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CompletedNCT00768651Updated Jun 18, 2015Results posted

Incretin Effect and Use After Clinical Islet Transplantation

A Phase 2 interventional study of Pantoprazole and Sitagliptin in Type 1 Diabetes, sponsored by University of Alberta. Completed at 1 site in Canada. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2015-06-18.

Sponsored by University of Alberta · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
8
Allocation
Not applicable
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Type 1 Diabetes
03

In context

Diabetes Mellitus, Type 1

3,614 studies on the registry are indexed under Diabetes Mellitus, Type 1; 586 are open to participants now.

This study's enrollment of 8 is below the median of 40 across 2,718 interventional studies indexed under Diabetes Mellitus, Type 1.

Browse Diabetes Mellitus, Type 1 studies →

Lead sponsor

University of Alberta is the lead sponsor of 819 studies on the registry; 168 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 3 (60%) have results posted.

Browse University of Alberta studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
8 participants (actual)

Study arms

  • 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 · Drug: Sitagliptin

Interventions

  • DrugPantoprazole

    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.

    Also known as: Pantoloc

  • DrugSitagliptin

    Starting on Day 1, Sitagliptin 100mg once daily administered orally at the same time each day for a period of 6 months.

    Also known as: Januvia

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 6 months

  2. Number of Participants Not Using Insulin for at Least One Week After 6 Months of Therapy

    Time frame: 6 months

  3. 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.

    Time frame: 6 months

  4. Number of Participants With Fasting Plasma Glucose (FPG) < 7 mmol/l After 6 Months of Therapy

    Time frame: 6 months

  5. 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.

    Time frame: 6 months

  6. 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.

    Time frame: Baseline and One month

  7. Change From Baseline on Gastrin Level After One Month of Therapy

    Gastrin levels were measured at baseline and at one month by method (manufacturer).

    Time frame: Baseline and One month

  8. HbA1c Plasma Laboratory Value for Participants After 6 Months of Therapy

    HbA1c was measured at baseline, 3, 6, and 9 months using method (manufacturer.

    Time frame: 6 months

  9. 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.

    Time frame: 6 months

  10. 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.

    Time frame: 6 months

  11. 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.

    Time frame: 6 months

  12. 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.

    Time frame: 6 months

  13. Blood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy

    Time frame: 6 months

  14. Weight Change From Baseline After 6 Months of Therapy

    Measuring the weight change from baseline at months: 1, 3, 6 and 9.

    Time frame: 6 months

Secondary outcomes

  1. 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).

    Time frame: After the 3 month washout period

  2. Insulin Dose (U/Day)

    Time frame: After the 3 month washout period

  3. 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.

    Time frame: 3 months - washout period

  4. 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.

    Time frame: After the 3 month washout period

  5. 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

    Time frame: After the 3 month washout period

  6. 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.

    Time frame: 3 months - washout period

  7. 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.

    Time frame: 3 months - washout period

  8. 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.

    Time frame: After the 3 month washout period

07

Results

Posted Jun 18, 2015
Limitations and caveats
The major weaknesses of the study are the small sample size and the lack of a control group.

Participant flow

Recruitment period took place between March 2010 thru October 2010. Consent took place in the Clinical Islet Transplant Program at the University of Alberta.

Participant flow — Overall Study
MilestoneSitagliptin + Pantoprazole
Started8
Completed7
Not completed1
Withdrew: Withdrawal by subject1

Outcome measures

PrimaryThe 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).

Time frame:
6 months
Reported as:
Number · proportion of participants
The Primary Endpoint Will be Insulin Independence After 6 Months of Therapy.
proportion of participantsOne Arm: Sitagliptin + Pantoprazole
The Primary Endpoint Will be Insulin Independence After 6 Months of Therapy.0.25 (-0.06 to 0.56)
Statistical analysis
  • One Arm: Sitagliptin + Pantoprazole · t-test, 2 sided · p = < 0.05
SecondaryInsulin 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).

Time frame:
After the 3 month washout period
Reported as:
Number · % of insulin indipendent participants
Insulin Independence After the 3 Month Washout Period
% of insulin indipendent participantsOne Arm: Sitagliptin + Pantoprazole
Insulin Independence After the 3 Month Washout Period0
SecondaryInsulin Dose (U/Day)
Time frame:
After the 3 month washout period

Results for this outcome have not been posted.

PrimaryNumber of Participants Not Using Insulin for at Least One Week After 6 Months of Therapy
Time frame:
6 months

Results for this outcome have not been posted.

PrimaryNumber of Participants With HbA1c < 6.0 % After 6 Months of Therapy

HbA1c was measured using method (manufacturer) at baseline, 3, 6 and 9 months.

Time frame:
6 months

Results for this outcome have not been posted.

PrimaryNumber of Participants With Fasting Plasma Glucose (FPG) < 7 mmol/l After 6 Months of Therapy
Time frame:
6 months

Results for this outcome have not been posted.

PrimaryMean 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.

Time frame:
6 months

Results for this outcome have not been posted.

PrimaryChange 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.

Time frame:
Baseline and One month

Results for this outcome have not been posted.

PrimaryChange From Baseline on Gastrin Level After One Month of Therapy

Gastrin levels were measured at baseline and at one month by method (manufacturer).

Time frame:
Baseline and One month

Results for this outcome have not been posted.

PrimaryHbA1c Plasma Laboratory Value for Participants After 6 Months of Therapy

HbA1c was measured at baseline, 3, 6, and 9 months using method (manufacturer.

Time frame:
6 months

Results for this outcome have not been posted.

PrimaryAcute 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.

Time frame:
6 months

Results for this outcome have not been posted.

PrimaryC-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.

Time frame:
6 months

Results for this outcome have not been posted.

PrimaryC-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.

Time frame:
6 months

Results for this outcome have not been posted.

PrimaryGlucose 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.

Time frame:
6 months

Results for this outcome have not been posted.

PrimaryBlood Glucose Laboratory Value Before Mixed Meal Tolerance Test (MMTT) After 6 Months of Therapy
Time frame:
6 months

Results for this outcome have not been posted.

PrimaryWeight Change From Baseline After 6 Months of Therapy

Measuring the weight change from baseline at months: 1, 3, 6 and 9.

Time frame:
6 months

Results for this outcome have not been posted.

SecondaryAcute 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.

Time frame:
3 months - washout period

Results for this outcome have not been posted.

SecondaryHbA1c 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.

Time frame:
After the 3 month washout period

Results for this outcome have not been posted.

SecondaryC-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

Time frame:
After the 3 month washout period

Results for this outcome have not been posted.

SecondaryC-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.

Time frame:
3 months - washout period

Results for this outcome have not been posted.

SecondaryGlucose 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.

Time frame:
3 months - washout period

Results for this outcome have not been posted.

SecondaryBlood 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.

Time frame:
After the 3 month washout period

Results for this outcome have not been posted.

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
One Arm: Sitagliptin + Pantoprazole—0/8 (0%)2/8 (25%)
Most frequent other events
Most frequent other events
EventOne Arm: Sitagliptin + Pantoprazole
Nausea or DiarrheaGastrointestinal disorders2/8

Baseline characteristics

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.

Age, Continuous
Age, Continuous(years)One Arm: Sitagliptin + Pantoprazole
Median54 (40 to 64)
Sex: Female, Male
Sex: Female, Male(Participants)One Arm: Sitagliptin + Pantoprazole
Female1
Male7
Region of Enrollment
Region of Enrollment(participants)One Arm: Sitagliptin + Pantoprazole
Canada8
Weight
Weight(kg)One Arm: Sitagliptin + Pantoprazole
Mean69 ± 15
BMI
BMI(kg/m^2)One Arm: Sitagliptin + Pantoprazole
Mean22.6 ± 3.4
Diabetes Duration Prior to 1st Transplant
Diabetes Duration Prior to 1st Transplant(years)One Arm: Sitagliptin + Pantoprazole
Mean36.1 (24.7 to 50.2)
Number of islet infusions
Number of islet infusions(number of islet infusions)One Arm: Sitagliptin + Pantoprazole
Median2 (1 to 4)
Islet equivalents infused
Islet equivalents infused(equivalents total)One Arm: Sitagliptin + Pantoprazole
Mean814,061 ± 231,463

6 further baseline measures are reported on the registry.

08

Study locations

1 site
  • University of Alberta - Clinical Islet Transplant Program
    Edmonton, Alberta T6G2C8, Canada
09

References and documents

Publications

  • 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. PubMed 27087519 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 18, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00768651
Lead sponsor
University of Alberta
Collaborators
Juvenile Diabetes Research Foundation
Responsible party
Sponsor
First posted
Oct 8, 2008
Start date
Oct 2008
Primary completion
Jul 2011
Completion
Dec 2011
Results posted
Jun 18, 2015
Last update
Jun 18, 2015

Study contacts

Peter Senior, MD, PhD
principal investigator · University of Alberta

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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