Novel Cellular Therapy for the Treatment of Pain Associated With Chronic Pancreatitis

Study Overview
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Brief Summary
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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.

Detailed Description
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Chronic pain affects approximately 50 million U.S. adults and disproportionally impacts about 20 million veterans; 1 in 3 Veterans have been diagnosed with a condition related to chronic pain. There is also a significant interaction between chronic pain, post-traumatic stress disorder (PTSD), and persistent post-concussive syndromes common to the veteran population. The opioids that are prescribed to treat chronic pain are often ineffective and are associated with a significantly increased risk of misuse, addiction, diversion, overdose, and death. Unconventional treatment options that can effectively manage pain and avoid or reduce opioid addiction in Veterans are of significant clinical importance to VA healthcare. Given the high morbidity and mortality attributable to pain therapy, not to mention the staggering medical cost, it is vital to the VA healthcare mission to explore novel strategies to treat chronic pain effectively. Chronic pancreatitis (CP) is an inflammatory disease characterized by pancreatic inflammation, fibrosis, and abdominal pain. CP subjects often suffer extreme pain, which often leads to opioid addiction. In our animal models, the investigators show a linkage between inflammatory increases in neuropeptides and pain. In humans, the investigators have more specific pain measurements to explore the link between inflammation, neuropeptides, and neuropathic pain measurement as impacted by a novel therapeutic. Mesenchymal stromal cells (MSCs) are adult stem cells that can be harvested and expanded for therapy. MSC therapy represents a promising new intervention as increasing evidence demonstrates 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. Rationale of the study: Because MSCs are a novel therapy that my improve chronic pancreatitis pain in animal models and improve chronic pain in other human disease states, these cells are worthy of study. Specifically, the investigators propose a pilot phase 1 crossover study design in which MSCs or placebo are prospectively given to CP subjects with pain outcomes measured. This phase 1 study will inform future study designs and may lead to MSCs as a standard of care if they are safe and effective.

Official Title
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Novel Cellular Therapy for the Treatment of Pain Associated With Chronic Pancreatitis

Conditions
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Chronic Pancreatitis, Chronic Pain

Intervention / Treatment
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* Drug: Mesenchymal stem cells
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 75 years old, male or female Definite chronic pancreatitis (stage 1-3) by M-ANNHEIM criteria One or more of the following are required: Pancreatic calcifications Moderate or marked ductal lesions Marked and persistent exocrine insufficiency defined as pancreatic steatorrhea markedly reduced by enzyme supplementation Typical histology of an adequate histological specimen Patients who are diagnosed with painful CP for more than 6 months may be constant or may have been waxing and waning/remitting. Baseline Izbicki pain score > 50 Stable dose of opioids for the past 30 days Exclusion Criteria: Acute pancreatitis per 2012 revised Atlanta criteria within the last 30 days Score >7 on the Opioid Risk Tool Chronic pain syndromes other than pancreatitis that require daily use of opioids in the past 30 days. Hemoglobin of <8.0g/dL, EGFR<60 ml/min, AST or ALT >2 times upper limit of normal, Bilirubin > 1.5 mg/dl unless the subject has confirmed Gilbert syndrome., Platelets <100,000/microliter, HbA1c >10% Congestive Heart Failure NYHA class >1 History of Malignancy except for in situ malignancies that have been surgically treated and basal cell skin cancers Evidence of active infection using current antibiotics or with Hepatitis B, C, or HIV Known intravenous contrast allergy causing anaphylaxis TWEAK score > 2 points at screening (24) (the questions below will be asked of the subjects at screening) 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. Patients with planned endoscopic or surgical intervention, surgical resection or needle drainage of pancreatic structures in the next 6 months. Subjects with infected pancreatic pseudocysts or pancreatic walled-off necrotic areas at the time of consent 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 Breastfeeding females Subject unwilling to follow the protocol and assessments

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of a single intravenous infusion of autologous bone marrow-derived mesenchymal stromal cells in subjects with painful chronic pancreatitis.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Cohort<br>MSC | Drug: Mesenchymal stem cells<br>* Autologous bone marrow derived MSCs<br>* Other names: MSCs;|
| Placebo Comparator: Validation Cohort<br>Placebo | Other: Placebo<br>* Controls<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Izbicki pain score (M6 vs. Baseline) | Change in pain as measured by Izbicki pain scores | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pancreatic volume measured by blinded scoring of MRI | Pancreas volume change | Screening, 6 months and 12 months | 
| Change in opioid use as measured in average daily morphine equivalents. | Average Daily morphine Equivalent. | Screening, 6 and 12 months | 
| Change in quality of life | Quality of life to be measured by Promise-29-v 2.1 | Screening, 6 and 12 months | 
| Change in M-Manheim Severity Index absolute score | Severity of Index absolute scores | Screening, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stem cells (MSCs), Chronic pancreatitis, Pain relief, Pancreas dysfunction, Fibrosis