Autologous Mesenchymal Stromal Cells and Islet Co-transplantation in TP-IAT

Study Overview
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Brief Summary
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This is a clinical trial for chronic pancreatitis (CP) patients undergoing total pancreatectomy with islet autotransplantation (TP-IAT). Participants will be randomized to either bone marrow-derived mesenchymal stem cells (MSCs) or control with the standard of care. Participants will be followed for one-year post-transplant.

Detailed Description
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This will be a randomized, controlled clinical trial for CP patients scheduled to undergo a TP-IAT surgery. Those who are consented will be randomized into one of three groups. One group will receive islet transplantation alone, a placebo. The other two groups will receive islets plus autologous bone marrow-MSCs at two different doses (20x10^6/patient, or 50x10^6/patient). The TP-IAT procedure will remain as routinely performed. Patients will be followed for12 months post-transplantation, having 3 follow-up visits scheduled on days 90, 180, and 365 after the transplant. The primary endpoint will be a change in islet function from baseline to 12 months post-transplantation as measured by the C-peptide area under the curve following a mixed meal tolerance test. Potential effects of MSCs on glycemic control, pain relief, quality of life, and adverse events will be evaluated at each follow-up visit.

Official Title
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Autologous Mesenchymal Stromal Cells and Islet Co-transplantation to Enhance Islet Survival and Function in Chronic Pancreatitis Patients Undergo Total Pancreatectomy and Islet Autotransplantation

Conditions
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Chronic Pancreatitis, Mesenchymal Stem Cells

Intervention / Treatment
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* Biological: Bone marrow-derived mesenchymal stem cells
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CP and scheduled for TP-IAT; ≥18 years old; Diabetes with HbA1c <12%. Exclusion Criteria: Patients who are under immunosuppression; Pregnant and breastfeeding women. Patients who have liver damage based on ALT, AST, and total bilirubin levels (>3 times normal levels);

Ages Eligible for Study
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Minimum Age: 18 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 will be a randomized, controlled clinical trial in which CP patients scheduled for TP-IAT who meet the study criteria and consented will be randomized into three groups. One group will receive islet transplantation alone (n=14). The other two groups will receive islets plus BM-MSCs at two different doses (20x10^6/patient, or 50x10^6/patient, n=14 in each group).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BM-MSCs at 20x10^6<br>One time infusion of islets plus BM-MSCs at 20x10^6/patient, n=14 | Biological: Bone marrow-derived mesenchymal stem cells<br>* MSC transplantation<br>|
| Experimental: BM-MSCs at 50x10^6<br>One time infusion of islets plus BM-MSCs at 50x10^6/patient, n=14 | Biological: Bone marrow-derived mesenchymal stem cells<br>* MSC transplantation<br>|
| Placebo Comparator: Placebo<br>One time infusion of islets only. | Other: Placebo<br>* Standard of Care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Islet Cell Function | The primary endpoint will be change in islet function between baseline and 12 months as measured by area under the curve of C-peptide levels during a mixed meal tolerance test (MMTT) adjusted by islet equivalent number (IEQ) transplanted. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1C levels from baseline to 12 months. | Change in HbA1C levels from baseline to 12 months | 1 year | 
| Proportion of insulin-independent patients following IAT | Proportion of insulin-independent patients following IAT | 1 year | 
| Average daily insulin requirement | Average daily insulin requirement | 1 year | 
| Beta cell function as assessed by beta-score | β-score is an assessment of beta cell function after islet transplantation incorporating fasting plasma glucose levels, HbA1c, daily insulin, and stimulated c-peptide. The range of the score is from 0 to 8. Higher number means better beta cell transplant function. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Total Pancreatectomy, TP-IAT