Clinical trial NCT06606119: The Role of Brain-Bone Marrow-Gut Interaction Following Major Trauma
Official title: The Role of Brain-Bone Marrow-Gut Interaction Following Major Trauma
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of General Medical Sciences (NIGMS)
First posted: 2024-09-20
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Acute Care Trauma ICU - Severe Blunt Trauma Orthopedic Injury Shock Orthopedic Clinic - Elective Hip Replacement

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.

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.

Eligibility criteria: Severe Trauma Cohort

Inclusion Criteria:

1. All adults (age ≥18).
2. Blunt trauma with an injury severity score \> 15 and a long bone or pelvic fracture requiring open reduction internal fixation or intramedullary fixation
3. 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

Exclusion Criteria:

1. Patients not expected to survive greater than 48 hours
2. Prisoners
3. Pregnancy
4. Previous bone marrow transplantation
5. Patients receiving chronic corticosteroids or immunosuppression therapies
6. Patients with End Stage Renal Disease
7. Patients with any pre-existing hematological disease
8. Surgery for repair of injury is greater than seven days after admission to the hospital for trauma
9. Burn injury greater than 20% TBSA

Elective Hip Cohort

Inclusion Criteria

1. All adults (age ≥55).
2. Patient undergoing elective hip repair for non-infectious reasons.
3. Ability to obtain Informed Consent prior to operation.

Exclusion Criteria

1. Patients not expected to survive greater than 48 hours
2. Prisoners
3. Pregnancy
4. Previous bone marrow transplantation
5. Patients receiving chronic corticosteroids or immunosuppression therapies
6. Patients with End Stage Renal Disease
7. Patients with any pre-existing hematological disease

Primary outcomes:
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.
timeFrame: 3 years
measure: Determine the connection between changes in the microbiome with sympathetic stress-induced changes establishing gut-brain communication following trauma.
timeFrame: 3 years
measure: Link changes in the microbiome with altered HSPC and erythroid progenitor cells fate establishing gut-bone marrow communication following trauma
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: UF Academic Research Building
state: Florida
city: Gainesville
country: United States
facility: UF Health at Shands Hospital
state: Florida
city: Gainesville
country: United States
facility: UF Laboratory of Inflammation Biology and Surgical Science and Shands Hospital at UF
state: Florida
Study officials:
affiliation: University of Florida
name: Alicia Mohr, MD
role: PRINCIPAL_INVESTIGATOR
References: