Hematopoietic Stem Cell Dysfunction in the Elderly After Severe Injury

NCT ID: NCT02577731

Last Updated: 2026-01-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2027-12-31

Brief Summary

Traumatic injury is a leading cause of morbidity and mortality in young adults, and remains a substantial economic and health care burden. Despite decades of promising preclinical and clinical investigations in trauma, investigators understanding of these entities is still incomplete, and few therapies have shown success. During severe trauma, bone marrow granulocyte stores are rapidly released into the peripheral circulation. This release subsequently induces the expansion and repopulation of empty or evacuated space by hematopoietic stem cells (HSCs). Although the patient experiences an early loss of bone marrow myeloid-derived cells, stem cell expansion is largely skewed towards the repopulation of the myeloid lineage/compartment. The hypothesis is that this 'emergency myelopoiesis' is critical for the survival of the severely traumatized and further, failure of the emergency myelopoietic response is associated with global immunosuppression and susceptibility to secondary infection. Also, identifying the release of myeloid derived suppressor cells (MDSCs) in the circulation of human severe trauma subjects. This process is driven by HSCs in the bone marrow of trauma subjects. Additionally, MDSCs may have a profound effect on the nutritional status of the host. The appearance of these MDSCs after trauma is associated with a loss of muscle tissue in these subjects. This muscle loss and possible increased catabolism have huge effects on long term outcomes for these subjects. It is the investigator's goal to understand the differences that occur in these in HSCs and muscle cells as opposed to non-injured and non-infected controls. This work will lead to a better understanding of the myelopoietic and catabolic response following trauma.

Detailed Description

This is a prospective study to understand how trauma injuries changes the hematopoeitic stem cells (HSCs) in the bone marrow and muscle cells after trauma injury in elderly subjects is different when compared to non-injured subjects.

There will be three groups for this study: 1) Elective hip surgery subjects, 2) Trauma subjects and 3) deidentified bone marrow of healthy controls.

Samples of bone marrow and a blood sample will be collected at the time of surgery. The deidentified bone marrow of healthy controls will come from a tissue bank.

The blood will be used to perform PB colony assays, ELISAs to test for the following parameters: EPO, G-CSF, Reticulocyte, iron levels and cytokines and inflammatory markers.

The bone marrow and blood samples will be processed and sorted to isolate hematopoeitic stem cells for genomic content to determine genomic expression, oxidative stress, mitochondrial activity, apoptosis, autophagy, analysis of circulating erythroid progenitor cells, reticulocytes, granulocyte-colony stimulating factor assays, erythropoietin and iron levels.

Clinical data and hemodynamic measurements will be collected daily while subjects are hospitalized and trauma surgery subjects will be followed to evaluate for malunion and subsequent additional surgical procedures for repair.

Conditions

Trauma Injury

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Severe Trauma

Bone marrow collection. Blood collection. Clinical data collection.

Group Type: OTHER

Bone marrow collection

Intervention Type: OTHER

Bone marrow will be collected from the patient at time of orthopedic repair in the operating room. A second sample may be collected if the patient is required to return to the operating room for further repair of orthopedic injury.

Blood collection

Intervention Type: OTHER

Blood sample collection will be collected from the patient at time of orthopedic repair in the operating room. A second sample may be collected if the patient is required to return to the operating room for further repair of orthopedic injury.

Clinical data collection

Intervention Type: OTHER

Clinical data collection will encompass demographic information, past and present medical records, laboratory, microbiology, and all other test results, x-ray, CT, MRI, US and all other imaging test results, records about any medication received during admission, records of physical exam during admission, records of all vital signs and hemodynamic monitoring during admission, records of any procedure or intervention during admission, records of any procedure or intervention during hospital admission, condition at the discharge and discharge facility.

Elective Hip Repair

Bone marrow collection. Blood collection. Clinical data collection.

Group Type: OTHER

Bone marrow collection

Intervention Type: OTHER

Bone marrow will be collected from the patient at time of orthopedic repair in the operating room. A second sample may be collected if the patient is required to return to the operating room for further repair of orthopedic injury.

Blood collection

Intervention Type: OTHER

Blood sample collection will be collected from the patient at time of orthopedic repair in the operating room. A second sample may be collected if the patient is required to return to the operating room for further repair of orthopedic injury.

Clinical data collection

Intervention Type: OTHER

Clinical data collection will encompass demographic information, past and present medical records, laboratory, microbiology, and all other test results, x-ray, CT, MRI, US and all other imaging test results, records about any medication received during admission, records of physical exam during admission, records of all vital signs and hemodynamic monitoring during admission, records of any procedure or intervention during admission, records of any procedure or intervention during hospital admission, condition at the discharge and discharge facility.

Healthy Young Bone Marrow Control

Deidentified freshly isolated bone marrow samples from healthy young control subjects will be purchased for a tissue bank.

Group Type: OTHER

Bone marrow collection

Intervention Type: OTHER

Bone marrow will be collected from the patient at time of orthopedic repair in the operating room. A second sample may be collected if the patient is required to return to the operating room for further repair of orthopedic injury.

Interventions

Bone marrow collection

Bone marrow will be collected from the patient at time of orthopedic repair in the operating room. A second sample may be collected if the patient is required to return to the operating room for further repair of orthopedic injury.

Intervention Type: OTHER

Blood collection

Blood sample collection will be collected from the patient at time of orthopedic repair in the operating room. A second sample may be collected if the patient is required to return to the operating room for further repair of orthopedic injury.

Intervention Type: OTHER

Clinical data collection

Clinical data collection will encompass demographic information, past and present medical records, laboratory, microbiology, and all other test results, x-ray, CT, MRI, US and all other imaging test results, records about any medication received during admission, records of physical exam during admission, records of all vital signs and hemodynamic monitoring during admission, records of any procedure or intervention during admission, records of any procedure or intervention during hospital admission, condition at the discharge and discharge facility.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. All adults (age ≥18 to 54)

2. Blunt and/or penetrating trauma resulting in long bone or pelvic fractures requiring ORIF or closed reduction percutaneous pinning (CRPP).

3. Blunt and/or penetrating trauma patient with either:

1. hemorrhagic shock defined by: i. systolic BP (SBP) ≤ 90 mmHg or ii. mean arterial pressure≤ 65 mmHg or iii. base deficit (BD) ≥ 5 meq or iv. lactate ≥ 2

2. Or injury severity score (ISS) greater than or equal to 15.

4. All adults (age 55 and older) require:

1. Blunt and/or penetrating trauma resulting in log bone or pelvic fractures requiring ORIF or CRPP

2. Either hemorrhagic shock defined by: i. Systolic BP (SBP) ≤ 90 mmHg or ii. Mean arterial pressure ≤ 65 mmHg or iii. Base deficit (BD) ≥5 meq or iv. Lactate ≥ 2

3. Or Injury Severity Score (ISS) greater than or equal to 15.

5. Ability to obtain Informed Consent prior to OR repair of injury.

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.

Elective Hip Repair Population

1. Pregnancy.

2. Prisoners.

3. Patients receiving chronic corticosteroids or immunosuppression therapies.

4. History of receiving Chemotherapy or Radiation within the last 6 months

5. Previous bone marrow transplantation

7. Patients with End Stage Renal Disease 8. Patients with any pre-existing hematological disease

• Minimum Eligible Age: 18 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

University of Florida

Locations

UF Health Shands Hospital at the University of Florida

Gainesville, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jennifer D Lanz, MSN

Role: CONTACT

jennifer.lanz@surgery.ufl.edu

352-273-5497

Ruth J Davis, ASN

Role: CONTACT

ruth.davis@surgery.ufl.edu

352-273-8759

Facility Contacts

Jennifer Lanz, MSN

Role: primary

jennifer.lanz@surgery.ufl.edu

352-273-5497

Ruth Davis, ASN

Role: backup

ruth.davis@surgery.ufl.edu

352-273-8759

References

Munley JA, Willis ML, Gillies GS, Kannan KB, Polcz VE, Balch JA, Barrios EL, Wallet SM, Bible LE, Efron PA, Maile R, Mohr AM. Exosomal microRNA following severe trauma: Role in bone marrow dysfunction. J Trauma Acute Care Surg. 2024 Apr 1;96(4):548-556. doi: 10.1097/TA.0000000000004225. Epub 2023 Dec 28.

Reference Type: DERIVED

PMID: 38151766 (View on PubMed)

Munley JA, Kelly LS, Gillies GS, Kannan KB, Pons EE, Bible LE, Efron PA, Mohr AM. EFFECTS OF TRAUMA PLASMA-DERIVED EXOSOMES ON HEMATOPOIETIC PROGENITOR CELLS. Shock. 2023 Apr 1;59(4):591-598. doi: 10.1097/SHK.0000000000002094. Epub 2023 Feb 16.

Reference Type: DERIVED

PMID: 36772985 (View on PubMed)

Other Identifiers

1R01GM113945-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB 106-2013

Identifier Type: OTHER

Identifier Source: secondary_id

5R01GM105893

Identifier Type: NIH

Identifier Source: secondary_id

View Link

OCR30562

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201601386-N

Identifier Type: -

Identifier Source: org_study_id