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Hematopoietic Stem Cell Dysfunction in the Elderly After Severe Injury

ConditionTrauma Injury
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Florida

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

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.

Disqualifiers

Patients not expected to survive greater than 48 hours.

Prisoners.

Pregnancy.

Patients receiving chronic corticosteroids or immunosuppression therapies.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Bone marrow collection

    Other intervention

    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

    Other intervention

    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

    Other intervention

    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.

Treatment groups

400 Participants
are divided into 3 treatment groups
Group A: Severe TraumaOther 3 interventions
Group B: Elective Hip RepairOther 3 interventions
Group C: Healthy Young Bone Marrow ControlOther 1 intervention

Trial outcomes

Primary outcomes

1

Analyze the genomics response of hematopoietic cells between the groups

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.

Time frame
Baseline
2

Analyze the muscle dysfunction between the groups for oxidative stress

Time frame
Baseline
3

Analyze the muscle dysfunction between the groups for mitochondrial activity

Time frame
Baseline
4

Analyze the muscle dysfunction between the groups for apoptosis

Time frame
Baseline

Secondary outcomes

1

The pathophysiology of injury-associated persistent anemia through PB colony assays of blood.

Time frame
Baseline
2

The pathophysiology of injury-associated persistent anemia through ELISA test of blood.

Time frame
Baseline

Other outcomes

1

Analyze the genomics response of hematopoietic cells between the groups at additional follow-up surgery

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.

Time frame
Approximately 8 months
2

Analyze the muscle dysfunction between the groups at additional follow-up surgery for oxidative stress

Time frame
Approximately 8 months
3

Analyze the muscle dysfunction between the groups at additional follow-up surgery for mitochondrial activity

Time frame
Approximately 8 months
4

Analyze the muscle dysfunction between the groups at additional follow-up surgery for apoptosis

Time frame
Approximately 8 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Florida

Lead sponsor

National Institute of General Medical Sciences (NIGMS)

Collaborator

Source ClinicalTrials.gov
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