Sitagliptin Therapy to Improve Outcomes After Islet Autotransplant

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Pancreatitis, Diabetes

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sitagliptin<br> | Drug: Sitagliptin<br>* 100 mg PO daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatitis, Pancreatectomy, Islet autotransplant, Sitagliptin, Diabetes