Incretin Effect and Use After Clinical Islet Transplantation

NCT ID: NCT00768651

Last Updated: 2015-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2011-12-31

Brief 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

One arm: Sitagliptin + Pantoprazole

Intervention Details:

Sitagliptin 100 mg daily and Pantoprazole 40 mg bid for 6 months, followed by a three-month washout.

Group Type: EXPERIMENTAL

Pantoprazole

Intervention Type: 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.

Sitagliptin

Intervention Type: DRUG

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

Interventions

Pantoprazole

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.

Intervention Type: DRUG

Sitagliptin

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

Intervention Type: DRUG

Other Intervention Names

Pantoloc; Januvia

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Senior, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

University of Alberta - Clinical Islet Transplant Program

Edmonton, Alberta, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 27087519 (View on PubMed)

Other Identifiers

7331

Identifier Type: -

Identifier Source: org_study_id