Mesenchymal Stem Cells for Chronic Pancreatitis

(STEMCAP-1 Trial)

Overseen By Leah Benn

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Medical University of South Carolina

Must be taking: Opioids

Disqualifiers: Acute pancreatitis, Severe organ failure, HbA1c >10%, others

Compensation: Varies

Number of Visits: 4

Duration: 6 months

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This protocol aims to test whether an infusion of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs) can reduce pain associated with chronic pancreatitis (CP) and explore potential mechanisms of MSC action.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it requires that participants have been on a stable dose of opioids for the past 30 days, suggesting that you may need to continue your current opioid regimen.

What data supports the effectiveness of the treatment Mesenchymal Stem Cells for Chronic Pancreatitis?

Research shows that mesenchymal stem cells (MSCs) can reduce inflammation and tissue damage in animal models of pancreatitis. In particular, studies found that MSCs from bone marrow and fat tissue helped reduce inflammation and preserve pancreas structure in rats and mice with pancreatitis, suggesting potential benefits for treating this condition in humans. ^{1 2 3 4 5}

Is mesenchymal stem cell therapy safe for humans?

Mesenchymal stem cell therapy is generally considered safe in humans, with transient fever being the most common treatment-related side effect reported. ^{1 2 6 7 8}

How is the treatment with Mesenchymal Stem Cells different from other treatments for chronic pancreatitis?

Mesenchymal Stem Cells (MSCs) are unique because they have the potential to reduce inflammation and aid in tissue regeneration, which is not a feature of standard treatments for chronic pancreatitis. Unlike other therapies, MSCs can modulate the immune response and help prevent further pancreatic damage, offering a novel approach to managing the condition. ^{1 2 4 8 9}

Research Team

Hongjun N Wang, PhD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for individuals with chronic pancreatitis who experience ongoing pain. Participants should be adults who meet specific health criteria and have not responded well to standard pain treatments.

Inclusion Criteria

I have had chronic pancreatitis pain for over 6 months.

My opioid medication dose has been the same for the last 30 days.

Baseline Izbicki pain score > 30

Exclusion Criteria

Acute pancreatitis per 2012 revised Atlanta criteria within the last 30 days.

Score >7 on the Opioid Risk Tool

HbA1c >10%

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive an infusion of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs) or placebo

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

3 visits (in-person)

Treatment Details

Interventions

• Mesenchymal Stem Cells

Trial Overview The study is testing the safety and effectiveness of mesenchymal stem cells (MSCs) derived from bone marrow in reducing chronic pancreatitis pain, compared to a placebo.

Participant Groups

Group I: Experimental Cohort Experimental Treatment 1 Intervention

MSC

Group II: Validation Cohort Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Mesenchymal stromal cells (MSCs) show promise in treating pancreatitis, particularly in reducing inflammation in acute cases and fibrosis in chronic cases, based on a review of 18 studies.

However, due to significant variability in the types, sources, and dosages of MSCs used across studies, there is currently no consensus on the best type of MSCs for treatment, and no clinical trials have been conducted to further investigate their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal Stromal Cell Therapy for Pancreatitis: A Systematic Review. Ahmed, SM., Morsi, M., Ghoneim, NI., et al.[2022]

Human bone marrow-derived clonal mesenchymal stem cells (hcMSCs) showed significant potential in reducing inflammation and tissue damage in rat models of both mild and severe acute pancreatitis (AP), indicating their therapeutic efficacy.

Infusion of hcMSCs led to a decrease in inflammatory mediators and an increase in regulatory T cells (Foxp3+), suggesting a mechanism of action that involves modulating the immune response to promote healing in pancreatic tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats. Jung, KH., Song, SU., Yi, T., et al.[2022]

Adipose-derived mesenchymal stem cells (ASCs) significantly reduced pancreatic damage and fibrosis in a chronic pancreatitis mouse model, indicating their potential efficacy in treating this condition.

The study demonstrated that ASCs not only migrated to the pancreas and differentiated into acinar-like cells but also suppressed inflammation and tissue damage, suggesting a dual mechanism of action for their therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis via Differentiation into Acinar-like Cells in Mice. Sun, Z., Gou, W., Kim, DS., et al.[2023]

Mesenchymal stem cells (MSCs) derived from human pancreas exhibit a high potential for ex vivo expansion, capable of doubling in population every 30 hours and maintaining their characteristics over 30 passages, indicating their robustness for research and therapeutic applications.

These pancreatic MSCs can differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic, demonstrating their versatility and potential for use in tissue engineering and regenerative medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Identification and isolation of mesenchymal stem cells from human fetal pancreas]. Hu, Y., Wang, QY., Ma, L., et al.[2006]

In a study of 60 patients with severe acute pancreatitis, those receiving mesenchymal stem cell therapy alongside standard treatment showed significant improvements in homeostasis, immune response, and microcirculation compared to those receiving only standard treatment.

The therapy was particularly effective in patients with the T774T mutation of the eNOS gene, suggesting that genetic factors may influence the efficacy of mesenchymal stem cell treatment in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cell therapy for destructive pancreatitis]. Gasanova, SY.[2022]

A review of 62 randomized clinical trials involving 3546 participants found that mesenchymal stem cell (MSC) therapy is generally safe, with no serious adverse events like death or infection reported.

While MSC therapy was associated with some mild adverse effects such as transient fever and fatigue, it also showed a trend towards reducing the incidence of arrhythmia, suggesting a favorable safety profile compared to placebo treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of MSC therapy over the past 15 years: a meta-analysis. Wang, Y., Yi, H., Song, Y.[2021]

A meta-analysis of 152 randomized clinical trials involving 9228 individuals treated with mesenchymal stromal cells (MSCs) found that fever is the only adverse event closely associated with MSC therapy, with a significant odds ratio of 1.61.

The analysis also indicated that MSC therapy may lower the incidence of tachycardia and fatigue, although these findings were not statistically significant, suggesting a generally favorable safety profile for MSC treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient Fever: the Sole Treatment-Related Adverse Event associated with Mesenchymal Stromal Cells and Solid Clues from the Real World. Wang, Y., Mou, Q., Yi, H., et al.[2023]

Mesenchymal stem cells (MSCs) have shown promise in regenerative medicine due to their ability to secrete bioactive molecules that exert anti-inflammatory effects, making them a potential treatment for various gastrointestinal diseases, including acute and chronic pancreatitis.

Current research indicates that MSC therapy could effectively suppress inflammation in pancreatitis, although the specific mechanisms by which MSCs exert their therapeutic effects are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cell therapy for acute and chronic pancreatitis. Kawakubo, K., Ohnishi, S., Kuwatani, M., et al.[2021]

Stem cell therapy shows promise for treating acute and chronic pancreatitis by potentially aiding in regeneration and preventing further pancreatic and organ injury, which could reduce complications associated with these conditions.

Research indicates that stem cells possess immunomodulatory properties, and various studies in animal models support their clinical potential in managing pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell therapy: a potential for the perils of pancreatitis. Chela, H., Romana, BS., Madabattula, M., et al.[2021]

References

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

Mesenchymal Stromal Cell Therapy for Pancreatitis: A Systematic Review. [2022]

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

Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats. [2022]

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

Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis via Differentiation into Acinar-like Cells in Mice. [2023]

4. China pubmed.ncbi.nlm.nih.gov

[Identification and isolation of mesenchymal stem cells from human fetal pancreas]. [2006]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Cell therapy for destructive pancreatitis]. [2022]

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

The safety of MSC therapy over the past 15 years: a meta-analysis. [2021]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Transient Fever: the Sole Treatment-Related Adverse Event associated with Mesenchymal Stromal Cells and Solid Clues from the Real World. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cell therapy for acute and chronic pancreatitis. [2021]

9. Turkey pubmed.ncbi.nlm.nih.gov

Stem cell therapy: a potential for the perils of pancreatitis. [2021]