SepsisNCT05110937
Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis
An observational study of Sepsis and Trauma Injury, run by University of Florida at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Sepsis, Trauma Injury
- What is being tested?
- Blood sampling
- How many people
- 450 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jan 2022to 1 Apr 2029
- 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 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- age ≥18 years
- meets criteria for sepsis/septic shock by Sepsis-3 consensus criteria.
- 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)
- OR
- 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
Who cannot join
- 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:
- 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)
Show all 18Show fewer
- 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:
- Patients not expected to survive greater than 48 hours.
- Prisoners.
- Pregnancy.
- Previous bone marrow transplantation.
- Patients with End Stage Renal Disease.
- Patients with any pre-existing hematological disease.
- Patients deemed to be futile care or have advanced directives limiting resuscitative efforts.
- Known HIV infection with CD4+ count <200 cells/mm3
- Burn injury greater than 20% tBSA
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UF Health at Shands hospital
Gainesville, Florida, 32610
Jennifer Lanz, MSN, 352-273-5497, jennifer.lanz@surgery.ufl.edu
Ruth Davis, BSN, 325-273-5897, ruth.davis@surgery.ufl.edu
About this study
Official title: Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis Pathobiology Subtitle: Pathological Myeloid Activation After Sepsis and Trauma
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.
Read the detailed description
Our overarching hypothesis is that the consequences of surgical sepsis (death and poor quality of life) are the result of an unresolving host leukocyte dyscrasia, similar to other chronic conditions such as cancer and autoimmune disease. Specifically, the preferential expansion and self-perpetuation of myeloid-derived suppressor cells (MDSCs), propagated in part through epigenetic changes in both bone marrow (BM) progenitors and MDSCs, drives non-acute infectious and noninfectious complications after sepsis.
This Program will investigate in human surgical sepsis the underlying mechanisms that drive 'dysfunctional myelopoiesis', expansion of MDSC populations, suppressed T-cell quantities/function, and the development of patient's immunosuppressive/inflammatory endotypes. We will primarily focus on how MDSC expansion evolves over time in an observational study that follows surgical sepsis patients who do or do not rapidly recover. There are three specific aims: Aim 1. To test the hypothesis that perpetuation of host MDSCs after acute surgical sepsis drives poor long-term clinical outcomes in surgical sepsis, including but not limited to increased secondary infections. Aim 2. To test the hypothesis that failure to recover from surgical sepsis is driven by modifiable epigenetic alterations in circulating MDSCs that induce and prolong immunosuppressive endotypes. Aim 3. To identify the distinct immunosuppressive mechanisms of MDSCs from surgical sepsis patients over time, including immunometabolism, check-point inhibition, reactive oxygen and nitrogen production, and substrate availability. Using the established clinical infrastructure of the Sepsis and Critical Illness Research Center (SCIRC), a team science approach will be employed with collaborating PI's coming from multiple clinical and basic science disciplines. Aim 4. To test the hypothesis that in response to an initial inflammatory stimulus (severe blunt trauma) associated with a high risk of in-hospital sepsis, bone marrow (BM) hematopoietic stem cells (HSCs) promote immunosuppressive myelopoiesis at the expense of lymphopoiesis. With subsequent sepsis development, MDSCs induce their continued expansion through exocrine and paracrine signaling to HSCs. HSCs and MDSCs derived from severe blunt trauma patients will be analyzed for epigenetic and functional changes that initiate sepsis and continue the expansion of immunosuppressive MDSCs.
- Conditions
- Sepsis, Trauma Injury
- Being tested
- Blood sampling
- Medical subject headings
- Sepsis, Accidental Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplingOther
Blood sampling
| Study group | Role | What they receive |
|---|---|---|
| Sepsis | Blood collection: Blood will be collected from patient at day 4, day 7, day 14-21 and at 3 and 6 months. Receives: 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. Receives: 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. Receives: Other: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2021
- Study start4 Jan 2022
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Sponsor
- Investigators
- Lyle Moldawer, PhD, Principal investigator, University of FloridaPhilip Efron, MD, Principal investigator, University of FloridaTyler Loftus, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05110937
- Sponsor's protocol ID
- IRB202100559
- Other IDs
- RM1GM139690, R35GM140806
- Status last verified
- Dec 2025
- First submitted
- 14 Oct 2021
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis Pathobiology Subtitle: Pathological Myeloid Activation After Sepsis and Trauma
- ClinicalTrials.gov ID
- NCT05110937
- Acronym / sponsor ID
- IRB202100559
- Conditions
- Sepsis, Trauma Injury
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- 4 Jan 2022 (actual)
- Primary completion
- 1 Jul 2028 (estimated)
- Study completion
- 1 Apr 2029 (estimated)
- First posted
- 8 Nov 2021 (actual)
- 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.
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.
Detailed description
Our overarching hypothesis is that the consequences of surgical sepsis (death and poor quality of life) are the result of an unresolving host leukocyte dyscrasia, similar to other chronic conditions such as cancer and autoimmune disease. Specifically, the preferential expansion and self-perpetuation of myeloid-derived suppressor cells (MDSCs), propagated in part through epigenetic changes in both bone marrow (BM) progenitors and MDSCs, drives non-acute infectious and noninfectious complications after sepsis.
This Program will investigate in human surgical sepsis the underlying mechanisms that drive 'dysfunctional myelopoiesis', expansion of MDSC populations, suppressed T-cell quantities/function, and the development of patient's immunosuppressive/inflammatory endotypes. We will primarily focus on how MDSC expansion evolves over time in an observational study that follows surgical sepsis patients who do or do not rapidly recover. There are three specific aims: Aim 1. To test the hypothesis that perpetuation of host MDSCs after acute surgical sepsis drives poor long-term clinical outcomes in surgical sepsis, including but not limited to increased secondary infections. Aim 2. To test the hypothesis that failure to recover from surgical sepsis is driven by modifiable epigenetic alterations in circulating MDSCs that induce and prolong immunosuppressive endotypes. Aim 3. To identify the distinct immunosuppressive mechanisms of MDSCs from surgical sepsis patients over time, including immunometabolism, check-point inhibition, reactive oxygen and nitrogen production, and substrate availability. Using the established clinical infrastructure of the Sepsis and Critical Illness Research Center (SCIRC), a team science approach will be employed with collaborating PI's coming from multiple clinical and basic science disciplines. Aim 4. To test the hypothesis that in response to an initial inflammatory stimulus (severe blunt trauma) associated with a high risk of in-hospital sepsis, bone marrow (BM) hematopoietic stem cells (HSCs) promote immunosuppressive myelopoiesis at the expense of lymphopoiesis. With subsequent sepsis development, MDSCs induce their continued expansion through exocrine and paracrine signaling to HSCs. HSCs and MDSCs derived from severe blunt trauma patients will be analyzed for epigenetic and functional changes that initiate sepsis and continue the expansion of immunosuppressive MDSCs.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sepsis | – | Other: Blood samplingBlood collection: Blood will be collected from patient at day 4, day 7, day 14-21 and at 3 and 6 months. |
| Healthy Controls | – | Other: Blood samplingBlood 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. |
| Trauma | – | Other: Blood samplingBlood collection: Blood will be collected from patient at day 4, day 7, day 14-21 and at 3 and 6 months. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- age ≥18 years
- meets criteria for sepsis/septic shock by Sepsis-3 consensus criteria.
- 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)
- OR
Key exclusion criteria (18 listed)
- 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:
- known pregnancy
- enrollment >96 hours after suspected sepsis onset
- pre-hospitalization bedridden performance status (WHO/Zubrod score ≥4)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood samplingBlood sampling | Other | Healthy Controls, Sepsis, Trauma |
Primary outcome
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.
Time frame: 6 months
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.
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 19 Aug 2026.
- Individual participant dataSharing planned: Undecided
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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.
Lyle Moldawer, PhD principal investigator
University of Florida
Philip Efron, MD principal investigator
University of Florida
Tyler Loftus, MD principal investigator
University of Florida
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 Sepsis and Trauma Injury, run by University of Florida 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 6 inclusion and 18 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 19 Aug 2026. 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 Jennifer Lanz, MSN (352-273-5497, jennifer.lanz@surgery.ufl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Aug 2026.