Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function
Information source: Washington University School of Medicine
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes Mellitus
Intervention: Placebo (Drug); Glucose-dependent Insulinotropic Polypeptide (GIP) (Drug); Xenin-25 (Drug); Glucose-dependent Insulinotropic Polypeptide plus Xenin-25 (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Washington University School of Medicine Official(s) and/or principal investigator(s): Burton Wice, PhD, Principal Investigator, Affiliation: Washington University School of Medicine Dominic Reeds, MD, Principal Investigator, Affiliation: Washington University School of Medicine
Summary
An intestinal hormone called Glucose-dependent Insulinotropic Polypeptide (GIP) is released
into the blood immediately after ingestion of a meal and plays an important role in
regulating blood sugar levels. However, GIP is not active in persons with type 2 diabetes
mellitus (T2DM) which is also known as adult onset or non-insulin-dependent diabetes. This
study is being conducted to determine whether a hormone called xenin-25 can restore the
activity of GIP in persons with T2DM.
Clinical Details
Official title: Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Primary outcome: The effects of GIP, xenin-25, or a combination of GIP plus xenin-25 on insulin secretion and blood glucose levels
Secondary outcome: We will develop an assay to measure the normal fasting and postprandial concentrations of endogenous xenin-25 and determine whether they are altered in T2DM.
Detailed description:
Each eligible participant will be administered an oral glucose tolerance test so he/she can
be assigned to the group with "normal glucose tolerance", "impaired glucose tolerance"
(between normal and diabetic), or type 2 diabetes mellitus. Each study subject will then be
administered a meal tolerance test (MTT) on 4 separate occasions. For the MTT, a liquid meal
(Boost Plus)will be ingested following an overnight fast. A primed-continuous infusion of
vehicle alone, GIP alone, xenin-25 alone, or the combination of GIP plus xenin-25 (each
peptide at a dose of 4 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
glucose, insulin, C-peptide, glucagon, GIP and xenin-25 levels.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Ages 18-65. 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 T2DM (see below).
- Otherwise healthy volunteers that have impaired glucose tolerance (see below).
- Otherwise healthy volunteers with Diet Controlled T2DM (see below).
- Otherwise healthy volunteers with T2DM that take oral agents only and if the
subject's pre-existing oral anti-diabetic agents can be safely discontinued for 48
hours prior to Oral Glucose Tolerance Test.
- Otherwise healthy volunteers with T2DM who do not use insulin for blood glucose
control.
- Persons with HbA1c ≤ 9%.
- 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.
Exclusion Criteria:
- <18years of age or >65 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.
- Any subject whose screening HbA1c is >9. 0%
- Type 2 diabetes requiring the use of supplemental insulin @ home
- 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.
- Diabetics that have the potential to have a low blood sugar without them being aware
that their blood sugar is low (hypoglycemia unawareness).
- 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.
Locations and Contacts
Washington University School of Medicine, St. Louis, Missouri 63110, United States
Additional Information
Starting date: October 2009
Last updated: July 21, 2014
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