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Completed

NCT Number: NCT03779139

Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis

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.

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Key information

Conditions

Chronic Pancreatitis Chronic Disease Diabetes Mellitus Digestive System Diseases Disease Attributes Endocrine System Diseases Glucose Metabolism Disorders Islet Cell Transplantation Metabolic Diseases Nutritional and Metabolic Diseases Pancreatic Diseases Pancreatitis Pancreatitis, Chronic Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–68 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Intrahepatic islets and islets in the omental pouch

Procedure

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.

Intrahepatic islets alone

Procedure

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.

Normal Volunteers

Other

These individuals will undergo metabolic testing as well as islet cell function testing.

Primary outcomes

  1. Portal vein thrombosis

    Time frame: Post operative day 4 or 5.

    Portal vein thrombosis is associated with higher tissue volume infused into the portal vein and higher portal pressures and is assessed using abdominal ultrasound.

  2. Clavien-Dindo classification of surgical complications

    Time frame: Within 30 days of surgery

    Grades surgical complications based on the level of treatment necessary to treat the complication.

  3. Mixed Meal Tolerance Test

    Time frame: 1 year

    Patient is given Boost HP (6cc/kg), ingested 5 minutes after t=0 blood draw. Blood is drawn every half hour for 2 hours.

  4. Intravenous Glucose tolerance test

    Time frame: 1 year

    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

  5. Glucose potentiated arginine stimulation

    Time frame: 1 year

    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.

  6. Hypoglycemic clamp

    Time frame: 1 year

    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

  7. Continuous glucose monitoring

    Time frame: 1 year

    3 days of CGM monitoring at one year will be obtained for mean glucose,standard deviation, and percent of time in hypo- and hyperglycemia

  8. Hemoglobin A1c levels

    Time frame: 1 year

    Measure of average glucose levels over last several weeks

  9. Insulin Use

    Time frame: 1 year

    calculated as units/kg/day, will be assessed from glucose and insulin diaries maintained by patients for 14 days, overlapping with day 90

  10. Hypoglycemic episodes

    Time frame: 1 year

    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.

  11. Clarke score

    Time frame: 1 year

    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

Sponsors and collaborators

Lead sponsor

University of Minnesota

Other

Registry information

Official study title

A Randomized Trial of Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis

Acronym: iSite

Important dates

Study start
2019
Primary completion
2024
Study completion
2024
First posted
Dec 19, 2018
Registry last updated
Jan 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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