Clinical trial NCT05095532: Autologous Mesenchymal Stromal Cells and Islet Co-transplantation in TP-IAT
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Chronic Pancreatitis
Mesenchymal Stem Cells
Keywords: Total Pancreatectomy
TP-IAT
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2021-10-27
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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);

Primary outcomes:
measure: Change in Islet Cell Function
timeFrame: 1 year
Secondary outcomes:
measure: Change in HbA1C levels from baseline to 12 months.
timeFrame: 1 year
measure: Proportion of insulin-independent patients following IAT
timeFrame: 1 year
measure: Average daily insulin requirement
timeFrame: 1 year
measure: Beta cell function as assessed by beta-score
timeFrame: 1 year
Other outcomes:
measure: Change in islet function between baseline to day 90±28
timeFrame: 90 days
measure: Daily oral Morphine Equivalents on day prior to visit
timeFrame: 9 months
measure: Proportion of patients remaining on narcotics
timeFrame: 9 months
measure: Short form (SF)-12 Quality of Life score
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
measure: Incidence and severity of adverse events and serious adverse events
timeFrame: 1 year
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Charlton Strange, M.D
role: STUDY_DIRECTOR
affiliation: Medical University of South Carolina
name: William Lancaster, M.D
role: STUDY_DIRECTOR
affiliation: Medical University of South Carolina
name: Hongjun Wang
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
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.
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.