Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Juvenile Diabetes Research Foundation | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| One arm: Sitagliptin + Pantoprazole | Experimental | Intervention Details: Sitagliptin 100 mg daily and Pantoprazole 40 mg bid for 6 months, followed by a three-month washout. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pantoprazole | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| The Primary Endpoint Will be Insulin Independence After 6 Months of Therapy. | 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). | 6 months |
| Number of Participants Not Using Insulin for at Least One Week After 6 Months of Therapy | 6 months | |
| Number of Participants With HbA1c < 6.0 % After 6 Months of Therapy | HbA1c was measured using method (manufacturer) at baseline, 3, 6 and 9 months. | 6 months |
| Number of Participants With Fasting Plasma Glucose (FPG) < 7 mmol/l After 6 Months of Therapy | 6 months | |
| Mean Daily Insulin Use (U/Day) After 6 Months of Therapy | Mean daily insulin use was calculated from the three days prior to study visits and performed at baseline, 3, 6, and 9 months. | 6 months |
| Change From Baseline of GLP-1 Level After One Month of Therapy | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Independence 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). |
Not provided
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:
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:
Uncontrolled hyperglycemia
Any subject that in the opinion of the investigator would not be a good candidate for study participation.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Peter Senior, MD, PhD | University of Alberta | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alberta - Clinical Islet Transplant Program | Edmonton | Alberta | T6G2C8 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27087519 | Derived | 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. |
Not provided
Not provided
Patients signed Informed Consent after a consultation with the PI. Then they proceeded through the evaluation phase of the study. During this phase, some patients were excluded based on the protocol's inclusion and exclusion criteria (i.e. lab reports or procedure that did not meet protocol standards).
Recruitment period took place between March 2010 thru October 2010. Consent took place in the Clinical Islet Transplant Program at the University of Alberta.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Sitagliptin + Pantoprazole | Intervention Details: 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, followed by a three-month washout. Sitagliptin: Starting on Day 1, Sitagliptin 100mg once daily administered orally at the same time each day for a period of 6 months, followed by a three-month washout. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Patients with evidence of early graft insufficiency following a period of insulin independence after one or more islet infusions for c-peptide negative type 1 diabetes participated in the study.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | One Arm: Sitagliptin + Pantoprazole | Intervention Details: Sitagliptin 100 mg daily and Pantoprazole 40 mg bid for 6 months, followed by a three-month washout: 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. Sitagliptin: Starting on Day 1, Sitagliptin 100mg once daily administered orally at the same time each day for a period of 6 months. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Primary Endpoint Will be Insulin Independence After 6 Months of Therapy. | 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). | Per Protocol Set of participants: The participants of subjects in full analysis set who were: compliant with the protocol, compliant with pre-specified exposure to the treatment regimen, and available for measurements of primary variables. | Posted | Number | 95% Confidence Interval | proportion of participants | 6 months |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | One Arm: Sitagliptin + Pantoprazole | Intervention Details: Sitagliptin 100 mg daily and Pantoprazole 40 mg bid for 6 months, followed by a three-month washout: 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. Sitagliptin: Starting on Day 1, Sitagliptin 100mg once daily administered orally at the same time each day for a period of 6 months. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea or Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
The major weaknesses of the study are the small sample size and the lack of a control group.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peter Senior, MD, PhD - Professor of Medicine, Medical Director-Clinical Islet Transplant Program, | Faculty of Medicine and Dentistry, University of Alberta | 780-407-1480 | peters@islet.ca |
Not provided
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077402 | Pantoprazole |
| D000068900 | Sitagliptin Phosphate |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Sitagliptin | Drug | Starting on Day 1, Sitagliptin 100mg once daily administered orally at the same time each day for a period of 6 months. |
|
|
| Baseline and One month |
| Change From Baseline on Gastrin Level After One Month of Therapy | Gastrin levels were measured at baseline and at one month by method (manufacturer). | Baseline and One month |
| HbA1c Plasma Laboratory Value for Participants After 6 Months of Therapy | HbA1c was measured at baseline, 3, 6, and 9 months using method (manufacturer. | 6 months |
| Acute Insulin Responses to Arginine After 6 Months of Therapy | An intravenous arginine stimulation test (AST) [Ryan:2002cg] was performed at baseline, 6, and 9 months to assess Graft function. | 6 months |
| C-peptide Laboratory Value at 90 Minutes After a Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy | 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. | 6 months |
| C-peptide Laboratory Value Before a Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy | 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. | 6 months |
| Glucose Laboratory Value at 90 Minutes After Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy. | Measuring Glucose before and 90 minutes after Mixed Meal Tolerance Test (MMTT) [Ryan: 2005ts] at baseline, 6 and 9 months to assess Graft function. | 6 months |
| Blood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy | 6 months |
| Weight Change From Baseline After 6 Months of Therapy | Measuring the weight change from baseline at months: 1, 3, 6 and 9. | 6 months |
| After the 3 month washout period |
| Insulin Dose (U/Day) | After the 3 month washout period |
| Acute Insulin Response to Arginine After the 3 Month 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. | 3 months - washout period |
| HbA1c Plasma Laboratory Value for Participants After the 3 Month Washout Period | Measuring of HbA1c using method (manufacturer) at baseline, and months: 1, 3, 6, 9. | After the 3 month washout period |
| C-peptide Plasma Laboratory Value at 90 Minutes After a Mixed Meal Tolerance Test (MMTT) at the End of 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 | After the 3 month washout period |
| C-peptide Laboratory Value Before a Mixed Meal Tolerance Test (MMTT) 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. | 3 months - washout period |
| Glucose Laboratory Value at 90 Minutes After Mixed Meal Tolerance Test (MMTT) 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. | 3 months - washout period |
| Blood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) 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. | After the 3 month washout period |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| Diabetes Duration Prior to 1st Transplant | Mean | Full Range | years |
|
| Number of islet infusions | Median | Full Range | number of islet infusions |
|
| Islet equivalents infused | Mean | Standard Deviation | equivalents total |
|
| Islet equivalents infused | Mean | Standard Deviation | equivalents per kg |
|
| Time since first transplant | Median | Full Range | months |
|
| Interval since last transplant | Median | Full Range | months |
|
| Time insulin free | Median | Full Range | months |
|
| Tacrolimus daily dose | Mean | Standard Deviation | mg |
|
| Mycophenolate daily dose | Mean | Standard Deviation | mg |
|
Intervention Details: Sitagliptin 100 mg daily and Pantoprazole 40 mg bid for 6 months, followed by a three-month washout: 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. Sitagliptin: Starting on Day 1, Sitagliptin 100mg once daily administered orally at the same time each day for a period of 6 months. |
|
|
|
| Secondary | Insulin Independence 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). | Per Protocol Set of participants; The subset of participants in full analysis set who were: compliant with the protocol, compliant with pre-specified exposure to the treatment regimen, and available for measurements of primary and secondary variables. | Posted | Number | % of insulin indipendent participants | After the 3 month washout period |
|
|
|
| Secondary | Insulin Dose (U/Day) | Not Posted | After the 3 month washout period |
| Primary | Number of Participants Not Using Insulin for at Least One Week After 6 Months of Therapy | Not Posted | 6 months |
| Primary | Number of Participants With HbA1c < 6.0 % After 6 Months of Therapy | HbA1c was measured using method (manufacturer) at baseline, 3, 6 and 9 months. | Not Posted | 6 months |
| Primary | Number of Participants With Fasting Plasma Glucose (FPG) < 7 mmol/l After 6 Months of Therapy | Not Posted | 6 months |
| Primary | Mean Daily Insulin Use (U/Day) After 6 Months of Therapy | Mean daily insulin use was calculated from the three days prior to study visits and performed at baseline, 3, 6, and 9 months. | Not Posted | 6 months |
| Primary | Change From Baseline of GLP-1 Level After One Month of Therapy | 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. | Not Posted | Baseline and One month |
| Primary | Change From Baseline on Gastrin Level After One Month of Therapy | Gastrin levels were measured at baseline and at one month by method (manufacturer). | Not Posted | Baseline and One month |
| Primary | HbA1c Plasma Laboratory Value for Participants After 6 Months of Therapy | HbA1c was measured at baseline, 3, 6, and 9 months using method (manufacturer. | Not Posted | 6 months |
| Primary | Acute Insulin Responses to Arginine After 6 Months of Therapy | An intravenous arginine stimulation test (AST) [Ryan:2002cg] was performed at baseline, 6, and 9 months to assess Graft function. | Not Posted | 6 months |
| Primary | C-peptide Laboratory Value at 90 Minutes After a Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy | 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. | Not Posted | 6 months |
| Primary | C-peptide Laboratory Value Before a Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy | 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. | Not Posted | 6 months |
| Primary | Glucose Laboratory Value at 90 Minutes After Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy. | Measuring Glucose before and 90 minutes after Mixed Meal Tolerance Test (MMTT) [Ryan: 2005ts] at baseline, 6 and 9 months to assess Graft function. | Not Posted | 6 months |
| Primary | Blood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy | Not Posted | 6 months |
| Primary | Weight Change From Baseline After 6 Months of Therapy | Measuring the weight change from baseline at months: 1, 3, 6 and 9. | Not Posted | 6 months |
| Secondary | Acute Insulin Response to Arginine After the 3 Month 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. | Not Posted | 3 months - washout period |
| Secondary | HbA1c Plasma Laboratory Value for Participants After the 3 Month Washout Period | Measuring of HbA1c using method (manufacturer) at baseline, and months: 1, 3, 6, 9. | Not Posted | After the 3 month washout period |
| Secondary | C-peptide Plasma Laboratory Value at 90 Minutes After a Mixed Meal Tolerance Test (MMTT) at the End of 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 | Not Posted | After the 3 month washout period |
| Secondary | C-peptide Laboratory Value Before a Mixed Meal Tolerance Test (MMTT) 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. | Not Posted | 3 months - washout period |
| Secondary | Glucose Laboratory Value at 90 Minutes After Mixed Meal Tolerance Test (MMTT) 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. | Not Posted | 3 months - washout period |
| Secondary | Blood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) 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. | Not Posted | After the 3 month washout period |
| 0 |
| 8 |
| 2 |
| 8 |
Not provided
Not provided
Not provided
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D011725 |
| Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D014230 | Triazoles |
| D001393 | Azoles |
| D011719 | Pyrazines |