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

NCT ID: NCT06606119

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 275 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-01-24
• Study Completion Date: 2028-10-01

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.

Conditions

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Data and tissue collection

Intervention Type: OTHER

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

Elective Hip Replacement

Patients undergoing elective hip replacement surgery

Data and tissue collection

Intervention Type: OTHER

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

Interventions

Data and tissue collection

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

Intervention Type: OTHER

Eligibility Criteria

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

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

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alicia Mohr, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

UF Academic Research Building

Gainesville, Florida, United States

Site Status: RECRUITING

UF Health at Shands Hospital

Gainesville, Florida, United States

Site Status: RECRUITING

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

Gainesville, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ruth Davis, BSN

Role: CONTACT

ruth.davis@surgery.ufl.edu

352-273-8759

Jennifer Lanz, MSN

Role: CONTACT

jennifer.lanz@surgery.ufl.edu

352-273-5497

Facility Contacts

Kolenkode B Kannan, PhD

Role: primary

Kolenkode.Kannan@surgery.ufl.edu

352-273-8455

Alicia Mohr, MD

Role: backup

alicia.mohr@surgery.ufl.edu

352-273-5670

Ruth Davis, BSN

Role: primary

ruth.davis@surgery.ufl.edu

352-273-8759

Jennifer Lanz, MSN

Role: backup

352-273-5497

Other Identifiers

1R35GM152216-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB202400903

Identifier Type: -

Identifier Source: org_study_id