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Type 1 DiabetesPhase 2NCT00768651

Incretin Effect and Use After Clinical Islet Transplantation

A Phase 2 study testing Pantoprazole and Sitagliptin in people with Type 1 Diabetes, run by University of Alberta at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Type 1 Diabetes
What is being tested?
Pantoprazole and Sitagliptin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteCanada
Study dates
Oct 2008to Dec 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • random glucose > 10 mmol/L (180 mg/dl), and
  • Total insulin use of < 10 units/day.
  • C-peptide positive.
  • Able to provide informed consent.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • University of Alberta - Clinical Islet Transplant Program

    Edmonton, Alberta, T6G2C8

Other trials in Canada

About this study

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

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.

Conditions
Type 1 Diabetes
Being tested
Pantoprazole, Sitagliptin
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PantoprazoleDrug

    Also called Pantoloc

    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.

  • SitagliptinDrug

    Also called Januvia

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

Study groups in NCT00768651
Study groupRoleWhat they receive
One arm: Sitagliptin + PantoprazoleExperimentalIntervention Details: Sitagliptin 100 mg daily and Pantoprazole 40 mg bid for 6 months, followed by a three-month washout.
Receives: Drug: Pantoprazole; Drug: Sitagliptin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 6 months

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

    Measured: 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.

    Measured: 6 months

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

    Measured: 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.

    Measured: 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.

    Measured: 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).

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 6 months

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

    Measured: 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.

    Measured: 6 months

Secondary outcomes (8)
  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).

    Measured: After the 3 month washout period

  2. Insulin Dose (U/Day)

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: After the 3 month washout period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2008 (estimated)
  2. Study startOct 2008
  3. Primary completionJul 2011
  4. Study completionDec 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00768651
Sponsor's protocol ID
7331
Status last verified
May 2015
First submitted
7 Oct 2008
Last updated
18 Jun 2015
Data monitoring committee
No

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pantoprazole and Sitagliptin in people with Type 1 Diabetes, run by University of Alberta at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Primary Endpoint Will be Insulin Independence After 6 Months of Therapy. (time frame: 6 months). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00768651, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2015.

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