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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Mesenchymal Stem Cells; Chronic Pancreatitis
• Intervention / Treatment: Biological: Bone marrow-derived mesenchymal stem cells; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kelsey Cook; Phone Number: 843 876 0420; Email: conder@musc.edu
• Study Contact Backup: Name: Leah Benn, MPH; Phone Number: 843-792-2813; Email: bennle@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Leah Benn, MPH; Phone Number: 843-792-2813; Email: bennle@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in islet function between baseline to day 90±28	Change in islet function between baseline to day 90±28. Islet function will be indicated by area under the curve of C-peptide levels during a mixed meal tolerance test adjusted by islet equivalent number transplanted.	90 days
Daily oral Morphine Equivalents on day prior to visit	Daily oral Morphine Equivalents on day prior to visit (day 90±28 to day 365±28)	9 months
Proportion of patients remaining on narcotics	Proportion of patients remaining on narcotics (day 90±28 to day 365±28).	9 months
Short form (SF)-12 Quality of Life score	SF-12 Quality of Life score, Scores range from 0 to100, with higher scores indicating better physical and mental healthy functioning.	1 year
Glycemic control measured by area under the curve (AUC) HbA1c through year 1 and the C-peptide AUC and HbA1c AUC through year 1 (measured every three months) as impacted in a multivariate model by the IEQ/kg islets transplanted.	Glycemic control measured by area under the curve (AUC) HbA1c through year 1 and the C-peptide AUC and HbA1c AUC through year 1 (measured every three months) as impacted in a multivariate model by the IEQ/kg islets transplanted.	1 year
Incidence and severity of adverse events and serious adverse events	Incidence and severity of adverse events and serious adverse events	1 year

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Study Director: Charlton Strange, M.D, Medical University of South Carolina; Study Director: Katherine Morgan, M.D, Medical University of South Carolina; Principal Investigator: Hongjun Wang, Medical University of South Carolina

Publications and helpful links

General Publications

• Sutherland DE, Gruessner AC, Carlson AM, Blondet JJ, Balamurugan AN, Reigstad KF, Beilman GJ, Bellin MD, Hering BJ. Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes. Transplantation. 2008 Dec 27;86(12):1799-802. doi: 10.1097/TP.0b013e31819143ec.
• Morgan KA, Lancaster WP, Owczarski SM, Wang H, Borckardt J, Adams DB. Patient Selection for Total Pancreatectomy with Islet Autotransplantation in the Surgical Management of Chronic Pancreatitis. J Am Coll Surg. 2018 Apr;226(4):446-451. doi: 10.1016/j.jamcollsurg.2017.12.018. Epub 2017 Dec 28.
• Wang J, Zhang Y, Cloud C, Duke T, Owczarski S, Mehrotra S, Adams DB, Morgan K, Gilkeson G, Wang H. Mesenchymal Stem Cells from Chronic Pancreatitis Patients Show Comparable Potency Compared to Cells from Healthy Donors. Stem Cells Transl Med. 2019 May;8(5):418-429. doi: 10.1002/sctm.18-0093. Epub 2019 Jan 24.
• Song L, Sun Z, Kim DS, Gou W, Strange C, Dong H, Cui W, Gilkeson G, Morgan KA, Adams DB, Wang H. Adipose stem cells from chronic pancreatitis patients improve mouse and human islet survival and function. Stem Cell Res Ther. 2017 Aug 30;8(1):192. doi: 10.1186/s13287-017-0627-x.
• Ryan EA, Paty BW, Senior PA, Lakey JR, Bigam D, Shapiro AM. Beta-score: an assessment of beta-cell function after islet transplantation. Diabetes Care. 2005 Feb;28(2):343-7. doi: 10.2337/diacare.28.2.343.
• Wang H, Desai KD, Dong H, Owzarski S, Romagnuolo J, Morgan KA, Adams DB. Prior surgery determines islet yield and insulin requirement in patients with chronic pancreatitis. Transplantation. 2013 Apr 27;95(8):1051-7. doi: 10.1097/TP.0b013e3182845fbb.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Total Pancreatectomy; TP-IAT
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Pancreatic Diseases; Chronic Disease; Pancreatitis; Pancreatitis, Chronic
• Other Study ID Numbers: Pro00099487; R01DK126454 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No