Trauma InjuryNCT06606119
The Role of Brain-Bone Marrow-Gut Interaction Following Major Trauma
An observational study of Trauma Injury and Trauma, run by University of Florida at 3 sites in United States.
Trial summary
Traumatic injury followed by critical illness provokes pathophysiologic changes in the bone marrow and the gut that contribute to persistent anemia and changes in the microbiome which significantly impact long-term recovery. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Trauma Injury, Trauma, Critical Illness
- What is being tested?
- Data and tissue collection
- How many people
- 275 participants
- Where
- 3 sitesUnited States
- Study dates
- 24 Jan 2025to 1 Oct 2028
- 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
- No healthy volunteers
- Adult, Older adult
Study population: Acute Care Trauma ICU - Severe Blunt Trauma Orthopedic Injury Shock Orthopedic Clinic - Elective Hip Replacement
Who may be able to join
- All adults (age ≥18).
- Blunt trauma with an injury severity score > 15 and a long bone or pelvic fracture requiring open reduction internal fixation or intramedullary fixation
- Blunt trauma patients with shock, defined by either a systolic BP (SBP) <90 mm Hg or base deficit (BD) ≥5 meq or lactate ≥ 2 mmol/L or active red blood cell or whole blood transfusion within 6h or arrival
- All adults (age ≥55).
- Patient undergoing elective hip repair for non-infectious reasons.
- Ability to obtain Informed Consent prior to operation.
Who cannot join
- Patients not expected to survive greater than 48 hours
- Prisoners
- Pregnancy
- Previous bone marrow transplantation
- Patients receiving chronic corticosteroids or immunosuppression therapies
- Patients with End Stage Renal Disease
Show all 17Show fewer
- Patients with any pre-existing hematological disease
- Surgery for repair of injury is greater than seven days after admission to the hospital for trauma
- Burn injury greater than 20% TBSA
- Elective Hip Cohort
- Patients not expected to survive greater than 48 hours
- Prisoners
- Pregnancy
- Previous bone marrow transplantation
- Patients receiving chronic corticosteroids or immunosuppression therapies
- Patients with End Stage Renal Disease
- Patients with any pre-existing hematological disease
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
UF Academic Research Building
Gainesville, Florida, 32610
Kolenkode B Kannan, PhD, 352-273-8455, Kolenkode.Kannan@surgery.ufl.edu
Alicia Mohr, MD, 352-273-5670, alicia.mohr@surgery.ufl.edu
- Recruiting
UF Health at Shands Hospital
Gainesville, Florida, 32610
Ruth Davis, BSN, 352-273-8759, ruth.davis@surgery.ufl.edu
Jennifer Lanz, MSN, 352-273-5497
- Recruiting
UF Laboratory of Inflammation Biology and Surgical Science and Shands Hospital at UF
Gainesville, Florida, 32610
Alicia L Mohr, MD
About this study
Traumatic injury followed by critical illness provokes pathophysiologic changes in the bone marrow and the gut that contribute to persistent anemia and changes in the microbiome which significantly impact long-term recovery. This project will define the interactions between the stress, chronic inflammation, bone marrow dysfunction, and an altered microbiome which will provide a strong foundation for future clinical interventions to help improve outcomes following severe trauma.
Read the detailed description
Trauma remains the leading cause of death among people younger than 46 years of age and is the leading cause of years of potential life lost among those younger than 65. With more lives saved, trauma morbidity has increased, which has consequently revealed a lack of understanding of the impact of trauma survivorship on the patients' quality of life and long-term recovery. Severe injury when followed by chronic critical illness leads to persistent anemia, and the use of blood transfusions is associated with a linear increase in infectious complications. These conditions are due to prolonged bone marrow dysfunction associated with an exaggerated catecholamine response, chronic stress, and systemic inflammation. Our laboratory has conducted human research to establish that there are unique bone marrow transcriptomic differences related to inflammation, the innate immune response, and known inhibitors of erythropoiesis following trauma. The laboratory has also discovered that chronic stress after trauma contributes to persistent anemia with impaired iron and erythropoietin function along with the prolonged loss of hematopoietic stem progenitor cells (HSPC) from the bone marrow. Chronic stress after trauma also induces an altered microbiome with decreased alpha and beta diversity and changes in microbial composition leading to a persistent 'pathobiome'. All of these factors influence outcomes. We hypothesize that there is a unifying interaction between stress, inflammation, and the microbiome and this has an overall role in the regulation of HSPC and erythroid progenitor cell fate and function following trauma and critical illness. Therefore, the overarching goal for this study is to build upon this foundation and expand our understanding of HSPC fate and function following trauma, including examining interventions aimed at reducing stress/inflammation and restoring the microbiome, thus, improving long-term outcomes.
- Conditions
- Trauma Injury, Trauma, Critical Illness, Microbiome, Chronic Anemia, Acute Blood Loss Anemia
- Being tested
- Data and tissue collection
- Keywords
- Hematopoietic Stem Progenitor Cells, Bone Marrow Failure, Anemia, Gut Microbiome, Inflammation, Dysregulated Stress Response
- Medical subject headings
- Accidental Injuries, Wounds and Injuries, Critical Illness, Bone Marrow Failure Disorders, Anemia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Data and tissue collectionOther
Collection of bone marrow, blood, feces, medical record data, and patient response surveys.
| Study group | Role | What they receive |
|---|---|---|
| Major Trauma Injury | Severe blunt trauma patients diagnosed with shock with a long bone or pelvic fracture requiring open reduction internal fixation or intramedullary fixation. Receives: Other: Data and tissue collection | |
| Elective Hip Replacement | Patients undergoing elective hip replacement surgery Receives: Other: Data and tissue collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Link the changes in HSPC and erythroid progenitor cell fate and function with sympathetic stress-induced changes establishing brain-bone marrow communication following trauma.
The impact of the severity and duration of catecholamine secretion on the cellular biology of HSPCs and erythroid progenitor cells requires further detailed evaluation. At each stage of proliferation and differentiation, there is a complex interaction of cytokines, transcription factors, post-translational modification of histones, and miRs. Single-cell RNA-seq technologies using a novel second generation multi-omics technology, CITE-seq, will be used for identification of isolated HSPCs and erythroid progenitor cells. Such single cell sequencing technology is ideal for cell populations with a great deal of heterogeneity and is well-suited for bone marrow analysis. Isolated cells can then be characterized by their transcriptomic and epigenetic changes. We will also evaluate EVM cargo (specific proteins/RNA/miR) from both plasma and bone marrow to determine links to chronic stress exposure.
Measured: 3 years
Determine the connection between changes in the microbiome with sympathetic stress-induced changes establishing gut-brain communication following trauma.
Focusing on the effects of autonomic nervous system on gut function and immune responses, in the setting of sympathetic activation, a serial evaluation of the gut microbiota and their metabolic products (ex. SCFAs: butyrate, propionate, and acetate) will be performed in trauma patients. Correlation of microbial diversity and alterations of the taxonomic composition will be correlated with plasma markers of inflammation and clinical outcomes. Longitudinal study of the trauma pathobiome will elucidate clinical course patterns (recovery and CCI) with microbial composition. The unique biology of the microbiome in different sexes and age groups will require additional subgroup analysis.
Measured: 3 years
Link changes in the microbiome with altered HSPC and erythroid progenitor cells fate establishing gut-bone marrow communication following trauma
We will examine how stress-induced changes following trauma create a pathobiome that modulates HPSC differentiation and maintains altered erythroid progenitor function. The microbiota play a role in both lineage differentiation and also control systemic iron homeostasis by inhibiting intestinal absorption and increasing cellular iron storage. Bone marrow macrophages have a key role in late-stage erythropoiesis by supplying local iron to erythroblasts for hemoglobin production. Isolation of bone marrow macrophages and erythroblasts involved in EBIs and determination of local iron content will define microbiome-induced changes in terminal erythropoiesis.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2024
- Study start24 Jan 2025
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Trauma InjuryStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 275 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Sponsor
- Investigators
- Alicia Mohr, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06606119
- Sponsor's protocol ID
- IRB202400903
- Other IDs
- 1R35GM152216-01
- Status last verified
- Feb 2026
- First submitted
- 18 Sep 2024
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Brain-Bone Marrow-Gut Interaction Following Major Trauma
- ClinicalTrials.gov ID
- NCT06606119
- Acronym / sponsor ID
- IRB202400903
- Conditions
- Trauma Injury, Trauma, Critical Illness, Microbiome, Chronic Anemia, Acute Blood Loss Anemia
- Keywords
- Hematopoietic Stem Progenitor Cells, Bone Marrow Failure, Anemia, Gut Microbiome, Inflammation, Dysregulated Stress Response
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 275 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS)
- Study start
- 24 Jan 2025 (actual)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 20 Sep 2024 (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.
Traumatic injury followed by critical illness provokes pathophysiologic changes in the bone marrow and the gut that contribute to persistent anemia and changes in the microbiome which significantly impact long-term recovery. This project will define the interactions between the stress, chronic inflammation, bone marrow dysfunction, and an altered microbiome which will provide a strong foundation for future clinical interventions to help improve outcomes following severe trauma.
Detailed description
Trauma remains the leading cause of death among people younger than 46 years of age and is the leading cause of years of potential life lost among those younger than 65. With more lives saved, trauma morbidity has increased, which has consequently revealed a lack of understanding of the impact of trauma survivorship on the patients' quality of life and long-term recovery. Severe injury when followed by chronic critical illness leads to persistent anemia, and the use of blood transfusions is associated with a linear increase in infectious complications. These conditions are due to prolonged bone marrow dysfunction associated with an exaggerated catecholamine response, chronic stress, and systemic inflammation. Our laboratory has conducted human research to establish that there are unique bone marrow transcriptomic differences related to inflammation, the innate immune response, and known inhibitors of erythropoiesis following trauma. The laboratory has also discovered that chronic stress after trauma contributes to persistent anemia with impaired iron and erythropoietin function along with the prolonged loss of hematopoietic stem progenitor cells (HSPC) from the bone marrow. Chronic stress after trauma also induces an altered microbiome with decreased alpha and beta diversity and changes in microbial composition leading to a persistent 'pathobiome'. All of these factors influence outcomes. We hypothesize that there is a unifying interaction between stress, inflammation, and the microbiome and this has an overall role in the regulation of HSPC and erythroid progenitor cell fate and function following trauma and critical illness. Therefore, the overarching goal for this study is to build upon this foundation and expand our understanding of HSPC fate and function following trauma, including examining interventions aimed at reducing stress/inflammation and restoring the microbiome, thus, improving long-term outcomes.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Major Trauma Injury | – | Other: Data and tissue collectionSevere blunt trauma patients diagnosed with shock with a long bone or pelvic fracture requiring open reduction internal fixation or intramedullary fixation. |
| Elective Hip Replacement | – | Other: Data and tissue collectionPatients undergoing elective hip replacement surgery |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Acute Care Trauma ICU - Severe Blunt Trauma Orthopedic Injury Shock Orthopedic Clinic - Elective Hip Replacement
Key inclusion criteria (6 listed)
- All adults (age ≥18).
- Blunt trauma with an injury severity score > 15 and a long bone or pelvic fracture requiring open reduction internal fixation or intramedullary fixation
- Blunt trauma patients with shock, defined by either a systolic BP (SBP) <90 mm Hg or base deficit (BD) ≥5 meq or lactate ≥ 2 mmol/L or active red blood cell or whole blood transfusion within 6h or arrival
- All adults (age ≥55).
- Patient undergoing elective hip repair for non-infectious reasons.
Key exclusion criteria (17 listed)
- Patients not expected to survive greater than 48 hours
- Prisoners
- Pregnancy
- Previous bone marrow transplantation
- Patients receiving chronic corticosteroids or immunosuppression therapies
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 |
|---|---|---|
| Data and tissue collectionCollection of bone marrow, blood, feces, medical record data, and patient response surveys. | Other | Elective Hip Replacement, Major Trauma Injury |
Primary outcome
Link the changes in HSPC and erythroid progenitor cell fate and function with sympathetic stress-induced changes establishing brain-bone marrow communication following trauma.
Time frame: 3 years
The impact of the severity and duration of catecholamine secretion on the cellular biology of HSPCs and erythroid progenitor cells requires further detailed evaluation. At each stage of proliferation and differentiation, there is a complex interaction of cytokines, transcription factors, post-translational modification of histones, and miRs. Single-cell RNA-seq technologies using a novel second generation multi-omics technology, CITE-seq, will be used for identification of isolated HSPCs and erythroid progenitor cells. Such single cell sequencing technology is ideal for cell populations with a great deal of heterogeneity and is well-suited for bone marrow analysis. Isolated cells can then be characterized by their transcriptomic and epigenetic changes. We will also evaluate EVM cargo (specific proteins/RNA/miR) from both plasma and bone marrow to determine links to chronic stress exposure.
Determine the connection between changes in the microbiome with sympathetic stress-induced changes establishing gut-brain communication following trauma.
Time frame: 3 years
Focusing on the effects of autonomic nervous system on gut function and immune responses, in the setting of sympathetic activation, a serial evaluation of the gut microbiota and their metabolic products (ex. SCFAs: butyrate, propionate, and acetate) will be performed in trauma patients. Correlation of microbial diversity and alterations of the taxonomic composition will be correlated with plasma markers of inflammation and clinical outcomes. Longitudinal study of the trauma pathobiome will elucidate clinical course patterns (recovery and CCI) with microbial composition. The unique biology of the microbiome in different sexes and age groups will require additional subgroup analysis.
Link changes in the microbiome with altered HSPC and erythroid progenitor cells fate establishing gut-bone marrow communication following trauma
Time frame: 3 years
We will examine how stress-induced changes following trauma create a pathobiome that modulates HPSC differentiation and maintains altered erythroid progenitor function. The microbiota play a role in both lineage differentiation and also control systemic iron homeostasis by inhibiting intestinal absorption and increasing cellular iron storage. Bone marrow macrophages have a key role in late-stage erythropoiesis by supplying local iron to erythroblasts for hemoglobin production. Isolation of bone marrow macrophages and erythroblasts involved in EBIs and determination of local iron content will define microbiome-induced changes in terminal erythropoiesis.
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 6 Feb 2026.
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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.
Alicia Mohr, MD principal investigator
University of Florida
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Trauma Injury and Trauma, run by University of Florida at 3 sites 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 17 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 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 Ruth Davis, BSN (352-273-8759, ruth.davis@surgery.ufl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Link the changes in HSPC and erythroid progenitor cell fate and function with sympathetic stress-induced changes establishing brain-bone marrow communication following trauma. (time frame: 3 years). The study lists 3 primary outcomes in all. 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 6 Feb 2026.