Facilitated Release of Endogenous Enterokines

Study Overview
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Brief Summary
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The overall objective is to develop therapy for obesity and diabetes that is as effective as gastric bypass surgery but without the cost and safety concerns.

Detailed Description
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Gastric bypass leads to rapid, sustained diabetes remission in the majority of patients who undergo this procedure and is also highly effective therapy for obesity. However, currently <1% of medically-eligible patients undergo this or other bariatric operations due to cost and safety concerns. The approach is based on data suggesting that the benefit of gastric bypass is largely due to anatomical rearrangement of the intestine which leads to accelerated delivery of nutrients to the jejunum. This rerouting of nutrients stimulates the release of multiple neural, hormonal and enterokine responses that are associated with appetite suppression and improved glucose control. In this pilot proposal the question under investigation is whether repeated rapid delivery of a mixed meal directly to the jejunum can promote weight loss and glucose control.

Official Title
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Facilitated Release of Endogenous Enterokines: An Ambulatory Prospective Randomized Controlled Trial

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Dietary Supplement: Mixed-Meal
* Dietary Supplement: Electrolyte Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes on oral antidiabetic medication BMI greater than or equal to 30kg/m2 A1C less than 9% Exclusion Criteria: Use of any of the following medications: dipeptide-peptidase IV (DPP-IV) inhibitors (e.g., sitagliptin), GLP-1 analogs (e.g., exenatide) or medication that could alter glucose tolerance (e.g. steroids) Contraindication to tube (e.g. Prior upper gastrointestinal bleed, or history of easy bleeding, altered foregut anatomy due to obstruction or surgery) Known cardiovascular disease other than controlled hypertension. Pregnancy or unwilling to take contraception Active esophagitis Known hiatal hernia Active gastric ulcer and/or duodenal ulcers, Previous restrictive surgery of the gastrointestinal tract Crohn's disease Active cancer History of gastrointestinal hemorrhage Known upper gastrointestinal lesions with potential to bleed Use of NSAIDs or anticoagulants Psychiatric disorders other than mild depression Likely inability to adhere to study protocol including alcohol or drug dependent patients Type I diabetes, Liver, kidney or multi-organ dysfunction. Known eating disorders Inability to attend scheduled or unanticipated study visits Known prior abdominal problems or operations that could lead to adhesions or strictures and that could prevent the spontaneous passage of a 10 French jejunal tube if it were to dislodge distally.

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mixed-Meal<br>Ensure Nutrition Shake | Dietary Supplement: Mixed-Meal<br>* Per 250ml bottle: 220 calories, protein 9g, carbohydrate 33g (15g sugar), fat 6g, sodium 190mg, potassium 390mg; 500mLs by tube daily in 4 doses<br>* Other names: Ensure Nutrition Shake® (Abbott Park, Illinois, U.S.A.);|
| Placebo Comparator: Electrolyte Solution<br>Pedialyte Solution | Dietary Supplement: Electrolyte Solution<br>* Electrolyte Solution 500mLs by tube daily in 4 doses<br>* Other names: Unflavored Pedialyte ® (Abbott Park, Illinois, U.S.A.);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight change between groups | Weight measured in kilograms taken before and immediately following the intervention period between the intervention and control group | Day 0 to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Caloric intake within and between groups | Caloric intake measured in kcal. Determined by consumption of provided food. | Day 0 to Day 14 | 
| Weight change within group | Weight measured in kilgrams. Within group | Day 0 to Day 14 | 
| Change in waist and hip measurements | Measured in centimeters. Between groups. | Day 0 to Day 14 | 
| Change in systolic and diastolic blood pressure | Measured in mmHg for both. Between groups. | Day 0 to Day 14 | 
| Change in heart rate | Measured in beats per minute. Between groups. | Day 0 to Day 14 | 
| Changes in gut hormone levels | Including GLP-1, PYY, CCK, C-peptide, and insulin. Between groups. | Day 0 to Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Diabetes Mellitus, Type 2, Nutrient