The Prospective Evaluation of Pancreatic Function in Pancreas Transplant Recipients

The purpose of this study is to understand how the pancreas functions after transplantation and particularly why high blood sugar levels develop. It will also analyze the effect of the medicines used to prevent rejection on blood sugar levels.

The hypothesis to be tested is that hyperglycemia more than six months after successful pancreas transplant results from a defect in insulin secretion, insulin resistance, or both.

Study Overview

• Status: Completed
• Conditions: Diabetes; Transplant
• Intervention / Treatment: Procedure: Oral glucose tolerance test; Procedure: IV Glucose Tolerance Test

Detailed Description

Type I diabetes mellitus (DM1) is an autoimmune disease characterized by destruction of the insulin-secreting beta cells. Insulin replacement has been the cornerstone of therapy for patients with DM1. However, pancreas transplantation, utilizing the whole pancreas as a means to replace the destroyed beta cells, has become a therapeutic alternative. The goal of pancreas transplantation is the establishment of long-term euglycemia, thereby preventing or allowing for the repair of end-organ complications.

Maintenance of the pancreas allograft over many years remains the goal in following pancreas transplant recipients over time. The onset of hyperglycemia less than one year after transplant is usually due to issues of surgical technique or acute rejection. However, the onset of hyperglycemia after one year of pancreas transplant is more problematic because the underlying causes are less clear and have been less well characterized. Currently, there is no protocol for definitively identifying the causes of hyperglycemia in pancreas transplant recipients over one year. This project will systematically characterize beta cell function and peripheral tissue response to insulin in patients who have received an earlier successful pancreas transplant who have developed hyperglycemia.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University Of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Hyperglycemic pancreas transplant recipients:

  • ages 19-65
  • received a pancreas transplant ≥ 9 months previously
  • fasting glucose levels ≥ 126 mg/dl
  • hemoglobin A1C > 1% above normal

• Euglycemic pancreas transplant recipients:

  • ages 19-65
  • received a pancreas transplant ≥ 9 months previously
  • fasting glucose levels are < 126 mg/dl
  • normal HbA1C without taking any medications for the treatment of high blood sugars.

• Euglycemic Kidney Transplant Recipients:

  • ages 19-65
  • no prior diagnosis of diabetes
  • received a kidney transplant ≥ 9 months previously
  • showing continued function

• Euglycemic Healthy Control Subjects:

  • ages 19-65
  • no diabetes or renal disease

Exclusion Criteria:

• Hyperglycemic pancreas transplant recipients:

  • chronic illnesses that would decrease insulin sensitivity (
  • terminal illness
  • BMI > 30 kg/m2
  • serum creatinine > 2 mg/dl
  • hemoglobin < 10 g/dl
  • an episode of acute rejection with the preceding 3 months of entry.

• Euglycemic pancreas transplant recipients:

  • Exclusion criteria are the same as with hyperglycemic transplant patients.
  • no diagnosis of type 2 diabetes.

• Euglycemic Kidney Transplant Recipients:

  • Exclusion criteria are the same as for euglycemic pancreas transplant recipients above.

• Euglycemic Healthy Control Subjects:

  • chronic illnesses
  • medications known to affect glucose metabolism
  • a history of smoking
  • serum creatinine ≥ 1.5 mg/dl
  • BMI > 30 kg/m2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Euglycemic pancreas transplant recipients; Participants receiving a pancreas transplant who have blood glucose level is within the normal range	Procedure: Oral glucose tolerance test; test done over 2 hours; Procedure: IV Glucose Tolerance Test; Done over 4 hours
Active Comparator: Hyperglycemic pancreas transplant recipients; Participants receiving a pancreas transplant who have high blood glucose (blood sugar)	Procedure: Oral glucose tolerance test; test done over 2 hours; Procedure: IV Glucose Tolerance Test; Done over 4 hours
Active Comparator: Euglycemic Kidney Transplant Recipients; Participants receiving a kidney transplant who have blood glucose level is within the normal range	Procedure: Oral glucose tolerance test; test done over 2 hours; Procedure: IV Glucose Tolerance Test; Done over 4 hours
Active Comparator: Euglycemic Healthy Control Participants; Participants who do not receive either a pancreas or kidney transplant who have blood glucose level is within the normal range	Procedure: Oral glucose tolerance test; test done over 2 hours; Procedure: IV Glucose Tolerance Test; Done over 4 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate beta cell secretion	Evaluate beta cell secretion by oral glucose tolerance test (done over 2 hours) and IV Glucose Tolerance Test (done over 4 hours)	9 months post-transplant or at time of participation for controls
Evaluate insulin sensitivity/glucose effectiveness	Evaluate insulin sensitivity/glucose effectiveness by oral glucose tolerance test (done over 2 hours) and IV Glucose Tolerance Test (done over 4 hours)	9 months post-transplant or at time of participation for controls

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: James T Lane, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2000
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: December 11, 2007
• First Submitted That Met QC Criteria: December 11, 2007
• First Posted (Estimated): December 12, 2007

Study Record Updates

• Last Update Posted (Actual): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: transplant; pancreas; kidney; euglycemic; hyperglycemic
• Other Study ID Numbers: 0114-00-FB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No