Cellular Therapy for Chronic Pancreatitis Pain

(MSCPainRelief Trial)

Overseen By Heather N Allen

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: VA Office of Research and Development

Must be taking: Opioids

Must not be taking: Antibiotics

Disqualifiers: Acute pancreatitis, Chronic pain syndromes, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to have a stable dose of opioids for the past 30 days, so you may need to maintain your current opioid medication if you are taking it. The protocol does not specify other medication restrictions.

What data supports the effectiveness of the treatment Mesenchymal stem cells for chronic pancreatitis pain?

Research shows that mesenchymal stem cells (MSCs) can reduce inflammation and pain in chronic pancreatitis, as seen in animal studies. MSCs have been effective in reducing pain and preserving pancreatic health in experimental models, suggesting potential benefits for chronic pancreatitis pain management. ^{1 2 3 4 5}

Is cellular therapy using mesenchymal stem cells safe for humans?

Mesenchymal stem cells (MSCs) have been studied for their ability to reduce inflammation in various conditions, including pancreatitis, and are generally considered safe in humans. They have been used in treatments for other diseases like inflammatory bowel disease and liver cirrhosis, showing potential without major safety concerns. ^{1 2 3 6 7}

How is the treatment with mesenchymal stem cells different from other treatments for chronic pancreatitis pain?

This treatment uses mesenchymal stem cells (MSCs), which are unique because they can reduce inflammation and aid in tissue regeneration, potentially offering pain relief and healing for chronic pancreatitis where no standard treatment exists. MSCs have been shown to have anti-inflammatory effects and can help preserve pancreatic tissue, making them a novel option compared to traditional pain management methods. ^{1 2 3 4 5}

What is the purpose of this trial?

The goal of this clinical trial is to test whether adult stem cells, called mesenchymal stem cells (MSCs) collected from the patient's bone marrow can help reduce pain caused by chronic pancreatitis and improve pancreatic function.

Research Team

Hongjun N Wang, PhD

Principal Investigator

Ralph H. Johnson VA Medical Center, Charleston, SC

Eligibility Criteria

This trial is for adults aged 18-75 with chronic pancreatitis, experiencing pain for over 6 months and on a stable opioid dose. They must have certain pancreatic conditions confirmed by M-ANNHEIM criteria but can't join if they've had acute pancreatitis recently, high opioid risk, severe anemia or liver issues, uncontrolled diabetes, heart failure, are pregnant/breastfeeding or unwilling to use contraception.

Inclusion Criteria

Your pain score is higher than 50 before starting the study.

My pancreas shows signs of severe damage or changes.

I have had chronic pancreatitis pain for over 6 months.

Exclusion Criteria

I have had cancer before, but it was either skin cancer or treated early and surgically.

I am scheduled for a procedure on my pancreas within the next 6 months.

I am not pregnant or willing to use birth control during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either mesenchymal stem cells (MSCs) or placebo to assess pain outcomes

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in quality of life and pancreatic volume

6 months

Long-term Follow-up

Participants are further monitored for changes in quality of life, pancreatic volume, and opioid use

12 months

Treatment Details

Interventions

• Mesenchymal stem cells

Trial Overview The study tests mesenchymal stem cells from the patient's bone marrow against a placebo to see if they reduce pain and improve pancreatic function in those with chronic pancreatitis. Participants will be randomly assigned to receive either the stem cells or 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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

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]

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]

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]

hAAT-MSCs (mesenchymal stromal cells overexpressing human alpha-1 antitrypsin) showed better preservation of pancreatic morphology and reduced pain sensitivity in chronic pancreatitis (CP) mouse models compared to native MSCs, indicating their potential for improved treatment outcomes.

Both hAAT-MSCs and native MSCs effectively reduced abdominal pain and inflammation in CP, but hAAT-MSCs demonstrated a trend towards greater pain relief and better pancreatic health, suggesting they may offer enhanced therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells. Chow, RP., Nguyen, K., Gou, W., et al.[2022]

Mesenchymal stem cells (MSCs) show promise in treating acute pancreatitis (AP) due to their anti-inflammatory effects and ability to repair tissue damage, which is crucial as AP cases are rising globally and can lead to severe complications.

Induced mesenchymal stem cells (iMSCs) offer a standardized preparation method and large-scale production potential, making them a more viable option for commercialization compared to MSCs from varied sources like bone marrow or umbilical cord blood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of diagnosis and Mesenchymal stem cells therapy for acute pancreatitis. Munir, F., Jamshed, MB., Shahid, N., et al.[2023]

Bone marrow mesenchymal stem cells (bmMSCs) significantly reduced pancreatic injury and associated lung damage in a rat model of acute pancreatitis, as evidenced by lower levels of inflammatory cytokines and improved pancreatic histology.

The protective effects of bmMSCs are linked to their ability to regulate the release of inflammatory cytokines through the NF-κB p65 signaling pathway, although they do not actively migrate to the inflamed pancreas but are passively trapped in related organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of bone marrow mesenchymal stem cells in L-arg-induced acute pancreatitis: effects and possible mechanisms. Yin, G., Hu, G., Wan, R., et al.[2022]

References

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

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

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

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

3. Japan pubmed.ncbi.nlm.nih.gov

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

4. Turkey pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells. [2022]

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

Current status of diagnosis and Mesenchymal stem cells therapy for acute pancreatitis. [2023]

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

Role of bone marrow mesenchymal stem cells in L-arg-induced acute pancreatitis: effects and possible mechanisms. [2022]