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

Chronic Pancreatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05095532
• Other study ID #: Pro00099487
• Secondary ID: R01DK126454
• Status: Recruiting
• Phase: Phase 1
• Start date: December 1, 2021
• Est. completion date: June 30, 2026

Study information

• Verified date: February 2024
• Source: Medical University of South Carolina
• Contact: Leah Benn, MPH
• Phone: 843-792-2813
• Email: bennle[@]musc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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);

Related Conditions & MeSH terms

• Chronic Pancreatitis
• Mesenchymal Stem Cells
• Pancreatitis
• Pancreatitis, Chronic

Intervention

Biological:
• Bone marrow-derived mesenchymal stem cells
MSC transplantation

Other:
• Placebo
Standard of Care

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Proportion of patients remaining on narcotics	Proportion of patients remaining on narcotics (day 90±28 to day 365±28).	9 months
Other	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
Other	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
Other	Incidence and severity of adverse events and serious adverse events	Incidence and severity of adverse events and serious adverse events	1 year
Primary	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	Change in HbA1C levels from baseline to 12 months.	Change in HbA1C levels from baseline to 12 months	1 year
Secondary	Proportion of insulin-independent patients following IAT	Proportion of insulin-independent patients following IAT	1 year
Secondary	Average daily insulin requirement	Average daily insulin requirement	1 year
Secondary	Beta cell function as assessed by beta-score	ß-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