The Role of Brain-Bone Marrow-Gut Interaction Following Major Trauma

NCT06606119 | Recruiting

• 2 other identifiers: IRB2024009031R35GM152216-01
• Study Type: observational
• Target: 275
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Acute Blood Loss Anemia; Trauma Injury; Trauma; Critical Illness; Microbiome; Chronic Anemia

Keywords

Hematopoietic Stem Progenitor Cells; Bone Marrow Failure; Anemia; Gut Microbiome; Inflammation; Dysregulated Stress Response

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  3 years

Study Arms (2)

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.

Other: Data and tissue collection

Elective Hip Replacement

Patients undergoing elective hip replacement surgery

Other: Data and tissue collection

Interventions

Data and tissue collection OTHER

Collection of bone marrow, blood, feces, medical record data, and patient response surveys.

Elective Hip Replacement; Major Trauma Injury

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Acute Care Trauma ICU - Severe Blunt Trauma Orthopedic Injury Shock Orthopedic Clinic - Elective Hip Replacement

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• All adults (age ≥55).
• Patient undergoing elective hip repair for non-infectious reasons.
• Ability to obtain Informed Consent prior to operation.
• Patients not expected to survive greater than 48 hours
• Prisoners

Sponsors & Collaborators

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

Study Sites (3)

UF Academic Research Building

Gainesville, Florida, 32610, United States

RECRUITING

UF Health at Shands Hospital

Gainesville, Florida, 32610, United States

RECRUITING

UF Laboratory of Inflammation Biology and Surgical Science and Shands Hospital at UF

Gainesville, Florida, 32610, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Bone Marrow, Blood, Feces

MeSH Terms

Conditions

Accidental Injuries; Wounds and Injuries; Critical Illness; Bone Marrow Failure Disorders; Anemia; Inflammation

Interventions

Tissue Banks

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Biological Specimen Banks; Health Facilities; Health Care Facilities Workforce and Services

Study Officials

• Alicia Mohr, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruth Davis, BSN

CONTACT

352-273-8759; ruth.davis@surgery.ufl.edu

Jennifer Lanz, MSN

CONTACT

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

Study Design

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

Study Record Dates

• First Submitted: September 18, 2024
• First Posted: September 20, 2024
• Study Start: January 24, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

US (3)