Back to resultsIntra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis (iSite)
Primary Purpose
Chronic Pancreatitis, Diabetes Mellitus, Islet Cell Transplantation
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Intrahepatic islets and islets in the omental pouch
Intrahepatic islets alone
Normal Volunteers
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Pancreatitis focused on measuring total pancreatectomy with islet autotransplant
Eligibility Criteria
Inclusion Criteria:
- Age 18-68
- 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.
- Able to provide informed consent
Exclusion Criteria:
- 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.
- 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.
- ALT or AST>2.5 times the upper limit of normal (ULN). Bilirubin>ULN, unless due to benign diagnosis such as Gilbert's.
- Any of the following hematologic abnormalities: server anemia (hemoglobin <10 g/dL), thrombocytopenia (<150/mm3), or neutropenia(<1.0 x 109/L).
- 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.
- Current or expected use of any other immunosuppressive agent.
- Known coagulopathy, or need for anticoagulant therapy preoperatively (coumadin, enoxaparin), or any history of pulmonary embolism.
- For females, plans to become pregnant or unwillingness to use birth control for the study duration.
- Inability to comply with the study protocol.
- 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.
- 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.
Sites / Locations
- University of MinnesotaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Sham Comparator
Arm Label
Intrahepatic islets alone
Intrahepatic and omental pouch islets
Normal Volunteers
Arm Description
Outcomes
Primary Outcome Measures
Portal vein thrombosis
Portal vein thrombosis is associated with higher tissue volume infused into the portal vein and higher portal pressures and is assessed using abdominal ultrasound.
Clavien-Dindo classification of surgical complications
Grades surgical complications based on the level of treatment necessary to treat the complication.
Mixed Meal Tolerance Test
Patient is given Boost HP (6cc/kg), ingested 5 minutes after t=0 blood draw. Blood is drawn every half hour for 2 hours.
Intravenous Glucose tolerance test
Patients are given a bolus of 0.2mg/kg of dextrose at t=0. Blood samples will be drawn at t=-10,-5,-1,2,3,4,5,7 and 10 minutes
Glucose potentiated arginine stimulation
Starting immediately after glucose tolerance test (time t=10 minutes), 20% dextrose will be infused to maintain a glucose ~230mg/dL until test is completed. Glucose levels are measured every 5 minutes to maintain glucose in the target range after 40 minutes of continuous 20% dextrose infusion, After 40 minutes of continuous D20% infusion, baseline samples for glucose, insulin, and C-peptide are drawn (three samples over 10 minutes), a bolus of 5 grams arginine is given (at time 55 minutes), and samples for glucose, insulin, and C-peptide are taken at 2, 3, 4, and 5 minutes after
the arginine bolus.
Hypoglycemic clamp
A stepped hypoglycemic clamp protocol with variable glucose infusion rates will be performed to achieve 45 min glucose plateaus at 70, 60, and 50 mg/dl.Glucagon responses will be calculated by subtracting the mean of the three baseline values observed prior to the clamp from glucagon levels observed at 70, 60, and 50 mg/dl glucose nadirs during the clamp
Continuous glucose monitoring
3 days of CGM monitoring at one year will be obtained for mean glucose,standard deviation, and percent of time in hypo- and hyperglycemia
Hemoglobin A1c levels
Measure of average glucose levels over last several weeks
Insulin Use
calculated as units/kg/day, will be assessed from glucose and insulin diaries maintained by patients for 14 days, overlapping with day 90
Hypoglycemic episodes
All severe hypoglycemic events will be recorded. This is defined based on American Diabetes Association criteria as a hypoglycemic episode <54 mg/dL or (if not measured) associated with prompt recovery upon administration of glucose in which a patient is mentally or physically incapacitated and requires assistance from another person to treat the hypoglycemia.
Clarke score
is determined from eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia; it evaluates symptomatic responses to hypoglycemia. A score of 4 or greater suggests impaired awareness of hypoglycemia
Secondary Outcome Measures
Full Information
NCT ID
NCT03779139
First Posted
November 5, 2018
Last Updated
October 2, 2023
Sponsor
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT03779139
Brief Title
Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis
Acronym
iSite
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Pancreatitis, Diabetes Mellitus, Islet Cell Transplantation
Keywords
total pancreatectomy with islet autotransplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
45 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intrahepatic islets alone
Arm Type
Active Comparator
Arm Title
Intrahepatic and omental pouch islets
Arm Type
Experimental
Arm Title
Normal Volunteers
Arm Type
Sham Comparator
Intervention Type
Procedure
Intervention Name(s)
Intrahepatic islets and islets in the omental pouch
Intervention Description
Patients with islet harvest of >5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to 4000 IEq/kg delivered via intraportal route and the remainder implanted into a constructed omental pouch.
Intervention Type
Procedure
Intervention Name(s)
Intrahepatic islets alone
Intervention Description
This is the standard of care procedure. Patients with islet harvest of >5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to all islets autotransplanted intrahepatically via the intraportal route.
Intervention Type
Other
Intervention Name(s)
Normal Volunteers
Intervention Description
These individuals will undergo metabolic testing as well as islet cell function testing.
Primary Outcome Measure Information:
Title
Portal vein thrombosis
Description
Portal vein thrombosis is associated with higher tissue volume infused into the portal vein and higher portal pressures and is assessed using abdominal ultrasound.
Time Frame
Post operative day 4 or 5.
Title
Clavien-Dindo classification of surgical complications
Description
Grades surgical complications based on the level of treatment necessary to treat the complication.
Time Frame
Within 30 days of surgery
Title
Mixed Meal Tolerance Test
Description
Patient is given Boost HP (6cc/kg), ingested 5 minutes after t=0 blood draw. Blood is drawn every half hour for 2 hours.
Time Frame
1 year
Title
Intravenous Glucose tolerance test
Description
Patients are given a bolus of 0.2mg/kg of dextrose at t=0. Blood samples will be drawn at t=-10,-5,-1,2,3,4,5,7 and 10 minutes
Time Frame
1 year
Title
Glucose potentiated arginine stimulation
Description
Starting immediately after glucose tolerance test (time t=10 minutes), 20% dextrose will be infused to maintain a glucose ~230mg/dL until test is completed. Glucose levels are measured every 5 minutes to maintain glucose in the target range after 40 minutes of continuous 20% dextrose infusion, After 40 minutes of continuous D20% infusion, baseline samples for glucose, insulin, and C-peptide are drawn (three samples over 10 minutes), a bolus of 5 grams arginine is given (at time 55 minutes), and samples for glucose, insulin, and C-peptide are taken at 2, 3, 4, and 5 minutes after
the arginine bolus.
Time Frame
1 year
Title
Hypoglycemic clamp
Description
A stepped hypoglycemic clamp protocol with variable glucose infusion rates will be performed to achieve 45 min glucose plateaus at 70, 60, and 50 mg/dl.Glucagon responses will be calculated by subtracting the mean of the three baseline values observed prior to the clamp from glucagon levels observed at 70, 60, and 50 mg/dl glucose nadirs during the clamp
Time Frame
1 year
Title
Continuous glucose monitoring
Description
3 days of CGM monitoring at one year will be obtained for mean glucose,standard deviation, and percent of time in hypo- and hyperglycemia
Time Frame
1 year
Title
Hemoglobin A1c levels
Description
Measure of average glucose levels over last several weeks
Time Frame
1 year
Title
Insulin Use
Description
calculated as units/kg/day, will be assessed from glucose and insulin diaries maintained by patients for 14 days, overlapping with day 90
Time Frame
1 year
Title
Hypoglycemic episodes
Description
All severe hypoglycemic events will be recorded. This is defined based on American Diabetes Association criteria as a hypoglycemic episode <54 mg/dL or (if not measured) associated with prompt recovery upon administration of glucose in which a patient is mentally or physically incapacitated and requires assistance from another person to treat the hypoglycemia.
Time Frame
1 year
Title
Clarke score
Description
is determined from eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia; it evaluates symptomatic responses to hypoglycemia. A score of 4 or greater suggests impaired awareness of hypoglycemia
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
68 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age 18-68
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.
Able to provide informed consent
Exclusion Criteria:
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.
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.
ALT or AST>2.5 times the upper limit of normal (ULN). Bilirubin>ULN, unless due to benign diagnosis such as Gilbert's.
Any of the following hematologic abnormalities: server anemia (hemoglobin <10 g/dL), thrombocytopenia (<150/mm3), or neutropenia(<1.0 x 109/L).
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.
Current or expected use of any other immunosuppressive agent.
Known coagulopathy, or need for anticoagulant therapy preoperatively (coumadin, enoxaparin), or any history of pulmonary embolism.
For females, plans to become pregnant or unwillingness to use birth control for the study duration.
Inability to comply with the study protocol.
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.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kristine Mulier
Phone
612-625-0654
Email
groeh001@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Greg Beilman, MD
Organizational Affiliation
University of Minnesota, Department of Surgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Greg Beilman
Phone
612-625-7911
Email
beilm001@umn.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis
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