. +ETOH (ethyl alcohol) on arrival iv. Any red blood cell transfusion in first 24 hours
• Patients not expected to survive greater than 48 hours.
• Prisoners.
• Pregnancy.

Sponsors & Collaborators

• National Institute of General Medical Sciences (NIGMS): collaborator
• University of Florida: lead

Study Sites (1)

UF Health at Shands hospital

Gainesville, Florida, 32610, United States

RECRUITING

MeSH Terms

Conditions

Sepsis; Accidental Injuries

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Lyle Moldawer, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Philip Efron, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Tyler Loftus, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Lanz, MSN

CONTACT

352-273-5497; jennifer.lanz@surgery.ufl.edu

Ruth Davis, BSN

CONTACT

352-273-5897; ruth.davis@surgery.ufl.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: November 8, 2021
• Study Start: January 4, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: December 26, 2025

Record last verified: 2025-12

Locations

US (1)