Incretin Effect and Use After Clinical Islet Transplantation
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Intervention: Pantoprazole; Sitagliptin
Intervention description: Starting on Day 1, Pantoprazole 80 mg daily (40 mg every morning and 40 mg every evening) administered orally at the same time each day for a period of 6 months.; Starting on Day 1, Sitagliptin 100mg once daily administered orally at the same time each day for a period of 6 months.
Intervention MeSH terms: Sitagliptin Phosphate; Pantoprazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      We aim to study if the administration of medications to increase the secretion of hormones
      from the intestines can improve glycemic control, reduce insulin use and promote β-cell
      regeneration/expansion in subjects with type 1 diabetes following islet transplantation who
      are back using small doses of insulin because of early graft dysfunction. We believe that the
      results will enable us to understand whether these drugs could be useful in islet transplant
      recipients, particularly if glycemic control deteriorates.
    

Eligibility criteria:

        Inclusion Criteria

        Subjects must meet the following criteria to be enrolled in this study:

          1. Male or female, aged 18 to 70, inclusive, who is a previous islet transplant recipient
             (at least 3 months since last islet transplant) and who received their transplant at
             the University of Alberta.

          2. Insulin independent for 3 months or longer after islet transplant.

          3. Early graft dysfunction as defined by:

               1. HbA1c >6% (but less than 7.5%); or

               2. fasting glucose > 7 mmol/L (126 mg/dl); or

               3. random glucose > 10 mmol/L (180 mg/dl), and

               4. Total insulin use of < 10 units/day.

          4. C-peptide positive.

          5. Able to provide informed consent.

        Exclusion Criteria:

        Subjects who meet any of the following criteria will be excluded from the study:

          1. Unable to provide informed consent.

          2. Prior therapy with sitagliptin or a proton pump inhibitor in the preceding 2 months.

          3. Vulnerable populations (i.e. cognitively impaired, pregnant women, residing in
             institutions, University of Alberta students or employees under the supervision of any
             of the investigators).

          4. Children, adolescent or patients with a "contraindication" or "warning" listed in the
             package insert of any of the study drugs:

               1. Hypersensitivity to sitagliptin or pantoprazole for any component of the
                  formulation.

               2. Renal disease or renal dysfunction (as suggested by serum creatinine levels ≥ 136
                  µmol/L (males), ≥ 124 µmol/L (females) or abnormal creatinine clearance; or
                  estimated by Glomerular Filtration Rate (GFR) <50 ml/min/1.73m2).

               3. Acute or chronic metabolic acidosis with or without coma (including diabetic
                  ketoacidosis).

          5. Uncontrolled hyperglycemia

          6. Any subject that in the opinion of the investigator would not be a good candidate for
             study participation.