To Define the Role of GLP-1 for Improving Glucose Homeostasis in Humans Following Gastric Bypass Surgery
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Insulin secretion rates (ISRs) during each treatment
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals must be able to consent for their own participation (no mental impairment affecting cognition or willingness to follow study instructions).
- •Healthy, weight stable, with previous Roux-en-Y gastric bypass surgery and no clinical evidence of type 2 diabetes either before and after Roux-en-Y gastric bypass surgery.
- •Women of childbearing potential must be currently taking/using a method of birth control that is acceptable to the investigators. A pregnancy test will be done at the beginning of each visit. Any woman with a positive pregnancy test will be removed from the study.
- •Willingness to return have 8-10ml of blood drawn 25-30 days after the last Xenin infusion; to check for Xenin peptide antibodies that MAY develop. (All efforts will be made to complete this visit during study participation.)
排除标准
- •Lacks cognitive ability to sign the consent &/or follow the study directions for themselves.
- •Women unwilling to comply with using an acceptable method of contraception during the course of the study, or who are currently breast-feeding.
- •Volunteers with a history of Acute Pancreatitis.
- •Volunteers with a history of cancer (except for skin cancer).
- •Volunteer with a history of Chronic Pancreatitis and/or risk factors for chronic pancreatitis including hypertriglyceridemia (triglycerides >400mg/ml) hypercalcemia (blood calcium level >11.md/dl) and/or the presence of gallstones.
- •Subjects taking medications known to affect glucose tolerance.
- •Hematocrit from the lab is below 33% (or if the finger stick hemoglobin measured with the HemoCue 201+ is <11.2 g/dl).
- •Any major medical conditions, or conditions that in the opinion of the PI make the subject unsuitable for the study.
- •Subjects with abnormal kidney function as measured by the Creatinine concentration will be excluded.
- •Subjects with a history of active liver disease or AST/ALT levels >2X upper limit of normal will also be excluded.
- •Total Bilirubin levels should be <
- •Subjects unwilling to allow the use of their own blood or albumin in the preparation of the peptides. (The blood will prevent sticking of the peptide to the tubing; an alternative method has been sought but not found.)
- •Unwillingness to return have 8-10ml of blood drawn 25-30 days after the last Xenin infusion; to check for Xenin peptide antibodies that MAY develop. (All efforts will be made to complete this visit during study participation.)
研究组 & 干预措施
Post RYGB Surgery
Healthy, weight stable individuals, with previous Roux-en-Y gastric bypass surgery. No clinical evidence of type 2 diabetes before and after surgery. Each participant will receive placebo or the indicated doses of xenin-25.
干预措施: Placebo (Drug)
Post RYGB Surgery
Healthy, weight stable individuals, with previous Roux-en-Y gastric bypass surgery. No clinical evidence of type 2 diabetes before and after surgery. Each participant will receive placebo or the indicated doses of xenin-25.
干预措施: Lo-Xenin (Drug)
Post RYGB Surgery
Healthy, weight stable individuals, with previous Roux-en-Y gastric bypass surgery. No clinical evidence of type 2 diabetes before and after surgery. Each participant will receive placebo or the indicated doses of xenin-25.
干预措施: Hi-Xenin (Drug)
Post RYGB Surgery
Healthy, weight stable individuals, with previous Roux-en-Y gastric bypass surgery. No clinical evidence of type 2 diabetes before and after surgery. Each participant will receive placebo or the indicated doses of xenin-25.
干预措施: Extra Hi-Xenin (Drug)
结局指标
主要结局
Insulin secretion rates (ISRs) during each treatment
时间窗: 5.5 hours
ISRs will be measured at various times before and after ingestion of a liquid mixed meal.
次要结局
- Plasma glucagon levels during each treatment.(5.5 hours)
- Plasma glucose levels during each treatment.(5.5 hours)
- Plasma C-peptide levels during each treatment.(5.5 hours)
- Plasma GLP-1 during each treatment.(5.5 hours)
- The rate of gastric emptying during each treatment.(5.5 hours)