MultiStem for Trauma-Induced Multiple Organ Failure

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Charles Cox, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Healios K.K.

Must not be taking: Nephrotoxic, Immunosuppressive

Disqualifiers: Pregnancy, Non-survivable head injury, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for severely injured trauma patients who have just been hospitalized and survived initial resuscitation. The study aims to find better ways to help these critically injured patients recover.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using medications that affect the immune system or kidneys, you might need to stop or adjust them, as these are part of the exclusion criteria.

What data supports the effectiveness of the treatment MultiStem for trauma-induced multiple organ failure?

Research shows that similar treatments using multipotent adult progenitor cells (MAPCs) have been effective in reducing lung injury and improving survival in conditions like acute respiratory distress syndrome (ARDS) and sepsis in animal models. These findings suggest that MAPCs could potentially help in managing trauma-induced multiple organ failure by reducing inflammation and organ damage. ^{1 2 3 4 5}

Is MultiStem safe for humans?

Research shows that multipotent adult progenitor cells (MAPCs), also known as MultiStem, have been tested in humans for various conditions, including liver transplantation and acute respiratory distress syndrome, with no evidence of acute toxicity or serious adverse events. This suggests that MultiStem is generally safe for human use. ^{1 2 6 7 8}

How is the treatment MultiStem different from other treatments for trauma-induced multiple organ failure?

MultiStem is unique because it uses multipotent adult progenitor cells (MAPCs) that can help reduce inflammation and promote healing in multiple organs. Unlike traditional treatments, it is administered intravenously and works by modulating the body's immune response, potentially offering a novel approach to managing trauma-induced multiple organ failure. ^{1 2 3 9 10}

Research Team

Charles Cox, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

This trial is for adults over 18 who've had severe trauma, received blood products, and are stable enough to survive at least 24 hours post-injury. They must start treatment within a day of injury. Excluded are pregnant women, prisoners, those with certain kidney or immune conditions, large burns or non-survivable head injuries.

Inclusion Criteria

Your surgeon believes that your bleeding has been successfully stopped.

18 years of age or older

Received at least 3 units of any blood product in any hour before Shock Trauma Intensive Care Unit (STICU) arrival

Exclusion Criteria

Prisoners, defined as those who have been directly admitted from a correctional facility

Pregnant and lactating females

Hemodynamically unstable or requiring clinically meaningful escalation of vasopressor dose for blood pressure support during the 30 minute period prior to study product thawing/preparation

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either MultiStem or placebo shortly after hospitalization

Acute hospitalization period

Follow-up

Participants are monitored for mortality, hospital days, ventilator-free days, and ICU days

365 days

Treatment Details

Interventions

• MultiStem (Stem Cell Therapy)
• Placebo (Other)

Trial Overview The study tests MultiStem®, a stem cell therapy against a placebo in severely injured patients to see if it can prevent organ failure after trauma. It's randomized and double-blind meaning neither doctors nor patients know who gets the real treatment.

Participant Groups

Group I: MultiStem Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

MultiStem is already approved in Japan for the following indications:

Approved in Japan as MultiStem for:

• Acute Respiratory Distress Syndrome (ARDS)

Who Is Running the Clinical Trial?

Healios K.K.

Lead Sponsor

Trials

13

Recruited

1,500+

Athersys, Inc

Lead Sponsor

Trials

11

Recruited

1,200+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Pete Hegseth

United States Department of Defense

Chief Executive Officer

Bachelor's degree in Political Science from Princeton University, JD from Harvard Law School

Lisa Hershman

United States Department of Defense

Chief Medical Officer since 2021

MD from Uniformed Services University of the Health Sciences

Memorial Hermann Hospital

Collaborator

Trials

17

Recruited

56,300+

Findings from Research

In a phase 1/2 trial involving patients with moderate-to-severe acute respiratory distress syndrome (ARDS), intravenous multipotent adult progenitor cells were found to be safe and well tolerated, with no serious adverse reactions reported.

Patients receiving the cell therapy had a lower 28-day mortality rate (25%) compared to those receiving a placebo (45%), and they experienced significantly more days free from intensive care and ventilator use, suggesting potential clinical benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial. Bellingan, G., Jacono, F., Bannard-Smith, J., et al.[2023]

In a study involving 18 mini-pigs, it was found that after trauma-induced multiple organ dysfunction syndrome (MODS), the number of endothelial progenitor cells (EPCs) in peripheral blood sharply increased initially but then decreased significantly, indicating a potential early response to injury.

Conversely, the number of EPCs in bone marrow initially decreased slightly but then increased significantly during the progression of MODS, suggesting that changes in bone marrow EPCs are crucial for recovery from this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Changes in endothelial progenitor cells and their implications in multiple organ dysfunction syndrome caused by trauma in pigs]. Fu, WZ., Mao, AR., Luo, TH., et al.[2010]

Mesenchymal stromal cell (MSC) therapy has been shown to improve lung injury and survival in mice with sepsis, with specific changes in microRNA and gene expression identified as potential mechanisms of action.

The study found that MSC treatment downregulated miR-27a-5p and upregulated its target gene VAV3, suggesting that targeting miR-27a-5p could be a therapeutic strategy for managing acute lung injury and conditions like acute respiratory distress syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal/stem cells modulate response to experimental sepsis-induced lung injury via regulation of miR-27a-5p in recipient mice. Younes, N., Zhou, L., Amatullah, H., et al.[2020]

Human adipose tissue-derived mesenchymal stem cells (hATSCs) significantly reduce inflammatory cytokines and improve multi-organ injury in a rat model of endotoxemia, indicating their potential as a therapeutic option for severe inflammatory conditions.

The study involved 15 rats divided into three groups, showing that hATSCs not only decreased inflammation in the lungs but also prevented kidney cell death, highlighting their ability to modulate the immune response effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The therapeutic effect of human adult stem cells derived from adipose tissue in endotoxemic rat model. Shin, S., Kim, Y., Jeong, S., et al.[2021]

In a study of 20 patients with varying conditions, serum from those with systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) significantly increased the proliferation of endothelial progenitor cells (EPCs) compared to healthy controls, particularly in the SIRS group.

The research indicated that inflammation and oxidative stress levels were altered in EPCs due to serum exposure from patients with sepsis, suggesting that these conditions can impact the function and health of these important cells involved in blood vessel repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endothelial progenitor cells are influenced by serum of patients with systemic inflammatory response syndrome or multiple organ dysfunction. Pang, T., Chen, W., Lu, ZM., et al.[2017]

The first patient in the MiSOT-I study received mesenchymal stem cells (MAPCs) after a liver transplant, and the administration of these cells was technically feasible without any acute toxicity observed.

This study suggests that using MAPCs could potentially reduce the need for high levels of pharmacological immunosuppression in organ transplant recipients, which may help minimize side effects associated with traditional immunosuppressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Case Study: Multipotent Adult Progenitor Cells for Immunomodulation After Liver Transplantation. Soeder, Y., Loss, M., Johnson, CL., et al.[2021]

Human multipotent adult progenitor cells (MAPC) maintain high viability (95%) when infused through various needle sizes, although their viability is negatively affected by chlorhexidine, indicating the importance of infusion conditions for therapy.

Co-culturing MAPC with phenytoin and celecoxib does not impair their function and actually reduces inflammation, suggesting that these medications can be safely used alongside MAPC therapy for traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical parameters affecting multipotent adult progenitor cells in vitro. Jackson, ML., Ruppert, KA., Kota, DJ., et al.[2022]

In a phase 1 clinical trial involving 15 patients with severe sepsis, a single intravenous dose of allogeneic umbilical cord-derived mesenchymal stem cells (MSCs) was found to be safe and well tolerated, with no serious adverse events reported.

The study demonstrated that administering up to 3 × 10^6 cells/kg of MSCs did not result in any infusion-related complications or significant changes in inflammation markers, suggesting a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord-derived mesenchymal stem (stromal) cells for treatment of severe sepsis: aphase 1 clinical trial. He, X., Ai, S., Guo, W., et al.[2018]

Intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury significantly increases T regulatory cell populations in the spleen and plasma, enhancing the body's anti-inflammatory response.

MAPC therapy also leads to a higher M2/M1 macrophage ratio in the brain, indicating a shift towards neuroprotective M2 macrophages, which is associated with increased apoptosis of pro-inflammatory M1 macrophages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population. Walker, PA., Bedi, SS., Shah, SK., et al.[2021]

Bone marrow mesenchymal stem cells (BMSCs) effectively reduce inflammation and lung injury in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS), suggesting their potential as a treatment for ALI following multiple trauma.

BMSCs work by inhibiting the TLR2 and TLR4 signaling pathways, leading to decreased levels of pro-inflammatory factors (like TNFα, IL-6, and IL-1β) and increased levels of the anti-inflammatory factor IL-10, demonstrating their mechanism of action in reducing inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone Marrow Mesenchymal Stem Cells Suppress Acute Lung Injury Induced by Lipopolysaccharide Through Inhibiting the TLR2, 4/NF-κB Pathway in Rats with Multiple Trauma. Li, D., Pan, X., Zhao, J., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial. [2023]

2. China pubmed.ncbi.nlm.nih.gov

[Changes in endothelial progenitor cells and their implications in multiple organ dysfunction syndrome caused by trauma in pigs]. [2010]

3. England pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal/stem cells modulate response to experimental sepsis-induced lung injury via regulation of miR-27a-5p in recipient mice. [2020]

4. Australia pubmed.ncbi.nlm.nih.gov

The therapeutic effect of human adult stem cells derived from adipose tissue in endotoxemic rat model. [2021]

5. Italy pubmed.ncbi.nlm.nih.gov

Endothelial progenitor cells are influenced by serum of patients with systemic inflammatory response syndrome or multiple organ dysfunction. [2017]

6. England pubmed.ncbi.nlm.nih.gov

First-in-Human Case Study: Multipotent Adult Progenitor Cells for Immunomodulation After Liver Transplantation. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Clinical parameters affecting multipotent adult progenitor cells in vitro. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Umbilical cord-derived mesenchymal stem (stromal) cells for treatment of severe sepsis: aphase 1 clinical trial. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Bone Marrow Mesenchymal Stem Cells Suppress Acute Lung Injury Induced by Lipopolysaccharide Through Inhibiting the TLR2, 4/NF-κB Pathway in Rats with Multiple Trauma. [2022]