Incretin Effect and Use After Clinical Islet Transplantation
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ClinicalTrials.gov Identifier: NCT00768651 |
Recruitment Status
:
Completed
First Posted
: October 8, 2008
Results First Posted
: June 18, 2015
Last Update Posted
: June 18, 2015
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Type 1 Diabetes | Drug: Pantoprazole Drug: Sitagliptin | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 8 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 Start Date : | October 2008 |
Actual Primary Completion Date : | July 2011 |
Actual Study Completion Date : | December 2011 |

Arm | Intervention/treatment |
---|---|
Experimental: One arm: Sitagliptin + Pantoprazole
Intervention Details: Sitagliptin 100 mg daily and Pantoprazole 40 mg bid for 6 months, followed by a three-month washout. |
Drug: Pantoprazole
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.
Other Name: Pantoloc
Drug: Sitagliptin
Starting on Day 1, Sitagliptin 100mg once daily administered orally at the same time each day for a period of 6 months.
Other Name: Januvia
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- The Primary Endpoint Will be Insulin Independence After 6 Months of Therapy. [ Time Frame: 6 months ]Insulin independence was defined as no insulin use for at least one week, HbA1c < 6.0%, fasting plasma glucose < 7.0 mmol/l, fasting or stimulated c-peptide ≥ 0.5 ng/ml. In addition capillary blood glucose levels could not be >7.8 mmol/l (fasting) or > 10 mmol/l (post-prandial) on more than three occasions in the preceding week. Mean daily insulin use was calculated from the three days prior to study visits. Blinded continuous glucose monitoring (CGM) was performed using the iPro device and Carelink software (Medtronic, Mississauga, ON, CA).
- Number of Participants Not Using Insulin for at Least One Week After 6 Months of Therapy [ Time Frame: 6 months ]
- Number of Participants With HbA1c < 6.0 % After 6 Months of Therapy [ Time Frame: 6 months ]HbA1c was measured using method (manufacturer) at baseline, 3, 6 and 9 months.
- Number of Participants With Fasting Plasma Glucose (FPG) < 7 mmol/l After 6 Months of Therapy [ Time Frame: 6 months ]
- Mean Daily Insulin Use (U/Day) After 6 Months of Therapy [ Time Frame: 6 months ]Mean daily insulin use was calculated from the three days prior to study visits and performed at baseline, 3, 6, and 9 months.
- Change From Baseline of GLP-1 Level After One Month of Therapy [ Time Frame: Baseline and One month ]Fasting Glucagon-Like Peptide (GLP-1) levels were measured at baseline and one month. Blood samples were collected in p700 vacutainers (Becton Dickinson, Franklin Lakes, NJ) containing a Dipeptidyl peptidase-4 (DPP4) protease inhibitor cocktail to measure total and active GLP-1 in duplicate using a commercially available ELISA (kit manufacturer) and expressed as the ratio of active:total GLP-1.
- Change From Baseline on Gastrin Level After One Month of Therapy [ Time Frame: Baseline and One month ]Gastrin levels were measured at baseline and at one month by method (manufacturer).
- HbA1c Plasma Laboratory Value for Participants After 6 Months of Therapy [ Time Frame: 6 months ]HbA1c was measured at baseline, 3, 6, and 9 months using method (manufacturer.
- Acute Insulin Responses to Arginine After 6 Months of Therapy [ Time Frame: 6 months ]An intravenous arginine stimulation test (AST) [Ryan:2002cg] was performed at baseline, 6, and 9 months to assess Graft function.
- C-peptide Laboratory Value at 90 Minutes After a Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy [ Time Frame: 6 months ]Measuring of C-peptide before and 90 minutes after a mixed meal tolerance test (MMTT) [Ryan:2005ts] at baseline, 6 and 9 months to assess Graft function.
- C-peptide Laboratory Value Before a Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy [ Time Frame: 6 months ]Measuring of C-peptide before and 90 minutes after a mixed meal tolerance test (MMTT) [Ryan:2005ts] at baseline, 6 and 9 months to assess Graft function.
- Glucose Laboratory Value at 90 Minutes After Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy. [ Time Frame: 6 months ]Measuring Glucose before and 90 minutes after Mixed Meal Tolerance Test (MMTT) [Ryan: 2005ts] at baseline, 6 and 9 months to assess Graft function.
- Blood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy [ Time Frame: 6 months ]
- Weight Change From Baseline After 6 Months of Therapy [ Time Frame: 6 months ]Measuring the weight change from baseline at months: 1, 3, 6 and 9.
- Insulin Independence After the 3 Month Washout Period [ Time Frame: After the 3 month washout period ]Insulin independence was defined as no insulin use for at least one week, HbA1c < 6.0%, fasting plasma glucose < 7.0 mmol/l, fasting or stimulated c-peptide ≥ 0.5 ng/ml. In addition capillary blood glucose levels could not be >7.8 mmol/l (fasting) or > 10 mmol/l (post-prandial) on more than three occasions in the preceding week. Mean daily insulin use was calculated from the three days prior to study visits. Blinded continuous glucose monitoring (CGM) was performed using the iPro device and Carelink software (Medtronic, Mississauga, ON, CA).
- Insulin Dose (U/Day) [ Time Frame: After the 3 month washout period ]
- Acute Insulin Response to Arginine After the 3 Month Washout Period [ Time Frame: 3 months - washout period ]An intravenous Arginine stimulation test (AST) [Ryan:2002cg] was performed at baseline, 6, and 9 months to assess Graft function. The Arginine is a proxy for insulin secretory reserve (Robertson:2004br)(Rickels:2007cg) and correlates with islet mass in the context of islet allo-transplant (Ryan:2002cg), auto-transplant (Teuscher:1998eu) and hemipancreatectomy (Seaquist:1992iv). An increase in Arginine (AIRarg) would have suggested an increase in beta cell mass.
- HbA1c Plasma Laboratory Value for Participants After the 3 Month Washout Period [ Time Frame: After the 3 month washout period ]Measuring of HbA1c using method (manufacturer) at baseline, and months: 1, 3, 6, 9.
- C-peptide Plasma Laboratory Value at 90 Minutes After a Mixed Meal Tolerance Test (MMTT) at the End of the 3 Month Washout Period. [ Time Frame: After the 3 month washout period ]Measuring of C-peptide before and 90 minutes after a Mixed Meal Tolerance Test (MMTT) [Ryan:2005ts] at baseline, 6 and 9 months to assess Graft function. Ther
- C-peptide Laboratory Value Before a Mixed Meal Tolerance Test (MMTT) After the 3 Month Washout Period. [ Time Frame: 3 months - washout period ]Measuring of C-peptide before and 90 minutes after a mixed meal tolerance test (MMTT) [Ryan:2005ts] at baseline, 6 and 9 months to assess Graft function.
- Glucose Laboratory Value at 90 Minutes After Mixed Meal Tolerance Test (MMTT) After the 3 Month Washout Period. [ Time Frame: 3 months - washout period ]Measuring Blood Glucose before and 90 minutes after Mixed Meal Tolerance Test (MMTT) [Ryan: 2005ts] at baseline, 6 and 9 months to assess Graft function.
- Blood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) After the 3 Month Washout Period [ Time Frame: After the 3 month washout period ]Measuring Blood Glucose before and 90 minutes after Mixed Meal Tolerance Test (MMTT) [Ryan: 2005ts] at baseline, 6 and 9 months to assess Graft function.

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Ages Eligible for Study: | 18 Years to 70 Years (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
Subjects must meet the following criteria to be enrolled in this study:
- 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.
- Insulin independent for 3 months or longer after islet transplant.
-
Early graft dysfunction as defined by:
- HbA1c >6% (but less than 7.5%); or
- fasting glucose > 7 mmol/L (126 mg/dl); or
- random glucose > 10 mmol/L (180 mg/dl), and
- Total insulin use of < 10 units/day.
- C-peptide positive.
- Able to provide informed consent.
Exclusion Criteria:
Subjects who meet any of the following criteria will be excluded from the study:
- Unable to provide informed consent.
- Prior therapy with sitagliptin or a proton pump inhibitor in the preceding 2 months.
- 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).
-
Children, adolescent or patients with a "contraindication" or "warning" listed in the package insert of any of the study drugs:
- Hypersensitivity to sitagliptin or pantoprazole for any component of the formulation.
- 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).
- Acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis).
- Uncontrolled hyperglycemia
- Any subject that in the opinion of the investigator would not be a good candidate for study participation.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00768651
Canada, Alberta | |
University of Alberta - Clinical Islet Transplant Program | |
Edmonton, Alberta, Canada, T6G2C8 |
Principal Investigator: | Peter Senior, MD, PhD | University of Alberta |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | University of Alberta |
ClinicalTrials.gov Identifier: | NCT00768651 History of Changes |
Other Study ID Numbers: |
7331 |
First Posted: | October 8, 2008 Key Record Dates |
Results First Posted: | June 18, 2015 |
Last Update Posted: | June 18, 2015 |
Last Verified: | May 2015 |
Additional relevant MeSH terms:
Diabetes Mellitus, Type 1 Diabetes Mellitus Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases Sitagliptin Phosphate Pantoprazole Hypoglycemic Agents Physiological Effects of Drugs |
Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Dipeptidyl-Peptidase IV Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Ulcer Agents Gastrointestinal Agents Proton Pump Inhibitors |