Effects of Xenin-25 on Insulin Secretion and Gastric Emptying in Humans With and Without a Complete Truncal Vagotomy
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| ClinicalTrials.gov Identifier: NCT01951716 |
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Recruitment Status :
Withdrawn
First Posted : September 27, 2013
Last Update Posted : April 26, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Does the Vagus Nerve Mediate the Effects of Xenin-25 | Drug: Graded Glucose Infusion with Placebo Drug: Graded Glucose Infusion with GIP Alone Drug: Graded Glucose Infusion with xenin-25 alone Drug: Graded Glucose Infusion with GIP plus xenin-25 Drug: Meal Tolerance Test with Placebo Drug: Meal Tolerance Test with xenin-25 | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 0 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Single (Participant) |
| Primary Purpose: | Treatment |
| Official Title: | Effects of Xenin-25 on Insulin Secretion and Gastric Emptying in Humans With and Without a Complete Truncal Vagotomy |
| Study Start Date : | January 2013 |
| Estimated Primary Completion Date : | July 2018 |
| Estimated Study Completion Date : | July 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Truncal Vagotomy
Healthy participants without diabetes who have undergone a complete truncal vagotomy
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Drug: Graded Glucose Infusion with Placebo
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. Other Name: GGI with Albumin Alone Drug: Graded Glucose Infusion with GIP Alone Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of GIP in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. Other Name: GGI with GIP Drug: Graded Glucose Infusion with xenin-25 alone Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. Other Name: GGI with Xenin Drug: Graded Glucose Infusion with GIP plus xenin-25 Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of GIP plus xenin-25 in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. Other Name: GGI with GIP plus Xenin Drug: Meal Tolerance Test with Placebo At 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested. Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 300 minutes. The study is finished at 300 minutes. Other Name: MTT with Albumin Alone Drug: Meal Tolerance Test with xenin-25 At 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested. Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 300 minutes. The study is finished at 300 minutes. Other Name: MTT with xenin |
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Experimental: No Vagotomy
Healthy participants without diabetes who have not had a complete truncal vagotomy
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Drug: Graded Glucose Infusion with Placebo
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. Other Name: GGI with Albumin Alone Drug: Graded Glucose Infusion with GIP Alone Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of GIP in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. Other Name: GGI with GIP Drug: Graded Glucose Infusion with xenin-25 alone Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. Other Name: GGI with Xenin Drug: Graded Glucose Infusion with GIP plus xenin-25 Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of GIP plus xenin-25 in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. Other Name: GGI with GIP plus Xenin Drug: Meal Tolerance Test with Placebo At 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested. Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 300 minutes. The study is finished at 300 minutes. Other Name: MTT with Albumin Alone Drug: Meal Tolerance Test with xenin-25 At 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested. Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 300 minutes. The study is finished at 300 minutes. Other Name: MTT with xenin |
- Insulin secretion rates will be measured during the GGI and MTTs [ Time Frame: 3 years ]
- Plasma acetaminophen levels will be measured during MTTs [ Time Frame: 3 years ]
- Plasma glucose levels will be measured during the GGIs and MTTs. [ Time Frame: 3 years ]
- Plasma glucagon levels will be measured during the GGIs and MTTs. [ Time Frame: 3 years ]
- Plasma insulin levels will be measured during the GGIs and MTTs. [ Time Frame: 3 years ]
- Plasma C-peptide levels will be measured during the GGIs and MTTs. [ Time Frame: 3 years ]
- Plasma pancreatic polypeptide levels will be measured during the GGIs and MTTs. [ Time Frame: 3 years ]
- Plasma GIP levels will be measured during the GGIs and MTTs. [ Time Frame: 3 years ]
- Plasma xenin-25 levels will be measured during the GGIs and MTTs. [ Time Frame: 3 years ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Ages 18-70. No minors will be studied.
- Individuals must be able to consent for their own participation (no mental impairment affecting cognition or willingness to follow study instructions).
- Healthy volunteers with no clinical evidence of Type 2 Diabetes
- Healthy volunteers who have undergone a complete truncal vagotomy
- Healthy volunteers who have not had a complete truncal vagotomy
- 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 complete all required visits
Exclusion Criteria:
- <18years of age or >70 years of age
- 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 Type 2 diabetes
- Volunteers with a history of Acute Pancreatitis
- 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.
- Volunteers with a history of gastrointestinal disorders, particularly related to gastric motility/emptying such as gastric bypass, documented gastro-paresis in diabetic volunteers.
- Volunteers with a history of cancer. Exception: skin cancer.
- Known heart, kidney. liver or pancreatic disease requiring medications.
- Subjects unwilling to allow the use of their own blood or the human albumin in the preparation of the peptides.
- Unwillingness to allow blood glucose level adjustment (if needed) with IV insulin.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01951716
| United States, Missouri | |
| Washington University School of Medicine | |
| Saint Louis, Missouri, United States, 63110 | |
| Principal Investigator: | Burton M Wice, PhD | Washington University School of Medicine | |
| Principal Investigator: | Dominic Reeds, MD | Washington University School of Medicine |
| Responsible Party: | Washington University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT01951716 |
| Other Study ID Numbers: |
08-0861 D |
| First Posted: | September 27, 2013 Key Record Dates |
| Last Update Posted: | April 26, 2018 |
| Last Verified: | April 2018 |
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Vagotomy Vagus Nerve Xenin-25 GIP |
Insulin Secretion Glucagon Secretion Gastric Emptying |