Autologous Mesenchymal Stromal Cells and Islet Co-transplantation in TP-IAT
Study Details
Study Description
Brief Summary
This is a clinical trial for non-diabetic 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 (20x106/patient, or 50x106/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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Change in Islet Cell Function [1 year]
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.
Secondary Outcome Measures
- Change in HbA1C levels from baseline to 12 months. [1 year]
Change in HbA1C levels from baseline to 12 months
- Proportion of insulin-independent patients following IAT [1 year]
Proportion of insulin-independent patients following IAT
- Average daily insulin requirement [1 year]
Average daily insulin requirement
- Beta cell function as assessed by beta-score [1 year]
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.
Other Outcome Measures
- Change in islet function between baseline to day 90±28 [90 days]
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.
- Daily oral Morphine Equivalents on day prior to visit [9 months]
Daily oral Morphine Equivalents on day prior to visit (day 90±28 to day 365±28)
- Proportion of patients remaining on narcotics [9 months]
Proportion of patients remaining on narcotics (day 90±28 to day 365±28).
- Short form (SF)-12 Quality of Life score [1 year]
SF-12 Quality of Life score, Scores range from 0 to100, with higher scores indicating better physical and mental healthy functioning.
- 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]
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.
- Incidence and severity of adverse events and serious adverse events [1 year]
Incidence and severity of adverse events and serious adverse events
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of CP and scheduled for TP-IAT;
-
≥18 years old;
-
Diabetes-free before surgery as defined by the standards of the American Diabetes Association*.
-
No previous major pancreatic surgeries. Patients who have had minor surgeries including transduodenal sphincteroplasty or Whipple/Beger procedure are eligible.
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);
-
Patients who have had prior pancreatic surgeries including distal pancreatectomy or lateral pancreaticojejunostomy. We have observed that islet yield and function are negatively correlated with these types of pancreatic surgeries.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
Sponsors and Collaborators
- Medical University of South Carolina
- 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
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Pro00099487
- R01DK126454