Effects of Xenin-25 on Insulin Secretion and Gastric Emptying in Humans With and Without a Complete Truncal Vagotomy

• Status: Withdrawn
• Trial end date: 2018-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborator: American Diabetes Association
• Treatments: Insulin

Criteria

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.