Treatment of Diabetes After Gastric Bypass With Sitagliptin

Study Overview
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Brief Summary
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The purpose of this study is to assess whether Januvia (sitagliptin phosphate 100mg) is safe and effective for the treatment of Type 2 Diabetes in patients who have had Gastric Bypass.

Detailed Description
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Januvia (sitagliptin phosphate 100mg) is an FDA approved medication for the treatment of Type 2 Diabetes. Sitagliptin works by inhibiting the Dipeptidyl peptidase-4 enzyme, resulting in increased active glucagon-like peptide-1 (GLP-1) levels. GLP-1 is an incretin which increases post-prandial insulin secretion. Because Gastric Bypass has also been shown to increase GLP-1 levels, this study seeks to determine the additional effect of DDP-4 inhibition on glucose control in patients who have elevated incretin levels post Gastric Bypass. The study will also assess if Januvia (Sitagliptin phosphate) is safe and well tolerated in patients after Gastric Bypass. Recruitment and data collection for this study was started at St. Luke's Hospital in New York, NY and later moved to Columbia University Medical Center in New York, NY.

Official Title
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A Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Assess Efficacy, Safety and Tolerability of Sitagliptin Phosphate 100 mg as Treatment for Recurrent, Persistent or Newly Diagnosed Type 2 Diabetes After Gastric Bypass

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin phosphate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be a resident of the NYC metropolitan area or be able to come for emergency unscheduled and regular weekly meetings in Manhattan. HbA1c ≥ 6.5% and ≤ 8.5 % or a fasting glucose ≥ 126 mg/dL or a random glucose ≥ 200 mg/dL at least 12 months after GBP surgery confirmed by central laboratory. Subject is capable and willing to give informed consent. Subject is otherwise in good general health, based on medical history and physical examination. Subject is a non smoker for at least 6 months prior to study start Female subjects of child bearing potential must use oral, injected or implanted hormonal methods of contraception from at least the commencement of their last normal period prior to the first administration of the challenge agent. Subjects using hormonal contraception should use a barrier method in addition from the first administration of challenge agent until their next normal period following the end of the study. Exclusion Criteria: History of type 1 diabetes Female subject is pregnant or breastfeeding. Recent (< 30 days) or simultaneous participation in another clinical trial. Any situation that can compromise the study, including serious illness or a predictable lack of cooperation from the subject.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sitagliptin phosphate<br>100 mg/day sitagliptin phosphate (Januvia) PO once a day for 4-5 weeks | Drug: Sitagliptin phosphate<br>* 100 mg/day orally<br>* Other names: Januvia;|
| Placebo Comparator: Placebo<br>1 Placebo pill / day PO once a day for 4-5 weeks | Other: Placebo<br>* 1 Placebo Pill per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Postprandial Glucose Levels After Mixed Meal Test | Glucose levels were measured in study participants while fasting and periodically over 3 hours after drinking a 200 kcal mixed meal test, before and after intervention (Sitagliptin or Placebo). | Baseline and  4 weeks | 
| Change in Area Under the Curve (AUC) Glucose Levels After Mixed Meal Test | Glucose levels were measured in study participants while fasting and periodically over 3 hours after drinking a 200 kcal mixed meal test, before and after intervention (Sitagliptin or Placebo). AUC was measured by trapezoidal method. | Baseline and  4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Satiety levels were measured in study participants while they were fasting and periodically over a three hour period after drinking a 200 kcal meal drink, before and after intervention via a Visual Analog Scale. Participants were asked to mark on a 0 to 150 millimeter scale their response to the following question: How full do you feel right now? with lower scores indicating not full at all and higher scores indicating extremely full. | Baseline and  4 weeks | 
| Occurrence of Side Effects In Relation to Sitagliptin | Side effects to Sitagliptin or Placebo were measured in study participants via Sigstad score questionnaire, while fasting and periodically during a 3 hour period after drinking a 200 kcal meal drink, before and after intervention. The Sigstad scoring system is based on the participants report of the occurrence of 16 symptoms suggestive of the dumping syndrome. Each symptom is given a different score. For example, desire to sit down (+4), breathlessness (+3), dizziness (+2), nausea (+1), vomiting (-4) etc.The scale can range from -5 to 34. Scores greater than or equal to 7, after glucose intake, are considered diagnostic of dumping syndrome. | 6 weeks | 
| Active GLP-1 | Active GLP-1 (Fasting and during a Mixed Meal Test). The Change in Fasting Active GLP-1 refers to the change in fasting active GLP-1 from pre-intervention time point to post-intervention time point. The Change in Peak Active GLP-1 refers to the change in the peak active GLP-1 level from the pre-intervention time point to post-intervention time point. | Pre-Intervention and Post-Intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Januvia, Sitagliptin, Diabetes, Gastric-Bypass