Effect of Ghrelin on Glucose Metabolism After Bariatric Surgery
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Vertical Sleeve Gastrectomy (VSG) NJ/PO 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)
Subjects will have glucose administered enterally and blood will be drawn to measure its kinetics.
Other Names:
Drug: Human Ghrelin
Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.
Other Names:
Drug: Saline
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.
Other Names:
|
| Experimental: Roux-en-Y Gastric Bypass (RYGB) NJ/PO 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)
Subjects will have glucose administered enterally and blood will be drawn to measure its kinetics.
Other Names:
Drug: Human Ghrelin
Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.
Other Names:
Drug: Saline
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.
Other Names:
|
| Experimental: Vertical Sleeve Gastrectomy (VSG) PO/PO 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)
Subjects will have glucose administered enterally and blood will be drawn to measure its kinetics.
Other Names:
Drug: Human Ghrelin
Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.
Other Names:
Drug: Saline
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.
Other Names:
|
| Experimental: Roux-en-Y Gastric Bypass (RYGB) PO/PO 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)
Subjects will have glucose administered enterally and blood will be drawn to measure its kinetics.
Other Names:
Drug: Human Ghrelin
Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.
Other Names:
Drug: Saline
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in plasma glucose levels with ghrelin versus saline. [1 month (before and after surgery)]
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).
Secondary Outcome Measures
- Plasma insulin levels [1 month (before and after surgery)]
Other Outcome Measures
- Plasma Levels of GLP-1 [1 month (before and after surgery)]
Metabolic panel to include plasma levels of GLP-1
- Plasma Levels of GIP [1 month (before and after surgery)]
Metabolic panel to include plasma levels of GIP
- Plasma Levels of leptin [1 month (before and after surgery)]
Metabolic panel to include plasma levels of leptin
- Plasma Levels of pancreatic polypeptide [1 month (before and after surgery)]
Metabolic panel to include plasma levels of pancreatic polypeptide
- Plasma Levels of Peptide YY (PYY) [1 month (before and after surgery)]
Metabolic panel to include plasma levels of PYY
- Plasma Levels of C-Peptide [1 month (before and after surgery)]
Metabolic panel to include plasma levels of C-Peptide
- Plasma Levels of glucagon [1 month (before and after surgery)]
Metabolic panel to include plasma levels of glucagon
- Plasma Levels of Cholecystokinin (CCK) [1 month (before and after surgery)]
- Plasma Levels of Cholecystokinin Adrenocorticotropic Hormone (ACTH) [1 month (before and after surgery)]
- Plasma Levels of Human Growth Hormone (HGH) [1 month (before and after surgery)]
- Plasma Levels of Cortisol [1 month (before and after surgery)]
- Plasma Levels of insulin-like growth factor 1 (IGF-1) [1 month (before and after surgery)]
- Acyl and desacyl ghrelin [1 month (before and after surgery)]
- Plasma Levels of Bile Acids [1 month (before and after surgery)]
- Plasma Levels of Free Fatty Acids (FFAs) [1 month (before and after surgery)]
- Plasma Levels of Triglycerides (TG) [1 month (before and after surgery)]
- Performance on Visual Analog Scale for Hunger [1 month (before and after surgery)]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
Sponsors and Collaborators
- Vanderbilt University Medical Center
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 111237-Protocol II
- R01DK091748