Safety and Efficacy of Mesenchymal Stem Cells Associated With Chronic Pancreatitis Pain

Chronic Pain Clinical Trial

— STEMCAP-1  

Official title:

STEMCAP-1: Safety and Efficacy of Mesenchymal Stem Cells Associated With Chronic Pancreatitis Pain

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06205342
• Other study ID #: PRO 00132905
• Secondary ID: 1UG3DK136705-01
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: August 1, 2024
• Est. completion date: May 1, 2028

Study information

• Verified date: June 2024
• Source: Medical University of South Carolina
• Contact: Hongjun Wang, Ph.D.
• Phone: 843-792-1800
• Email: wangho[@]musc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Chronic pancreatitis (CP) and chronic pain: CP is a debilitating disease characterized by persistent pancreatic inflammation, irreversible morphological changes (fibrosis) in the pancreas and severe chronic pain. A progressive loss of exocrine and endocrine function occurs during disease progression. The incidence of CP ranges from 1.6 to 23 cases per 100,000 populations per year worldwide and is likely under diagnosed in the general population. CP in the United States results in more than 122,000 outpatient visits and more than 56,000 hospitalizations per year. The poorly understood pathophysiology of CP makes the identification of means to treat the underlying cellular disorder problematic. Abdominal pain has been reported in at least 80-94% of patients. The pain suffered by CP patients is among the worst encountered in medicine, which often leads to opioid addiction. Many CP patients require hospital admission at some stage in their illness. The cause of pain is complex and is mostly unknown. The pathophysiology in pain due to CP is multifactorial, including peripheral nociception, peripheral/pancreatic neuropathy, and neuroplasticity. Achieving satisfactory pain relief remains a challenge. Current management strategies have used a step-up approach in pain medications that often lead to opioid dependence. Among all patients, 40-75% patients will eventually require surgery, after which only 34-52% attain pain relief after pancreas resection. CP pain provides a useful model for the understanding of the mechanisms and treatment of pain syndromes with an identifiable nociceptive source in general as approximately 50 million U.S. adults are suffering from pain. Improving the management of CP pain may translate to other disease states with pain and opioid addiction.

Mesenchymal stromal cells (MSCs) are adult stem cells that can be harvested and expanded for therapy. MSC therapy is an investigational intervention for CP. There is increasing evidence that MSC therapy can effectively target several injury pathways in a variety of fibroinflammatory diseases and can reduce pain while suppressing inflammation, something that most pharmacological interventions cannot accomplish. Data from animal models and clinical trials support the outstanding and durable effects of MSC infusion in the suppression of chronic neurological pain and inflammation associated with knee osteoarthritis, critical limb ischemia, neuropathy, diabetic neuropathy, and others. MSCs migrate to the spinal cord and pre-frontal cortex of neuropathic mice after injection and exert pain relief. A recent study demonstrated that infusion of human MSCs significantly reduced pain, improved pancreatic volume, and reduced fibrosis in CP rodent models.

Rationale of the study: Because MSCs are a novel therapy that may improve chronic pancreatitis pain in animal models and improve chronic pain in other human disease states, these cells are worthy of study. This pilot study will give participants MSCs or placebo for CP subjects with pain. This study will inform future study designs and may lead to MSCs as a standard of care if they are safe and effective.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: May 1, 2028
• Est. primary completion date: October 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age between 18 and 75 years old, male or female

2. Definite chronic pancreatitis (stage 1-3)

3. Patients who are diagnosed with painful CP for more than 6 months may be constant or may have been waxing and waning/remitting.

4. Baseline Izbicki pain score > 30

5. Stable dose of opioids for the past 30 days

Exclusion Criteria:

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

• The revised Atlanta classification requires that two or more of the following criteria be met for the diagnosis of acute pancreatitis: (a) abdominal pain suggestive of pancreatitis, (b) serum amylase or lipase level greater than three times the upper normal value, or (c) characteristic imaging findings.

2. Score >7 on the Opioid Risk Tool

3. Chronic pain syndromes other than pancreatitis that require daily use of opioids in the past 30 days.

4. Severe organ failure(s) likely to interfere with clinical pain outcomes within 6 months.

5. HbA1c >10%

6. Active malignancy with the exception of non-melanoma skin caner.

7. TWEAK score > 2 points at screening.

8. Any subject who has received an investigational drug or device within 30 days before randomization or who is expected to receive an investigational drug or device during this study.

9. Patients with planned endoscopic or surgical intervention, surgical resection or needle drainage of pancreatic structures in the next 6 months.

10. Subjects with infected pancreatic pseudocysts or pancreatic walled-off necrotic areas at the time of consent

11. Females who are pregnant or women of childbearing potential (WOCBP) and males with female partners of childbearing potential who are not willing to use adequate contraception during the study

12. Breastfeeding females

13. Subject unwilling to follow the protocol and assessments

Related Conditions & MeSH terms

• Chronic Pain
• Chronic Pancreatitis
• Pancreatitis
• Pancreatitis, Chronic

Intervention

Drug:
• Mesenchymal Stem Cells
Autologous bone marrow derived MSCs

Other:
• Other: Placebo
Control

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Izbicki pain score (M6 vs. Baseline)	Change in pain as measured by Izbicki pain scores, a validated score for pain in chronic pancreatitis, consist of 4 questions, with a range of 0 (no pain) to 100 (severe, debilitating pain).	6 months
Secondary	Change in pancreatic volume measured by blinded scoring of MRI	Pancreas volume change	Screening, 6 month
Secondary	Change in opioid use as measured in average daily morphine equivalents.	Average Daily morphine Equivalent	Screening, 1 month, 3 month, 6 month
Secondary	Changes in quality of life	Quality of life to be measured by Promise-29-v 2.1 (with generated T-score for each domain)	Screening, 1 month, 3 month, 6 month
Secondary	Change in M-Manheim Severity Index absolute score	Severity of Index absolute scores (with lowest severity 0 and highest severity 24 points)	Screening, 1 month, 3 month, 6 month