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

Sponsored by:	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: Metformin hydrochloride Drug: Pantoprazole Drug: Sitagliptin	Phase II

MedlinePlus related topics: Diabetes Diabetes Type 1 Islet Cell Transplantation

Drug Information available for: Pantoprazole Pantoprazole Sodium Metformin Metformin hydrochloride Sitagliptin phosphate Sitagliptin Benzocaine

U.S. FDA Resources

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), Proton Pump Inhibitor (Pantoprazole) and Metformin to Prevent Beta-Cell Apoptosis and Promote Islet Regeneration in Islet Transplant Recipients With Early Graft Dysfunction

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:

500 mg twice daily, starting on day -1 before islet transplantation, with dose titration if necessary to minimize side effects.

Will be started at 40 mg twice daily orally approximately one month before islet transplant. Dose titration will be carried out at 20 mg increments (up to a maximum dose of 120 mg twice daily) if required to achieve and maintain serum gastrin levels >250 - 300 pg/ml if possible.

Will be started at 100 mg daily orally starting on day -1 before islet transplant and will continue for at least 1 year post-transplant.

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 objective is to study whether the combination of sitagliptin, pantoprazole and metformin can restore insulin independence in previously insulin independent islet transplant recipients experiencing early graft dysfunction.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects are required to meet the following inclusion criteria prior to enrollment:

Subjects must have evidence of early graft dysfunction as defined by:
1. Insulin independence with sub-optimal glycemic control as indicated by HbA1c >6% or fasting glucose > 7 mmol/L or random glucose > 10 mmol/L; or
2. Total insulin use of ≤ 10 units/day.
Subjects must have detectable C-peptide.
Subject must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent

Exclusion Criteria:

Insulin independence with sub-optimal glycemic control as indicated by HbA1c <6% or fasting glucose <7 mmol/L or random glucose <10 mmol/L; or
Total insulin use of ≥10 units/day.
Subjects must not have detectable C-peptide.

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

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

Study placed in the following topic categories:

Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Pantoprazole
Metformin
Benzocaine

Diabetes Mellitus
Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Sitagliptin

Additional relevant MeSH terms:

Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Therapeutic Uses
Anti-Ulcer Agents

Physiological Effects of Drugs
Gastrointestinal Agents
Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009