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

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.

• Change in pancreatic volume measured by blinded scoring of MRI [Срок оценки: Screening, 6 month]
• Change in opioid use as measured in average daily morphine equivalents. [Срок оценки: Screening, 1 month, 3 month, 6 month]
• Changes in quality of life [Срок оценки: Screening, 1 month, 3 month, 6 month]
• Change in M-Manheim Severity Index absolute score [Срок оценки: Screening, 1 month, 3 month, 6 month]