Sitagliptin Therapy to Improve Outcomes After Islet Autotransplant

A Double-Blind, Randomized, Placebo Controlled Intervention Study to Assess the Impact of Sitagliptin 100 mg/Day for 1 Year on Insulin Independence Following Pancreatectomy and Autoislet Transplantation

The purpose of the study is to test the effects of sitagliptin on the need for insulin (the hormone that lowers blood sugars) by patients who receive a pancreatectomy and islet autotransplant for chronic pancreatitis.

Study Overview

• Status: Completed
• Conditions: Diabetes; Pancreatitis
• Intervention / Treatment: Drug: Placebo; Drug: Sitagliptin

Detailed Description

At the current time, about one-third of patients are insulin independent (do not need to take insulin) after autotransplant, but the other two-thirds still need some insulin. Sitagliptin works by increasing the amount of a hormone called glucagon-like peptide 1, or GLP-1, in the body which then increases the amount of insulin that is made by the beta cells(the insulin producing cell of the islets). GLP-1 might also help protect beta cells from dying under stressful conditions and increase the production of new beta cells.

The primary goal of this study is to see if taking sitagliptin for one year after islet autotransplant increases the number of patients who achieve and maintain insulin independence. Other goals of this study are to see if sitagliptin reduces the amount of insulin injections needed or helps the islets make more insulin.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years
• Scheduled for total pancreatectomy and IAT at UM

Exclusion Criteria:

• Pre-existing diabetes mellitus or hyperglycemia with fasting glucose ≥115 mg/dl
• Medical conditions which, in the opinion of the investigator, might impact islet function (e.g asthma or inflammatory disease requiring chronic systemic corticosteroids)
• Significant renal disease: serum creatinine levels of >3.0 mg/dL in men and >2.5 mg/dL in women, or end-stage renal disease requiring hemodialysis or peritoneal dialysis.
• For female subjects, plans to become pregnant or unwillingness to practice birth control for 18 months.
• Islet yield <1,000 IE/kg body weight (exclusion for treatment with drug/placebo)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Active Comparator: Sitagliptin	Drug: Sitagliptin; 100 mg PO daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Independence	percentage of patients insulin independent	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Independence	percentage of patients insulin independent	18 months
Area Under the Curve (AUC) C-peptide (ng/dL*Min)	AUC C-peptide obtained from a mixed meal test (measured time 0 to 2 hours after Boost HP)	12 months
AUC C-peptide	AUC C-peptide (ng/dL*min) from mixed meal tolerance test (measured times 0 to 2 hours after Boost HP)	18 months
Acute C-peptide Response (ACR) to Glucose	Derived from intravenous gluocose tolerance testing (0 to 10 minute measures after dextrose bolus)	12 months
Acute C-peptide Response (ACR) to Glucose	Derived from intravenous glucose tolerance test (0 to 10 minute measures after IV dextrose bolus)	18 months

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Melena Bellin, MD, University of Minnesota

Publications and helpful links

General Publications

• Harindhanavudhi T, Yang Y, Hodges JS, Pruett TL, Kirchner V, Beilman GJ, Bellin MD. Body Composition is Associated With Islet Function After Pancreatectomy and Islet Autotransplantation for Pancreatitis. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e496-e506. doi: 10.1210/clinem/dgaa790.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: August 4, 2010
• First Submitted That Met QC Criteria: August 20, 2010
• First Posted (Estimate): August 23, 2010

Study Record Updates

• Last Update Posted (Actual): May 31, 2017
• Last Update Submitted That Met QC Criteria: May 2, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Diabetes; Pancreatectomy; Sitagliptin; Pancreatitis; Islet autotransplant
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: 1006M83756

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO