Pathological Myeloid Activation After Sepsis and Trauma

NCT ID: NCT05616130

Last Updated: 2024-12-24

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 255 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2028-09-30

Brief Summary

The goal of this observational study is to better understand what happens to circulating blood after a patient experiences severe trauma injury. The main questions it aims to answer are: Is severe human trauma associated with specific patterns of development in the hematopoietic stem cells of these patients? and Does the initial severe trauma injury create immunosuppression and increase risk of in-hospital sepsis? Participants in study will give blood samples and a waste sample of bone marrow at time of operative repair of traumatic orthopedic injuries, supply medical information and participate in surveys and assessments during recovery from their injury(ies). Researchers will compare severe trauma injury patients to elective hip repair patients to see if immunosuppression and specific development patterns occur in the trauma patient versus the otherwise healthy hip surgery patient.

Detailed Description

Severe trauma is linked with challenging clinical trajectories as well as dismal long-term outcomes following hospital discharge. In surgical intensive care units, an alarming percentage of trauma patients can develop chronic critical illness (CCI), a prolonged acute-care and chronic-care hospitalization with unresolved organ dysfunction. CCI frequently manifests as a persistent inflammation, immunosuppression and catabolism syndrome (PICS). Trauma survivors suffering from PICS have repeat infections, poor cognitive performance, physical dysfunction and self-reported poor quality of life. These conditions, at least in part, are due to an unresolving pathologic myelopoiesis and ensuing prevalence of distinct myeloid-derived suppressor cells (MDSCs). The investigator's laboratory has also discovered key distinctions in these MDSCs' accompanying pathologic myeloid activation, while concurrently, they produce inflammatory cytokines, reactive nitric oxide (NO), oxidation and peroxidation products that damage parenchymal cells and promote inflammation. In addition, there are hematopoietic stem and progenitor cells (HSPCs), from which these white blood cells are derived, in the bone marrow and blood that contribute to the development of these dysfunctional cells. The investigators hypothesize that epigenetic alterations and immunometabolism affect each other in relation to the development and suppressive activity of these MDSCs. The overarching goal is to build upon this foundation and expand our understanding of the patient immune response to trauma. The investigator's goal is to define the key aspects of MDSC and HSPC pathophysiology that engender and maintain pathologic myeloid activation and its pathology after trauma and subsequently modify these systems to mitigate or prevent chronic critical illness and persistent inflammation, immunosuppression and catabolism syndrome. Identification is done through direct data collection from participants and collection of blood over a 6 month period and a one-time bone marrow collection at time of trauma surgery repair and elective hip repair.

Conditions

Trauma Injury; Sepsis; Immunosuppression; Chronic Critical Illness

Study Design

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

Study Groups

Trauma

Data collection from medical records; bone marrow collection at time of surgical intervention; serial blood sampling; serial interviews to complete surveys and questionnaires which assess overall health, quality of life, daily living activities and mobility; serial physical function tests - hand grip strength measurement and short physical performance battery and telephone follow up call

Data Collection

Intervention Type: OTHER

Researcher will collect data from subject's medical records: information regarding your medical history, trauma injury, heart rate, blood pressure, temperature (vital signs), use of antibiotics (medications used to treat infection) and other medications, development of infection, and treatment results will be recorded and kept with your research records. Demographic information (such as name, address, phone number, gender, race, height and weight, age and birth date), medical record notes (including but not limited to history and physical exam notes, progress notes, consultation reports, laboratory test results, operative reports, information relating to acquired immunodeficiency virus (HIV) infection, radiologic (x-ray studies) results, and blood samples)

Bone marrow collection and blood collection

Intervention Type: PROCEDURE

At time of scheduled surgery, researcher will collect a 20ml (approximately 4 teaspoons) sample of bone marrow while you are in the operating room receiving surgery for your orthopedic (bone) injuries or elective hip repair. Blood collection will occur at time of surgery, day 14 on study or discharge from hospital and at 3 and 6 months. Up to 58 ml (about 4 tablespoons) sample of blood will be collected from an existing intravenous line or peripheral needle stick.

Serial interviews to complete surveys and questionnaires

Intervention Type: OTHER

Participants will be asked to complete questionnaires and surveys that assess your health, quality of life, daily living activities, and mobility. These activities occur at enrollment, day 14 in hospital or discharge, and at the 3, 6, and 12-month visits.

Telephone follow up call

Intervention Type: OTHER

The study team will contact you at 12 months to complete a telephone interview to learn about your health and well being.

Elective Hip Repair

Data collection from medical records; bone marrow collection at time of surgical intervention; serial blood sampling; serial interviews to complete surveys and questionnaires which assess overall health, quality of life, daily living activities and mobility; serial physical function tests - hand grip strength measurement and short physical performance battery and telephone follow up call

Data Collection

Intervention Type: OTHER

Researcher will collect data from subject's medical records: information regarding your medical history, trauma injury, heart rate, blood pressure, temperature (vital signs), use of antibiotics (medications used to treat infection) and other medications, development of infection, and treatment results will be recorded and kept with your research records. Demographic information (such as name, address, phone number, gender, race, height and weight, age and birth date), medical record notes (including but not limited to history and physical exam notes, progress notes, consultation reports, laboratory test results, operative reports, information relating to acquired immunodeficiency virus (HIV) infection, radiologic (x-ray studies) results, and blood samples)

Bone marrow collection and blood collection

Intervention Type: PROCEDURE

At time of scheduled surgery, researcher will collect a 20ml (approximately 4 teaspoons) sample of bone marrow while you are in the operating room receiving surgery for your orthopedic (bone) injuries or elective hip repair. Blood collection will occur at time of surgery, day 14 on study or discharge from hospital and at 3 and 6 months. Up to 58 ml (about 4 tablespoons) sample of blood will be collected from an existing intravenous line or peripheral needle stick.

Serial interviews to complete surveys and questionnaires

Intervention Type: OTHER

Participants will be asked to complete questionnaires and surveys that assess your health, quality of life, daily living activities, and mobility. These activities occur at enrollment, day 14 in hospital or discharge, and at the 3, 6, and 12-month visits.

Telephone follow up call

Intervention Type: OTHER

The study team will contact you at 12 months to complete a telephone interview to learn about your health and well being.

Interventions

Data Collection

Researcher will collect data from subject's medical records: information regarding your medical history, trauma injury, heart rate, blood pressure, temperature (vital signs), use of antibiotics (medications used to treat infection) and other medications, development of infection, and treatment results will be recorded and kept with your research records. Demographic information (such as name, address, phone number, gender, race, height and weight, age and birth date), medical record notes (including but not limited to history and physical exam notes, progress notes, consultation reports, laboratory test results, operative reports, information relating to acquired immunodeficiency virus (HIV) infection, radiologic (x-ray studies) results, and blood samples)

Intervention Type: OTHER

Bone marrow collection and blood collection

At time of scheduled surgery, researcher will collect a 20ml (approximately 4 teaspoons) sample of bone marrow while you are in the operating room receiving surgery for your orthopedic (bone) injuries or elective hip repair. Blood collection will occur at time of surgery, day 14 on study or discharge from hospital and at 3 and 6 months. Up to 58 ml (about 4 tablespoons) sample of blood will be collected from an existing intravenous line or peripheral needle stick.

Intervention Type: PROCEDURE

Serial interviews to complete surveys and questionnaires

Participants will be asked to complete questionnaires and surveys that assess your health, quality of life, daily living activities, and mobility. These activities occur at enrollment, day 14 in hospital or discharge, and at the 3, 6, and 12-month visits.

Intervention Type: OTHER

Telephone follow up call

The study team will contact you at 12 months to complete a telephone interview to learn about your health and well being.

Intervention Type: OTHER

Other Intervention Names

Telephone interview

Eligibility Criteria

Inclusion Criteria

1. All adults age ≥ 18 years

2. Blunt and/or penetrating trauma resulting in long bone or pelvic fractures requiring open reduction internal fixation or closed reduction percutaneous pinning

3. Blunt and/or penetrating 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 packed red blood cell 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 (SBP < 90)

OR

c. ISS > 15 and two of the following: i. Age > 55 ii. AIS > 2 chest iii. +ethyl alcohol on arrival iv. Any red blood cell transfusion in first 24 hours

1. All adults (age ≥18)

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. Patients receiving chronic corticosteroids or immunosuppression therapies.

5. Previous bone marrow transplantation.

6. Patients with End Stage Renal Disease.

7. Patients with any pre-existing hematological disease.

8. Patients deemed to be futile care or have advanced directives limiting resuscitative efforts.

9. Patients with severe congestive heart failure (NY Heart Association Class IV).

10. Known HIV infection with CD4+ (clusters of differentiation) count <200 cells/mm3

11. Chronic liver disease with MELD (Model for End-Stage Liver Disease) score ≥15

Elective Hip population

1. Pregnancy.

2. Prisoners.

3. Patients receiving chronic corticosteroids or immunosuppression therapies.

4. Pre-existing conditions such as pathological fractures, cancer, history of HIV, or history of connective tissue disease.

5. Previous bone marrow transplantation.

6. Patients with End Stage Renal Disease.

7. Patients with any pre-existing hematological disease.

8. Patients with known active/symptomatic COVID-19 (Coronavirus disease).

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

Sponsors

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

Philip Efron, MD

Role: PRINCIPAL_INVESTIGATOR

UF COM Department of Surgery

Locations

UF Health at Shands Hospital

Gainesville, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ruth Davis, BSN

Role: CONTACT

Phone: 352-273-8759

Email: ruth.davis@surgery.ufl.edu

Jennifer Lanz, MSN

Role: CONTACT

Phone: 352-273-5497

Email: jennifer.lanz@surgery.ufl.edu

Facility Contacts

Ruth Davis, BSN

Role: primary

Jennifer Lanz, MSN

Role: backup

Other Identifiers

RM1GM139690

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R35GM140806

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB202100572

Identifier Type: -

Identifier Source: org_study_id