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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00949663
First received: July 28, 2009
Last updated: July 21, 2014
Last verified: July 2014
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function

Resource links provided by NLM:


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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00949663

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Burton Wice, PhD Washington University School of Medicine
Principal Investigator: Dominic Reeds, MD Washington University School of Medicine
  More Information

No publications provided by Washington University School of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00949663     History of Changes
Other Study ID Numbers: 08-0861B, 1R01DK088126-01
Study First Received: July 28, 2009
Last Updated: July 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Diabetes
Blood Sugar
Xenin-25
GIP
Insulin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Gastric Inhibitory Polypeptide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 16, 2014