Clinical trial NCT00768651: Incretin Effect and Use After Clinical Islet Transplantation
Official title: Pilot Study of Safety and Efficacy of Combined Use of Dipeptidyl-peptidase Inhibitor (Sitagliptin) and Proton Pump Inhibitor (Pantoprazole) to Prevent Beta-cell Apoptosis and Promote Islet Regeneration in Islet Transplant Recipients With Early Graft Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2008-10-08
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: This is a single centre non-randomized pilot study. Subjects will be recruited from the current cohort of islet transplant recipients at the University of Alberta.

The primary objective of the study is to evaluate whether the combination of sitagliptin and pantoprazole can restore insulin independence in previously insulin independent islet transplant recipients experiencing early graft dysfunction. The study will also evaluate the safety of the combination drug therapy.

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.

Primary outcomes:
measure: The Primary Endpoint Will be Insulin Independence After 6 Months of Therapy.
timeFrame: 6 months
measure: Number of Participants Not Using Insulin for at Least One Week After 6 Months of Therapy
timeFrame: 6 months
measure: Number of Participants With HbA1c < 6.0 % After 6 Months of Therapy
timeFrame: 6 months
measure: Number of Participants With Fasting Plasma Glucose (FPG) < 7 mmol/l After 6 Months of Therapy
timeFrame: 6 months
measure: Mean Daily Insulin Use (U/Day) After 6 Months of Therapy
timeFrame: 6 months
measure: Change From Baseline of GLP-1 Level After One Month of Therapy
timeFrame: Baseline and One month
measure: Change From Baseline on Gastrin Level After One Month of Therapy
timeFrame: Baseline and One month
measure: HbA1c Plasma Laboratory Value for Participants After 6 Months of Therapy
timeFrame: 6 months
measure: Acute Insulin Responses to Arginine After 6 Months of Therapy
timeFrame: 6 months
measure: C-peptide Laboratory Value at 90 Minutes After a Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy
timeFrame: 6 months
measure: C-peptide Laboratory Value Before a Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy
timeFrame: 6 months
measure: Glucose Laboratory Value at 90 Minutes After Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy.
timeFrame: 6 months
measure: Blood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy
timeFrame: 6 months
measure: Weight Change From Baseline After 6 Months of Therapy
timeFrame: 6 months
Secondary outcomes:
measure: Insulin Independence After the 3 Month Washout Period
timeFrame: After the 3 month washout period
measure: Insulin Dose (U/Day)
timeFrame: After the 3 month washout period
measure: Acute Insulin Response to Arginine After the 3 Month Washout Period
timeFrame: 3 months - washout period
measure: HbA1c Plasma Laboratory Value for Participants After the 3 Month Washout Period
timeFrame: After the 3 month washout period
measure: C-peptide Plasma Laboratory Value at 90 Minutes After a Mixed Meal Tolerance Test (MMTT) at the End of the 3 Month Washout Period.
timeFrame: After the 3 month washout period
measure: C-peptide Laboratory Value Before a Mixed Meal Tolerance Test (MMTT) After the 3 Month Washout Period.
timeFrame: 3 months - washout period
measure: Glucose Laboratory Value at 90 Minutes After Mixed Meal Tolerance Test (MMTT) After the 3 Month Washout Period.
timeFrame: 3 months - washout period
measure: Blood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) After the 3 Month Washout Period
timeFrame: After the 3 month washout period
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta - Clinical Islet Transplant Program
state: Alberta
Study officials:
affiliation: University of Alberta
name: Peter Senior, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Senior PA, Koh A, Yau J, Imes S, Dinyari P, Malcolm AJ, Light P, Shapiro AM. Sitagliptin plus pantoprazole can restore but not maintain insulin independence after clinical islet transplantation: results of a pilot study. Diabet Med. 2017 Feb;34(2):204-212. doi: 10.1111/dme.13131. Epub 2016 May 22.