A Dose-response of the Effects of Exendin-9,39 on GI Symptoms and Food Intake

Study Overview
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Brief Summary
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Exendin-(9,39) has been shown to have effects on beta-cell function, and after gastric bypass, to accelerate gastrointestinal transit. - infused at rates of 300pmol/kg/min. Given that gastrointestinal transit is typically delayed by Glucagon-Like Peptide-1 (GLP-1) and also that this hormone causes decreased food intake through increased satiation, it is reasonable to expect an effect of Exendin-9,39 on appetite. This may help explain the effects of gastric bypass on food intake. To examine the effect of Exendin on food intake we propose a dose-response study to determine whether the compound has effects in a dose-dependent fashion. We will examine the presence of gastrointestinal symptoms as well as food intake in the immediate aftermath of a test meal and the subsequent hours.

Official Title
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A Dose-response Study of the Effects of Exendin-9,39 on Gastrointestinal Symptoms and Food Intake.

Conditions
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Obesity, Diabetes, Roux-en-Y Gastric Bypass

Intervention / Treatment
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* Drug: Exendin-9,39
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have undergone Roux en-Y Gastric Bypass at least 6 months prior to enrollment in the study. Subjects without active systemic illness. Exclusion Criteria: Subjects <20 years of age will not be studied to minimize the possibility of type 1 diabetes. Subjects >70 years of age will not be studied to minimize the potential confounding effects of age on glucose tolerance.

Ages Eligible for Study
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Minimum Age: 20 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br>a saline infusion will be started and maintained till the end of the study at 1300 (300 minutes). | Other: Saline<br> <br> |
| Active Comparator: Exendin-9,39 @ 300<br>Exendin-9,39 @ 300pmol/kg/min | Drug: Exendin-9,39<br>* use Exendin-9,39 @ 750pmol/kg/min and Exendin-9,39 @ 300pmol/kg/min to block endogenous GLP-1 in humans after gastric bypass and determine contribution of GLP to satiety after meal ingestion<br>|
| Active Comparator: Exendin-9,39 @ 750<br>Exendin-9,39 @ 750pmol/kg/min | Drug: Exendin-9,39<br>* use Exendin-9,39 @ 750pmol/kg/min and Exendin-9,39 @ 300pmol/kg/min to block endogenous GLP-1 in humans after gastric bypass and determine contribution of GLP to satiety after meal ingestion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calories consumed during buffet meal test | The calories consumed during buffet meal test at the end of each study test will help determine the effect of GLP-1 receptor blockade with Exendin-9,39 on food intake. | approximately 300 minutes after initiation |