MultiStem for Trauma-Induced Multiple Organ Failure

Recruiting at 1 trial location

Overseen By Jeanette Podbielski, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Healios K.K.

Must not be taking: Nephrotoxic, Immunosuppressive

Disqualifiers: Pregnancy, Non-survivable head injury, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Acute hospitalization period

156 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the new treatment, MultiStem, can aid patients with severe injuries at risk of multiple organ failure. MultiStem, a type of stem cell therapy, might reduce damage and enhance recovery after trauma. Participants will receive either MultiStem or a placebo (a harmless substance with no active treatment) to compare outcomes. Ideal candidates include those who have received significant blood transfusions and have survived initial emergency care. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that MultiStem, a type of stem cell therapy, has undergone testing in earlier studies to ensure safety. These studies found that patients generally tolerated the treatment well. For instance, one study on patients with multiple organ issues found that the treatment did not cause serious side effects such as heart problems or organ failure.

Another study examined MultiStem for various health issues and also found no major safety concerns. Patients did not experience severe unexpected medical problems during treatment. This suggests that MultiStem is safe for humans, although further research is ongoing to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for trauma-induced multiple organ failure?

Unlike the standard of care for trauma-induced multiple organ failure, which typically involves supportive measures like fluids, medications to support blood pressure, and mechanical ventilation, MultiStem offers a novel approach. It is derived from stem cells and aims to modulate the immune response, potentially reducing inflammation and promoting tissue repair. Researchers are excited about MultiStem because it could target the underlying causes of organ failure rather than just managing symptoms, offering a more comprehensive solution. Additionally, its potential to accelerate recovery and improve outcomes in critical care settings sets it apart from current treatments.

What evidence suggests that MultiStem might be an effective treatment for trauma-induced multiple organ failure?

Research shows that treatments like MultiStem, which use stem cells, hold promise for aiding serious injuries. In this trial, participants may receive MultiStem, which studies have found to lower inflammation and aid recovery from conditions like multiple organ failure after severe injuries. Early evidence suggests that these cells might enhance the body's ability to heal itself after injury. These findings support MultiStem's potential in treating multiple organ failure caused by trauma. ^{4 6 7 8 9}

Who Is on the Research Team?

Charles Cox, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

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.

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

Survived to initial ICU 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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• MultiStem
• Placebo

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.

How Is the Trial Designed?

Group I: MultiStem Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

MultiStem is already approved in United States, Japan for the following indications:

Approved in United States as MultiStem for:

• Acute Respiratory Distress Syndrome (ARDS)
• Trauma-induced multiple organ failure/Systemic Inflammatory Response Syndrome

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+

Memorial Hermann Hospital

Collaborator

Trials

17

Recruited

56,300+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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