NCT02577731 · University of Florida
Hematopoietic Stem Cell Dysfunction in the Elderly After Severe Injury
What this study is about
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.
View original scientific description
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.
Interventions
OTHER
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.
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.
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.
Primary outcome measures
Analyze the genomics response of hematopoietic cells between the groups
Time frame: Baseline
Through negative isolation columns and flow sorting to isolate the hematopoietic stem cells (HSCs) from a sample for appropriate analysis. The sample will then be enriched using a lineage depletion column which will remove all mature hematopoietic cells. The HSCs will be phenotyped and sorted as CD34+ CD38- Thy1+ CD45RA-. HSCs will be lysed and the RNA genomic content will be isolated. The genomic content will then be processed onto a GeneChip® microarray to analyze the genomic expression.
Analyze the muscle dysfunction between the groups for oxidative stress
Time frame: Baseline
Analyze the muscle dysfunction between the groups for mitochondrial activity
Time frame: Baseline
Analyze the muscle dysfunction between the groups for apoptosis
Time frame: Baseline
Analyze the muscle dysfunction between the groups for autophagy
Time frame: Baseline
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- All adults (age ≥18 to 54)
- Blunt and/or penetrating trauma resulting in long bone or pelvic fractures requiring ORIF or closed reduction percutaneous pinning (CRPP).
- Blunt and/or penetrating trauma patient with 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
- Or injury severity score (ISS) greater than or equal to 15.
- All adults (age 55 and older) require:
- Blunt and/or penetrating trauma resulting in log bone or pelvic fractures requiring ORIF or CRPP
- 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
- Or Injury Severity Score (ISS) greater than or equal to 15.
- Ability to obtain Informed Consent prior to OR repair of injury.
Exclusion criteria
- Patients not expected to survive greater than 48 hours.
- Patients receiving chronic corticosteroids or immunosuppression therapies.
- Previous bone marrow transplantation.
- Patients with End Stage Renal Disease.
- Patients with any pre-existing hematological disease. Elective Hip Repair Population Inclusion criteria will be:
- All adults (age ≥18)
- Patient undergoing elective hip repair for non-infectious reasons.
- Ability to obtain Informed Consent prior to operation. Exclusion Criteria will be:
- Patients receiving chronic corticosteroids or immunosuppression therapies.
- History of receiving Chemotherapy or Radiation within the last 6 months
- Previous bone marrow transplantation 7\. Patients with End Stage Renal Disease 8. Patients with any pre-existing hematological disease
Where
- Gainesville, Florida
Collaborators
National Institute of General Medical Sciences (NIGMS)
Related conditions & keywords
Frequently asked questions
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Will I receive a placebo instead of treatment?
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Data: ClinicalTrials.gov · synced Jan 15, 2026 · Source of record for eligibility and locations