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

Phase

Condition

Pain

Primary Biliary Cholangitis

Chronic Pain

Treatment

Mesenchymal Stem Cells

Other: Placebo

Clinical Study ID

NCT06205342

PRO 00132905

1UG3DK136705-01

Ages 18-75
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Age between 18 and 75 years old, male or female
Definite chronic pancreatitis, using M-ANNHEIM criteria
Patients who are diagnosed with painful CP for more than 6 months may be constant ormay have been waxing and waning/remitting.
Baseline Izbicki pain score > 30
Stable dose of opioids for the past 30 days

Exclusion

Exclusion criteria:

Acute pancreatitis per 2012 revised Atlanta criteria within the last 30 days. The revised Atlanta classification requires that two or more of the followingcriteria be met for the diagnosis of acute pancreatitis:
abdominal pain suggestive of pancreatitis,
serum amylase or lipase level greater than three times the upper normal value,or
characteristic imaging findings.
Chronic pain syndromes other than pancreatitis that require daily use of opioids inthe past 30 days.
Severe organ failure(s) likely to interfere with clinical pain outcomes within 6months.
HbA1c >12%
Laboratory values of WBC < 2.0 cells/10^3, HgB < 8gm/dl and platelets < 50K, AST orALT >3 times the upper limit of normal, and Creatine> 2.0mg/dl. Laboratory valuatemay be retested at a later date and if they are no longer exclusionary, the subjectmay be enrolled.
New York Heart Association grade 3 congestive heart failure.
Current lung, hematologic, or solid organ malignancy other than skin or cervicalStage 1 cancers within the past 3 years.
Subjects with current infection with Hepatitis B, C or HIV infection.
Active malignancy with the exception of non-melanoma skin cancer.
Subjects who have had any ongoing alcohol abuse and/or any illegal drug abuse withinthe past 6 months.
Any subject who has received an investigational drug or device within 30 days beforerandomization or who is expected to receive an investigational drug or device duringthis study.
Patients with planned endoscopic or surgical intervention, surgical resection orneedle drainage of pancreatic structures in the next 6 months.

Cases where participants initially meet inclusion criteria, but subsequentlyare felt to need a surgical or endoscopic intervention during the study will bereviewed by the medical monitor - as providing optimal care to the patient isthe priority. Individuals who do receive these interventions during their 6-month participation in the study will be censored from outcome evaluation.

Patients who have had a pancreatic surgery, endoscopic procedure with therapy, orhospitalization related to pancreatitis within the last 90 days.

In the case that a patient is screen-failed due to this criterion, they may bere-screened after the 90-day period has ended if all other eligibility criteriaare met.

Subjects with infected pancreatic pseudocysts or pancreatic walled-off necroticareas at the time of consent
Females who are pregnant or women of childbearing potential (WOCBP) and males withfemale partners of childbearing potential who are not willing to use adequatecontraception during the study
Breastfeeding females
Subject unwilling to follow the protocol and assessments

Study Design

Mesenchymal Stem Cells

July 17, 2024

June 01, 2028

Study 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.

Connect with a study center

Medical University of South Carolina
Charleston, South Carolina 29425
United States
Active - Recruiting

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