Incretin Effect and Use After Clinical Islet Transplantation - Full Text View

Sponsor:	University of Alberta
Information provided by:	University of Alberta
ClinicalTrials.gov Identifier:	NCT00768651

Purpose

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.

Condition	Intervention	Phase
Type 1 Diabetes	Drug: Pantoprazole Drug: Sitagliptin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy 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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 1 Islet Cell Transplantation

Drug Information available for: Pantoprazole Pantoprazole Sodium Sitagliptin Sitagliptin phosphate

U.S. FDA Resources

Further study details as provided by University of Alberta:

Primary Outcome Measures:

The primary endpoint will be insulin independence after 6 months of therapy. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Insulin independence after the 3 month washout period; insulin and C-peptide responses to the intravenous arginine and mixed meal tests; reduction in insulin use; and improvement in glycemic control as determined by HbA1c and CGMS. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	8
Study Start Date:	October 2008
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Intervention Details:

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.

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

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 off 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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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:
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.
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:
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 GFR <50 ml/min/1.73m2).
3. 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768651

Contacts

Contact: Peter Senior, MD, PhD

780-407-8852

petersenior@ualberta.ca

Locations

Canada, Alberta
University of Alberta - Clinical Islet Transplant Program	Recruiting
Edmonton, Alberta, Canada, T6G2C8
Contact: Janet Wright 780 407 8348 janet.wright@ualberta.ca
Principal Investigator: Peter Senior, MD, PhD

Sponsors and Collaborators

University of Alberta

Investigators

Principal Investigator:

Peter Senior, MD, PhD

University of Alberta

More Information

No publications provided

Responsible Party:	University of Alberta ( Peter Senior, MD, PhD )
Study ID Numbers:	7331
Study First Received:	October 7, 2008
Last Updated:	January 26, 2010
ClinicalTrials.gov Identifier:	NCT00768651 History of Changes
Health Authority:	Canada: Health Canada

Additional relevant MeSH terms:

Metabolic Diseases
Autoimmune Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Pantoprazole
Diabetes Mellitus
Gastrointestinal Agents
Endocrine System Diseases
Enzyme Inhibitors

Pharmacologic Actions
Protease Inhibitors
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Diabetes Mellitus, Type 1
Proton Pump Inhibitors
Therapeutic Uses
Anti-Ulcer Agents
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on February 08, 2010