Clinical trial NCT02384018: Mesenchymal Stem Cell and Islet Co-transplantation
Official title: A Phase I Study Evaluating Safety and Tolerability of Autologous Bone Marrow-derived Mesenchymal Stromal Cells in Chronic Pancreatitis Patients Who Undergo Total Pancreatectomy and Islet Autotransplantation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Pancreatitis
Diabetes
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2015-03-10
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to show safety and tolerability to our mesenchymal stromal cells (MSCs) product which will be autologous in nature, expanded using a non-xenogeneic, human component expansion media (pooled human platelet lysate) and delivered fresh. Subsequently, the investigators intend to test whether infusion of MSCs immediately after islet autograft can reduce onset of diabetes and improve glycemic control after total pancreatectomy and islet autotransplantation.

Detailed description: This is a Phase I study evaluating safety and tolerability of autologous BM-MSCs in chronic pancreatitis patients who undergo total pancreatectomy and islet autotransplantation (TP-IAT). CCT-BMMSC will be infused at one of the following doses: (Tier 1), 20x10\^6 cell per patient, (Tier 2), 50x10\^6 cell per patient, and (Tier 3), 100x10\^6 cell per patient.

Primary objective: To describe and compare the safety and tolerability of infusion of fresh autologous bone marrow-derived Mesenchymal stromal cells after islet transplantation in chronic pancreatitis patients who undergo TP-IAT. The investigators plan to enroll 24 patients for the whole study. The duration of this study is 12 months. The investigators anticipate that this study will be completed within 2 years of commencement.

Secondary objective: Efficacy of infusion of fresh autologous bone marrow-derived Mesenchymal stromal cells together after islet transplantation in chronic pancreatitis patients who undergo TP-IAT as assessed through onset of diabetes, glycemic control, pain relief and quality of life index.

Safety variables: Adverse events (AEs), Laboratory parameters (hematology, biochemistry, urinalysis), Vital signs

Eligibility criteria: Inclusion Criteria:

* Chronic pancreatitis patients who undergo TP-IAT.
* \>18 years of age.
* Patients with BMI from 18.5 to 30.
* Renal function: \>90mls/min/1.73m squared
* Normal INR/PT/PTT values for MUSC clinical laboratory standards
* Diabetes free before surgery (fasting blood glucose\<125mg/dl).
* No prior pancreatic surgery with the exception of transduodenal sphincteroplasty or Whipple/Beger procedure.
* Patients with normal liver function as measured by serum levels of aminotransferase including alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and total bilirubin levels.

Exclusion Criteria:

* Patients whose Hemoglobin, Hematocrit, and Platelet count are above or below normal values for MUSC clinical laboratory standards.
* Patients who has hematological malignancy.
* Patients who are under immunosuppression.
* Patients with marked calcification disease on CT scan.
* Patients with severe fibrosis and atrophy on pancreas MRI.

Primary outcomes:
measure: C-peptide level after mixed meal tolerance test
timeFrame: 12 months
Secondary outcomes:
measure: Liver function, kidney function
timeFrame: 12 months after transplant
measure: The absence of severe hypoglycemic episodes
timeFrame: 12 months after transplant
Other outcomes:
Locations:
city: Charleston
country: United States
facility: GI Surgery, Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Hongjun Wang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang H, Strange C, Nietert PJ, Wang J, Turnbull TL, Cloud C, Owczarski S, Shuford B, Duke T, Gilkeson G, Luttrell L, Hermayer K, Fernandes J, Adams DB, Morgan KA. Autologous Mesenchymal Stem Cell and Islet Cotransplantation: Safety and Efficacy. Stem Cells Transl Med. 2018 Jan;7(1):11-19. doi: 10.1002/sctm.17-0139. Epub 2017 Nov 21.