Ignite Creation Date:
2025-12-26 @ 11:48 AM
Ignite Modification Date:
2025-12-26 @ 11:48 AM
Study NCT ID:
NCT01951716
Status:
WITHDRAWN
Last Update Posted:
2018-04-26
First Post:
2013-09-23
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Effects of Xenin-25 on Insulin Secretion and Gastric Emptying in Humans With and Without a Complete Truncal Vagotomy
Sponsor:
Washington University School of Medicine
Organization:
Study Overview
Official Title:
Effects of Xenin-25 on Insulin Secretion and Gastric Emptying in Humans With and Without a Complete Truncal Vagotomy
Status:
WITHDRAWN
Status Verified Date:
2018-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Glucose-dependent Insulinotropic Polypeptide (GIP) and xenin-25 are peptide hormones produced/released from your intestines and help regulate blood sugar levels after you eat. We have previously performed studies in humans that measured the effects of xenin-25 and GIP (alone and together) on blood sugar levels. One study was conducted with an intravenous infusion of glucose but without ingestion of a meal. In this study, xenin-25 increased the effects of GIP on insulin secretion- but only in humans without type 2 diabetes mellitus (T2DM). A second study was conducted in conjunction with ingestion of a meal. In this study, xenin-25 reduced blood glucose levels by delaying gastric emptying and this effect was similar in humans with and without T2DM. A variety of studies that we have performed suggest that xenin-25 works by activating nerves. A specific nerve called the vagus nerve plays an important role in regulating insulin secretion. This study will determine if the vagus nerve (which was disrupted if you had a vagotomy) is needed for the effects of xenin-25 on insulin secretion and/or gastric emptying.
Detailed Description:
Two groups of subjects, both without T2DM, will be studied. One group will consist of people who previously received a complete truncal vagotomy as part of a surgical treatment unrelated to this research project. The other group will be subjects who have not had a truncal vagotomy.
Initially, each potential participant will be administered an oral glucose tolerance test at the screening visit to make sure that they do not have type 2 diabetes. They will also have a sham feeding test to check for the completeness (or absence) of the vagotomy. As outlined below, each subject will then receive 4 graded glucose infusions (GGI) and 2 meal tolerance tests (MTT)- each on a separate occasion following an overnight fast.
For each GGI, the subject will be given an intravenous infusion of glucose such that blood glucose levels slowly increase over a 4 hour period. On separate occasions, the participant will also receive a primed-continuous infusion of GIP alone, xenin-25 alone, GIP plus xenin-25, or placebo (constant dose of 4 pmoles x kg-1 x min-1). Blood samples will be collected before and during the GGI for the measurement of glucose, insulin, C-peptide, glucagon, pancreatic polypeptide, GIP and xenin-25 levels. Insulin secretion rates will also be calculated. By comparing results for the two groups, we will learn if the vagus nerve mediates the effects of GIP, xenin-25, or the combination of GIP plus xenin-25 on insulin secretion in humans and thus, if this signaling circuit is impaired in humans with T2DM.
For the MTTs, the participant will ingest a liquid meal (Boost Plus) plus acetaminophen (Tylenol). On separate occasions, a primed-continuous infusion of vehicle alone or xenin-25 alone (constant dose of 12 pmoles x kg-1 x min-1) will be initiated at the same time the meal is ingested. Blood samples will be collected before and during the MTT for the measurement of acetaminophen, glucose, insulin, C-peptide, glucagon, GIP and xenin-25 levels. Insulin secretion rates will also be calculated. The rate of acetaminophen appearance in the blood is an indirect measure of the rate of gastric emptying. By comparing results for the two groups, we will learn if the vagus nerve mediates the effects of xenin-25 on gastric emptying in humans.
Initially, each potential participant will be administered an oral glucose tolerance test at the screening visit to make sure that they do not have type 2 diabetes. They will also have a sham feeding test to check for the completeness (or absence) of the vagotomy. As outlined below, each subject will then receive 4 graded glucose infusions (GGI) and 2 meal tolerance tests (MTT)- each on a separate occasion following an overnight fast.
For each GGI, the subject will be given an intravenous infusion of glucose such that blood glucose levels slowly increase over a 4 hour period. On separate occasions, the participant will also receive a primed-continuous infusion of GIP alone, xenin-25 alone, GIP plus xenin-25, or placebo (constant dose of 4 pmoles x kg-1 x min-1). Blood samples will be collected before and during the GGI for the measurement of glucose, insulin, C-peptide, glucagon, pancreatic polypeptide, GIP and xenin-25 levels. Insulin secretion rates will also be calculated. By comparing results for the two groups, we will learn if the vagus nerve mediates the effects of GIP, xenin-25, or the combination of GIP plus xenin-25 on insulin secretion in humans and thus, if this signaling circuit is impaired in humans with T2DM.
For the MTTs, the participant will ingest a liquid meal (Boost Plus) plus acetaminophen (Tylenol). On separate occasions, a primed-continuous infusion of vehicle alone or xenin-25 alone (constant dose of 12 pmoles x kg-1 x min-1) will be initiated at the same time the meal is ingested. Blood samples will be collected before and during the MTT for the measurement of acetaminophen, glucose, insulin, C-peptide, glucagon, GIP and xenin-25 levels. Insulin secretion rates will also be calculated. The rate of acetaminophen appearance in the blood is an indirect measure of the rate of gastric emptying. By comparing results for the two groups, we will learn if the vagus nerve mediates the effects of xenin-25 on gastric emptying in humans.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: