Effect of Ghrelin on Glucose Metabolism After Bariatric Surgery

Study Overview
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Brief Summary
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The purpose of this study is to determine if the altered nutrient exposure to the GI tract after bariatric surgery reveals a negative incretin effect of ghrelin.

Official Title
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Effect of Ghrelin on Glucose Metabolism After Bariatric Surgery

Conditions
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Obesity

Intervention / Treatment
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* Procedure: Oral Glucose Tolerance Test (OGTT)
* Drug: Human Ghrelin
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI ≥ 35 kg/m2 Age 21-65 years Weight ≤ 200 kg Exclusion Criteria: Type 2 or Type 1 diabetes Medications that alter insulin sensitivity or carbohydrate metabolism Positive pregnancy test Known history of intestinal diseases including, but not limited to, inflammatory bowel disease (e.g. Chronic Ulcerative Colitis, Crohn's disease, celiac sprue) Prior gastric or intestinal surgery or pancreas resection History of cardiovascular disease, including but not limited to: myocardial infarction, angioplasty, arrhythmia, uncontrolled hypertension History of chronic kidney disease or renal insufficiency; creatinine > 1.8 mg/dl. History of chronic liver disease, including but not limited to: cirrhosis, hepatitis, portal hypertension; AST and/or ALT > 2x the upper limit of normal. Abnormal ECG

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vertical Sleeve Gastrectomy (VSG) NJ/PO<br>Patients that are undergoing routine VSG will be studied preoperatively, and at 1 month postoperatively. Each time point will have two study visits with a cross-over design. The first visit at each time point will be randomized to a human ghrelin or a saline infusion, with the alternate infusion at the second visit. At each study visit, an Oral Glucose Tolerance Test (OGTT) will be performed by administering glucose through a nasojejunal (NJ) feeding tube preoperatively and orally (PO) postoperatively. | Procedure: Oral Glucose Tolerance Test (OGTT)<br>* Subjects will have glucose administered enterally and blood will be drawn to measure its kinetics.<br>* Other names: OGTT;Drug: Human Ghrelin<br>* Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.<br>* Other names: Ghrelin;Drug: Saline<br>* Saline Infusion will be administered by IV at two of the four study visits in conjunction with the OGTT to serve as a placebo comparator for the human ghrelin infusions.<br>* Other names: NaCl, sodium chloride;|
| Experimental: Roux-en-Y Gastric Bypass (RYGB) NJ/PO<br>Patients that are undergoing routine RYGB will be studied preoperatively, and at 1 month postoperatively. Each time point will have two study visits with a cross-over design. The first visit at each time point will be randomized to a human ghrelin or a saline infusion, with the alternate infusion at the second visit. At each study visit, an Oral Glucose Tolerance Test (OGTT) will be performed by administering glucose through a nasojejunal (NJ) feeding tube preoperatively and orally (PO) postoperatively. | Procedure: Oral Glucose Tolerance Test (OGTT)<br>* Subjects will have glucose administered enterally and blood will be drawn to measure its kinetics.<br>* Other names: OGTT;Drug: Human Ghrelin<br>* Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.<br>* Other names: Ghrelin;Drug: Saline<br>* Saline Infusion will be administered by IV at two of the four study visits in conjunction with the OGTT to serve as a placebo comparator for the human ghrelin infusions.<br>* Other names: NaCl, sodium chloride;|
| Experimental: Vertical Sleeve Gastrectomy (VSG) PO/PO<br>Patients that are undergoing routine VSG will be studied preoperatively, and at 1 month postoperatively. Each time point will have two study visits with a cross-over design. The first visit at each time point will be randomized to a human ghrelin or a saline infusion, with the alternate infusion at the second visit. At each study visit, an Oral Glucose Tolerance Test (OGTT) will be performed. | Procedure: Oral Glucose Tolerance Test (OGTT)<br>* Subjects will have glucose administered enterally and blood will be drawn to measure its kinetics.<br>* Other names: OGTT;Drug: Human Ghrelin<br>* Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.<br>* Other names: Ghrelin;Drug: Saline<br>* Saline Infusion will be administered by IV at two of the four study visits in conjunction with the OGTT to serve as a placebo comparator for the human ghrelin infusions.<br>* Other names: NaCl, sodium chloride;|
| Experimental: Roux-en-Y Gastric Bypass (RYGB) PO/PO<br>Patients that are undergoing routine RYGB will be studied preoperatively, and at 1 month postoperatively. Each time point will have two study visits with a cross-over design. The first visit at each time point will be randomized to a human ghrelin or a saline infusion, with the alternate infusion at the second visit. At each study visit, an Oral Glucose Tolerance Test (OGTT) will be performed. | Procedure: Oral Glucose Tolerance Test (OGTT)<br>* Subjects will have glucose administered enterally and blood will be drawn to measure its kinetics.<br>* Other names: OGTT;Drug: Human Ghrelin<br>* Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.<br>* Other names: Ghrelin;Drug: Saline<br>* Saline Infusion will be administered by IV at two of the four study visits in conjunction with the OGTT to serve as a placebo comparator for the human ghrelin infusions.<br>* Other names: NaCl, sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma glucose levels with ghrelin versus saline. | The objective for this protocol is to determine if ghrelin infusion worsens glucose tolerance during jejunal administration of glucose and if the response is difference after bariatric surgery (RYGB or VSG). | 1 month (before and after surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma insulin levels |  | 1 month (before and after surgery) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Bariatric Surgery