Exenatide on GI Motor Function and Permeability in Short Bowel Syndrome

Study Overview
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Brief Summary
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We plan to examine the gastrointestinal (GI) physiologic profile of Exenatide, a glucagon-like peptide (GLP-1) analog as a possible intestino-trophic growth factor capable of inducing small bowel adaptation and regeneration in patients with short bowel syndrome (SBS), with the potential to decrease parenteral nutrition dependence.

Official Title
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Acute Effects of a Glucagon-like Peptide 1 Analog, Exenatide, on Gastrointestinal Motor Function and Permeability in Patients With Short Bowel Syndrome on Home Parenteral Nutrition

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: Exenatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Patients with short bowel syndrome, between the ages of 18-85 who are dependent on parenteral nutrition for at least a year and are being closely followed by the Mayo Clinic Home Parenteral Nutrition Program (HPN) with at least one multisystem evaluation a year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide<br>Qualifying participants will be assigned to 2 different treatment arms consisting of placebo or exenatide 5 mcg administered subcutaneously twice: the first dose during fasting and the second four hours later. Subsequently, participants will switch over to the alternate treatment arm. In both arms participants will undergo a series of measurements including 24 hour GI transit, permeability measurements by using mannitol and lactulose, and 24 hour urine and stool collections. | Drug: Exenatide<br>* Qualifying participants will be assigned to 2 different treatment arms consisting of placebo or exenatide 5 mcg administered subcutaneously twice: the first dose during fasting and the second four hours later. Subsequently, participants will switch over to the alternate treatment arm. In both arms participants will undergo a series of measurements including 24 hour GI transit, permeability measurements by using mannitol and lactulose, and 24 hour urine and stool collections.<br>|
| Placebo Comparator: Placebo<br>Qualifying participants will be assigned to 2 different treatment arms consisting of placebo or exenatide 5 mcg administered subcutaneously twice: the first dose during fasting and the second four hours later. Subsequently, participants will switch over to the alternate treatment arm. In both arms participants will undergo a series of measurements including 24 hour GI transit, permeability measurements by using mannitol and lactulose, and 24 hour urine and stool collections. | Drug: Placebo<br>* Qualifying participants will be assigned to 2 different treatment arms consisting of placebo or exenatide 5 mcg administered subcutaneously twice: the first dose during fasting and the second four hours later. Subsequently, participants will switch over to the alternate treatment arm. In both arms participants will undergo a series of measurements including 24 hour GI transit, permeability measurements by using mannitol and lactulose, and 24 hour urine and stool collections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24hr Gastrointestinal and Colonic Transit before and after Exenatide vs placebo | To measure gastric, small intestinal and colonic (if applicable) transit in patients with short bowel syndrome (SBS) before and after the administration of Exenatide compared to placebo | In both arms participants will undergo GI transit measurements on 2 seperate occasions for a total of 24 hours, with a wash out period of 48 hours in between transit studies. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24hr Intestinal Permeability before and after administration of Exenatide vs placebo | To measure intestinal permeability to mannitol and lactulose in patients with short bowel syndrome before and after administration of Exenatide compared to placebo | In both arms participants will undergo intestinal permeability measurements on 2 seperate occasions for 24 hours,with a wash out period of 48 hours in between permeability studies. . |