Stem Cell Response After Traumatic Injury in the Elderly

Overseen By Kalia Sadasivan, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must not be taking: Corticosteroids, Immunosuppressants, Chemotherapy

Disqualifiers: Pregnancy, Renal disease, Hematological disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how stem cells in the bone marrow react after severe injuries. Researchers seek to determine how these cells aid in recovery and infection resistance. They focus on the impact of this process on muscle loss and overall health. The trial collects blood and bone marrow samples from individuals who have experienced severe trauma or are undergoing elective hip repair. Those with significant injuries involving broken bones who can consent before surgery might be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance recovery processes for future patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on chronic corticosteroids or immunosuppression therapies.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that collecting bone marrow is generally safe. In past studies, this procedure did not present major safety issues. For instance, a study on individuals with serious brain injuries found that using bone marrow cells did not cause unsafe side effects.

Other research suggests that stem cells from bone marrow could help treat injuries without causing harm. In this trial, researchers will collect bone marrow and blood samples, and existing studies indicate that these procedures are usually well-tolerated. It is advisable to discuss any concerns with a doctor before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how stem cells respond to trauma in the elderly, which could lead to breakthroughs in regenerative medicine. Unlike traditional treatments that focus on managing symptoms of traumatic injuries, this study investigates the body's natural healing processes at a cellular level. By collecting and analyzing blood and bone marrow samples, researchers hope to uncover new insights into how the elderly can heal more effectively. This could pave the way for innovative therapies that enhance recovery after severe injuries, potentially improving outcomes and quality of life for older patients.

What evidence suggests that this trial's treatments could be effective for traumatic injury in the elderly?

This trial will compare stem cell responses in different scenarios. Research has shown that after a severe injury, the body increases the production of special cells that make blood cells. This process, called emergency myelopoiesis, helps the body fight infections and heal. Without this response, the risk of infections and other complications rises. Studies suggest that certain cells released during this time can affect muscle health, leading to muscle loss and slowing recovery. Understanding these changes is crucial for improving recovery in trauma patients. Participants in the "Severe Trauma" arm will undergo bone marrow and blood collection, along with clinical data collection, to study these responses. The "Elective Hip Repair" arm will also involve bone marrow and blood collection, providing a comparison to the trauma group. Additionally, deidentified bone marrow samples from healthy young controls will be used for further comparison. ^{6 7 8 9 10}

Who Is on the Research Team?

Philip Efron, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for adults aged 55 and older with severe trauma from blunt or penetrating injuries, showing signs of hemorrhagic shock or having a high injury severity score. It also includes younger adults (18-54) with similar injuries requiring surgery. Excluded are those not expected to survive 48 hours, prisoners, pregnant women, patients with end-stage renal disease, hematological diseases, prior bone marrow transplants, or recent chemotherapy/radiation.

Inclusion Criteria

Ability to obtain Informed Consent prior to operation

Severe Trauma Population:

I have had a serious injury with a severity score of 15 or more.

Exclusion Criteria

I have not had chemotherapy or radiation in the last 6 months.

I have had a bone marrow transplant in the past.

I have end-stage kidney disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sample Collection and Initial Analysis

Bone marrow and blood samples are collected at the time of surgery for genomic and biochemical analysis

Baseline

1 visit (in-person)

Follow-up

Participants are monitored for genomic response and clinical outcomes, including malunion and additional surgical procedures

8 months

Follow-up surgery and clinical data collection

What Are the Treatments Tested in This Trial?

Interventions

• Blood collection
• Bone marrow collection
• Clinical data collection

Trial Overview The study investigates how severe injury affects stem cells in the elderly by collecting blood and bone marrow samples and clinical data. Researchers aim to understand 'emergency myelopoiesis'—the body's response to replenish immune cells after trauma—and its link to muscle loss and infection risk post-injury.

How Is the Trial Designed?

Group I: Severe Trauma Experimental Treatment 3 Interventions

Bone marrow collection. Blood collection. Clinical data collection.

Group II: Healthy Young Bone Marrow Control Experimental Treatment 1 Intervention

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

Group III: Elective Hip Repair Experimental Treatment 3 Interventions

Bone marrow collection. Blood collection. Clinical data collection.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Published Research Related to This Trial

Plerixafor, when used as a rescue treatment after chemotherapy and G-CSF mobilization, successfully allowed 69% of patients to achieve the target dose of CD34+ cells needed for stem cell collection on the first attempt.

Pre-apheresis factors, specifically the CD34+ cell count and platelet count, were significant predictors of successful stem cell collection, indicating that higher counts can reduce the need for additional apheresis procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Day -1 CD34+ Cells and Platelet Count Predict the Number of Apheresis in Poor-Mobilizer Patients Rescued by Plerixafor. Valentini, CG., Pellegrino, C., Putzulu, R., et al.[2023]

In a prospective randomized trial involving 97 patients with multiple myeloma and non-Hodgkin lymphoma, tbo-filgrastim was found to be not inferior to filgrastim in terms of stem cell mobilization efficacy, with a mean collection of 11.6 CD34+ cells/kg compared to 10.0 CD34+ cells/kg for filgrastim.

Both tbo-filgrastim and filgrastim showed similar safety profiles, indicating that tbo-filgrastim can be a safe and effective alternative to filgrastim for stem cell mobilization in patients undergoing autologous hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Prospective Randomized, Open-Label, Noninferiority Study of Tbo-Filgrastim (Granix) versus Filgrastim (Neupogen) in Combination with Plerixafor for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma and Non-Hodgkin Lymphoma. Bhamidipati, PK., Fiala, MA., Grossman, BJ., et al.[2021]

Plerixafor effectively mobilizes hematopoietic stem cells by blocking the CXCR4 receptor, leading to a significant increase in CD34+ cells in the peripheral blood, peaking about 10 hours after administration.

A predictive model developed from data of 45 pediatric patients shows a strong correlation between peripheral blood CD34+ counts and the volume of CD34+ cells collected during apheresis, allowing for better planning and assurance of successful stem cell collection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and validation of a predictive model to guide the use of plerixafor in pediatric population. Sebastien, B., Cheverton, P., Magnin, C., et al.[2022]

A retrospective study of adverse drug reactions from 1991 to 2018 found that filgrastim biosimilars, such as Grasin® and Zarzio®, reported higher rates of specific side effects compared to the originator Neupogen®, indicating potential differences in safety profiles.

The study revealed that some biosimilars, like Zarzio® and Tevagrastim®, had significant reports of drug ineffectiveness, suggesting that their efficacy may not match that of the original filgrastim, highlighting the need for further large-scale studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data. Rastogi, S., Shukla, S., Sharma, AK., et al.[2020]

In a study involving 15 patients with multiple myeloma and non-Hodgkin's lymphoma, the combination of G-CSF and the CXCR4 antagonist AMD3100 significantly increased the number of primitive blood progenitor cells (PBPC), enhancing their potential for bone marrow reconstitution.

Patients receiving PBPC mobilized with G-CSF and AMD3100 experienced faster recovery of leukocytes and platelets after transplantation, with 91% achieving complete hematologic reconstitution within 35 days, indicating improved efficacy of this mobilization strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study. Fruehauf, S., Veldwijk, MR., Seeger, T., et al.[2021]

The study found that both ior®LeukoCIM and Neupogen® had similar safety profiles, with mild to severe swelling of the hock-joint observed in rats, but all adverse effects were fully reversible.

Both products effectively increased white blood cell and neutrophil levels to a comparable extent, indicating similar pharmacodynamic and pharmacokinetic properties, supporting their classification as biosimilars.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Biosimilarity of ior®LeukoCIM Compared to Neupogen® Based on Toxicity, Pharmacodynamic, and Pharmacokinetic Studies in the Sprague-Dawley Rat. Licollari, A., Riddle, K., Taylor, SR., et al.[2018]

The biosimilar filgrastim-sndz (Zarxio) offers significant cost savings compared to reference filgrastim and pegfilgrastim for preventing chemotherapy-induced neutropenia, with savings ranging from $65 to $3,666 depending on the administration scenario and duration of treatment.

Filgrastim-sndz consistently demonstrated lower costs across various administration methods, making it a cost-effective option for patients undergoing chemotherapy, while maintaining the same efficacy as its reference counterparts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-efficiency analyses for the US of biosimilar filgrastim-sndz, reference filgrastim, pegfilgrastim, and pegfilgrastim with on-body injector in the prophylaxis of chemotherapy-induced (febrile) neutropenia. McBride, A., Campbell, K., Bikkina, M., et al.[2022]

Filgrastim significantly reduces the incidence of febrile neutropenia and severe neutropenia in patients undergoing chemotherapy, with relative risks of 0.63 and 0.50, respectively, based on a systematic review of 25 studies involving 1194 articles.

The most common adverse effect reported with filgrastim treatment is bone pain, which has a relative risk of 2.61, indicating it is a notable side effect to consider when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. Dale, DC., Crawford, J., Klippel, Z., et al.[2022]

In a clinical trial involving 37 allogeneic PBSC donors, the addition of plerixafor (P) significantly improved the mobilization of CD34+ stem cells, with median counts increasing from 15/µl after G-CSF alone to 44/µl after G-CSF plus P (p < 0.001).

Plerixafor treatment led to a median yield of 3.74 × 10^6 CD34+/kg recipient body weight on Day 2, compared to only 1.31 × 10^6 CD34+/kg on Day 1, with 57% of donors reaching the target cell count, and no severe adverse events reported, indicating its safety and efficacy for donors with poor mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage treatment with plerixafor in poor mobilizing allogeneic stem cell donors: results of a prospective phase II-trial. Hölig, K., Schmidt, H., Hütter, G., et al.[2022]

A study involving normal volunteers showed that combining rhIL-3 with rhG-CSF for progenitor cell mobilization is safe and well-tolerated, with adverse effects similar to those of the individual treatments.

The sequential administration of rhIL-3 followed by rhG-CSF significantly increased the number of circulating CD34+ cells, which are important for stem cell collection, making it an effective protocol for enhancing stem cell mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human interleukin-3 (rhIL-3) enhances the mobilization of peripheral blood progenitor cells by recombinant human granulocyte colony-stimulating factor (rhG-CSF) in normal volunteers. Huhn, RD., Yurkow, EJ., Tushinski, R., et al.[2017]

Citations

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Four-factor prothrombin complex concentrate is associated ... Our study demonstrates that the use of 4-PCC as an adjunct to FFP is associated with improved survival and reduction in transfusion requirements.

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Autologous bone marrow mononuclear cell administration ... Intrathecal administration of bone marrow mononuclear cells is safe and effective in improving motor function and quality of life in patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11938091/

An overview of stem cells and cell products involved in trauma ... This review provides a comprehensive overview of the therapeutic potential of stem cells and cell products for traumatic injuries.

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Treatment of Severe Adult Traumatic Brain Injury Using ... This study should determine if bone marrow harvest, BMMNC separation, and reinfusion is safe in adults with acute, severe TBI. Official Title.

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Clinical Review Memo - BALFAXAR Safety outcomes were as expected following surgical ... controlled clinical trial to assess the efficacy, safety and tolerance of Kcentra.