Effect of Ghrelin on Glucose Metabolism After Bariatric Surgery

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Procedure: Oral Glucose Tolerance Test (OGTT); Drug: Human Ghrelin; Drug: Saline

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / 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: OGTT; Drug: Human Ghrelin; Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.; Other Names: Ghrelin; 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: NaCl, sodium chloride
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: OGTT; Drug: Human Ghrelin; Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.; Other Names: Ghrelin; 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: NaCl, sodium chloride
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: OGTT; Drug: Human Ghrelin; Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.; Other Names: Ghrelin; 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: NaCl, sodium chloride
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: OGTT; Drug: Human Ghrelin; Human ghrelin will be administered by IV at two of the four study visits in conjunction with the OGTT.; Other Names: Ghrelin; 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: NaCl, sodium chloride

What is the study measuring?

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	Time Frame
Plasma insulin levels	1 month (before and after surgery)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Levels of GLP-1	Metabolic panel to include plasma levels of GLP-1	1 month (before and after surgery)
Plasma Levels of GIP	Metabolic panel to include plasma levels of GIP	1 month (before and after surgery)
Plasma Levels of leptin	Metabolic panel to include plasma levels of leptin	1 month (before and after surgery)
Plasma Levels of pancreatic polypeptide	Metabolic panel to include plasma levels of pancreatic polypeptide	1 month (before and after surgery)
Plasma Levels of Peptide YY (PYY)	Metabolic panel to include plasma levels of PYY	1 month (before and after surgery)
Plasma Levels of C-Peptide	Metabolic panel to include plasma levels of C-Peptide	1 month (before and after surgery)
Plasma Levels of glucagon	Metabolic panel to include plasma levels of glucagon	1 month (before and after surgery)
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)

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (ACTUAL): August 21, 2019
• Study Completion (ACTUAL): January 30, 2023

Study Registration Dates

• First Submitted: September 22, 2016
• First Submitted That Met QC Criteria: October 31, 2016
• First Posted (ESTIMATE): November 3, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Obesity; Bariatric Surgery
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: 111237-Protocol II; R01DK091748 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No