To Define the Role of GLP-1 for Improving Glucose Homeostasis in Humans Following Gastric Bypass Surgery
Condition: Bypass, Gastric; Roux-en-Y Gastric Bypass; Vertical Sleeve Gastrectomy; Gastric Banding; Bariatric Surgery
Study type: Interventional
Phase: Phase 1

Summary: 
      There is a marked and long-lasting improvement in glucose homeostasis that follows Roux-en-y
      gastric bypass surgery (RYGB) in humans. This improvement has been attributed in large part
      to an intestinal hormone, called GLP-1, that is released into the circulation immediately
      after eating. The purpose of this study is to determine if GLP-1 mediates the beneficial
      effects of RYGB surgery on glucose homeostasis in humans.
    

Detailed description: 
      To conduct this study, we will enroll humans who previously underwent Roux-en-Y gastric
      bypass surgery, who are medically and weight stable and with no signs of type 2 diabetes
      either before or after surgery. Potential subjects will first be screened for eligibility and
      also to verify that they can safely participate in the study. Each study subject will be
      administered a meal tolerance test (MTT) on 3 separate occasions. For the MTT, a liquid meal
      (Boost Plus) will be ingested following an overnight fast. A primed-continuous infusion of
      vehicle alone (human albumin) or xenin-25 alone (at a dose of 4 or 12 pmoles x kg-1 x min-1)
      will be initiated 15 minutes before the meal is ingested. Blood samples will be collected
      before and during the MTT for the measurement of glucose and insulin levels, as well as a
      host of other hormones. A comparison of the results will tell us if the effects of xenin-25
      on insulin release are mediated by GLP-1 in humans.
    

Intervention name(s): Placebo; Lo-Xenin; Hi-Xenin; Extra Hi-Xenin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.
Starting at minus 15 minutes, an intravenous infusion of albumin alone (placebo) will be administered for 5.25 hours.; A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.
Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 4 pmoles/kg/min will be administered for 5.25 hours.; A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.
Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 12 pmoles/kg/min will be administered for 5.25 hours.; A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.
Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 24 pmoles/kg/min will be administered for 5.25 hours.
Other intervention name(s): Control; Albumin Alone; Lo-Xen; Hi-Xen; XHi-Xen
Intervention model: Crossover Assignment
Intervention model description: Patients with prior RYGB surgery receive all interventions, each on a separate day.
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Gastric Bypass; RYGB; GLP-1; Xenin; Insulin Secretion; Glucose Homeostasis; Vertical Sleeve; Lap Band