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Completed

NCT Number: NCT00768651

Incretin Effect and Use After Clinical Islet Transplantation

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.

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Key information

Conditions

Type 1 Diabetes Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alberta - Clinical Islet Transplant Program

Edmonton, Alberta, T6G2C8, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Other names: Pantoloc

Sitagliptin

Drug

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

Other names: Januvia

Primary outcomes

  1. 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).

  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

    Time frame: 6 months

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

    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.

  6. 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.

  7. 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).

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  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

    Time frame: 6 months

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

Secondary outcomes

  1. 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).

  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

    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.

  4. 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.

  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.

    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

  6. 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.

  7. 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.

  8. 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.

Sponsors and collaborators

Lead sponsor

University of Alberta

Other

Collaborators

  • Juvenile Diabetes Research Foundation

Registry information

Official study 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

Important dates

Study start
2008
Primary completion
2011
Study completion
2011
First posted
Oct 8, 2008
Registry last updated
Jun 18, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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