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

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT00949663

First Posted: July 30, 2009

Last Update Posted: July 22, 2014

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Collaborator:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Information provided by (Responsible Party):

Washington University School of Medicine

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Placebo Drug: Glucose-dependent Insulinotropic Polypeptide (GIP) Drug: Xenin-25 Drug: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Crossover Assignment Masking: Single (Participant) Primary Purpose: Treatment
Official Title:	Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function

Resource links provided by NLM:

Drug Information available for: Insulin

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:

The effects of GIP, xenin-25, or a combination of GIP plus xenin-25 on insulin secretion and blood glucose levels [ Time Frame: 3 years ]

Secondary Outcome Measures:

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. [ Time Frame: 3 years ]


Enrollment:	38
Study Start Date:	October 2009
Study Completion Date:	February 2014
Primary Completion Date:	February 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Normal Glucose Tolerance Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.	Drug: Placebo Intravenous infusion of 1% human albumin in normal saline Other Name: Vehicle Alone Drug: Glucose-dependent Insulinotropic Polypeptide (GIP) Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline Other Name: GIP Drug: Xenin-25 Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline Other Name: Xenin Drug: 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 Other Name: GIP plus Xenin
Experimental: Impaired Glucose Tolerance Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.	Drug: Placebo Intravenous infusion of 1% human albumin in normal saline Other Name: Vehicle Alone Drug: Glucose-dependent Insulinotropic Polypeptide (GIP) Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline Other Name: GIP Drug: Xenin-25 Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline Other Name: Xenin Drug: 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 Other Name: GIP plus Xenin
Experimental: Type 2 Diabetes Mellitus Healthy individuals exhibiting plasma glucose levels greater than 150 mg/dL under fasting conditions OR greater than 199 mg/dl two hours after ingestion of 75-g of glucose.	Drug: Placebo Intravenous infusion of 1% human albumin in normal saline Other Name: Vehicle Alone Drug: Glucose-dependent Insulinotropic Polypeptide (GIP) Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline Other Name: GIP Drug: Xenin-25 Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline Other Name: Xenin Drug: 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 Other Name: GIP plus Xenin

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

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Information from the National Library of Medicine

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): NCT00949663

Locations


United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators


Principal Investigator:	Burton Wice, PhD	Washington University School of Medicine
Principal Investigator:	Dominic Reeds, MD	Washington University School of Medicine

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chowdhury S, Reeds DN, Crimmins DL, Patterson BW, Laciny E, Wang S, Tran HD, Griest TA, Rometo DA, Dunai J, Wallendorf MJ, Ladenson JH, Polonsky KS, Wice BM. Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without type 2 diabetes. Am J Physiol Gastrointest Liver Physiol. 2014 Feb 15;306(4):G301-9. doi: 10.1152/ajpgi.00383.2013. Epub 2013 Dec 19.


Responsible Party:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00949663 History of Changes
Other Study ID Numbers:	08-0861B 1R01DK088126-01 ( U.S. NIH Grant/Contract )
First Submitted:	July 28, 2009
First Posted:	July 30, 2009
Last Update Posted:	July 22, 2014
Last Verified:	July 2014

Keywords provided by Washington University School of Medicine:


Diabetes Blood Sugar Xenin-25 GIP Insulin

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Insulin Gastric Inhibitory Polypeptide	Hypoglycemic Agents Physiological Effects of Drugs Gastrointestinal Agents Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists

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