Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00949663
• Other study ID #: 08-0861B
• Secondary ID: 1R01DK088126-01
• Status: Completed
• Phase: Phase 1
• First received: July 28, 2009
• Last updated: July 21, 2014
• Start date: October 2009
• Est. completion date: February 2014

Study information

• Verified date: July 2014
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Placebo
Intravenous infusion of 1% human albumin in normal saline
• Glucose-dependent Insulinotropic Polypeptide (GIP)
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
• Xenin-25
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
• Glucose-dependent Insulinotropic Polypeptide plus Xenin-25
Intravenous infusion of GIP plus xenin-25 (4 pmoles each x kg-1 x min-1) in 1% human albumin in normal saline

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The effects of GIP, xenin-25, or a combination of GIP plus xenin-25 on insulin secretion and blood glucose levels		3 years	Yes
Secondary	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.		3 years	No