Clinical trial NCT03779139: Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis
Official title: A Randomized Trial of Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Pancreatitis
Diabetes Mellitus
Islet Cell Transplantation
Keywords: total pancreatectomy with islet autotransplant
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2018-12-19
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized pilot trial of patients (n=30) undergoing Total Pancreatectomy and Islet AutoTransplant (TPIAT). Patients with islet harvest of greater than 5000 islet equivalents/kg body weight will be randomized to receive a portion of their islets into an omental pouch. For outcomes related to islet function, a group of normal volunteers (n=15) will be studied as a comparator group.

Detailed description: Chronic pancreatitis affects as many as 1 in every 2,500 persons and is associated with incapacitating pain, frequent hospitalization and risk of narcotic dependence. This is a debilitating disease with limited treatment options; afflicted patients are often young or middle aged adults. The health and economic costs of pancreatitis are great. Nearly $300 million is spent on emergency department visits alone in the US each year. More than 90% of patients with chronic pancreatitis have been hospitalized, half use narcotic analgesics regularly, and one-fourth are on disability. The lifetime risk of diabetes mellitus is as high as 70%. This proposal addresses needs in two broad topic areas: pancreatitis, and diabetes. The investigators propose to investigate a new technique for implanting autologous pancreatic islet cells into patients undergoing surgery for acute recurrent or chronic pancreatitis in an effort to improve long-term diabetes control.

Eligibility criteria: Inclusion Criteria:

1. Age 18-68
2. Scheduled for total pancreatectomy and IAT at U of MN. All patients who are approved for pancreatectomy and IAT at U of MN are reviewed by a multi-disciplinary committee including surgeons, gastroenterologists specializing in pancreatic disease, a pain specialist psychologist, and endocrinologist to confirm the diagnosis of chronic pancreatitis and candidate suitability for surgery.
3. Able to provide informed consent

Exclusion Criteria:

1. Pre-Existing diabetes mellitus fasting blood glucose\>115mg/dl, or hemoglobin A1c level \>6.0% because these are all evidence of inadequate beta-cello mass.
2. Use of any of the following treatments in the 30 days prior to enrollment: insulin, metformin, sulfonylureas, glinides, thiazolidinediones, GLP-1 agonists, DPP-4 inhibitors, or amylin.
3. ALT or AST\>2.5 times the upper limit of normal (ULN). Bilirubin\>ULN, unless due to benign diagnosis such as Gilbert's.
4. Any of the following hematologic abnormalities: server anemia (hemoglobin \<10 g/dL), thrombocytopenia (\<150/mm3), or neutropenia(\<1.0 x 109/L).
5. Current use or expected use of oral or injected corticosteroids, or any mediation likely to affect glucose tolerance. However, use of hydrocortisone for physiologic replacement, or use of any topical, inhaled or intranasal glucocorticoid is permitted.
6. Current or expected use of any other immunosuppressive agent.
7. Known coagulopathy, or need for anticoagulant therapy preoperatively (coumadin, enoxaparin), or any history of pulmonary embolism.
8. For females, plans to become pregnant or unwillingness to use birth control for the study duration.
9. Inability to comply with the study protocol.
10. Untreated psychiatric illness that may interfere with ability to give informed consent, or other developmental delay or neurocognitive disorder that impairs with a patient's ability to consent on their own behalf.
11. Any other medical condition that , in the opinion of the investigator, may interfere wit the patient's ability to successfully and safely complete the trial.

Primary outcomes:
measure: Portal vein thrombosis
timeFrame: Post operative day 4 or 5.
measure: Clavien-Dindo classification of surgical complications
timeFrame: Within 30 days of surgery
measure: Mixed Meal Tolerance Test
timeFrame: 1 year
measure: Intravenous Glucose tolerance test
timeFrame: 1 year
measure: Glucose potentiated arginine stimulation
timeFrame: 1 year
measure: Hypoglycemic clamp
timeFrame: 1 year
measure: Continuous glucose monitoring
timeFrame: 1 year
measure: Hemoglobin A1c levels
timeFrame: 1 year
measure: Insulin Use
timeFrame: 1 year
measure: Hypoglycemic episodes
timeFrame: 1 year
measure: Clarke score
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota, Department of Surgery
name: Greg Beilman, MD
role: PRINCIPAL_INVESTIGATOR
References: