Study of the Effects of Xenin-25 in Humans With and Without Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00798915
First received: November 24, 2008
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
Diabetes
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: Restoration of the GIP-mediated Incretin Effect in Persons With Type 2 Diabetes Mellitus

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: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The effects of xenin-25 on GIP action in persons with type 2 diabetes [ Time Frame: 5yrs ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: December 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (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 graded glucose infusion (GGI) on 4 separate occasions. For the GGI, an intravenous glucose infusion will be started at a rate of 1 mg x kg-1 x min-1 for 40 min, followed by 2, 3, 4, 6, and 8 mg x kg-1 x min-1 (40 min for each step). 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 glucose infusion is started. Blood samples will be collected before and during the GGI 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:

  • 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.
  • Otherwise healthy volunteers that have impaired glucose tolerance.
  • Otherwise healthy volunteers with diet controlled T2DM.
  • Otherwise healthy volunteers with T2DM that take oral agents only if the subject's pre-existing oral anti-diabetic agents can be safely discontinued for 48-hours.
  • Persons with HbA1c less than 9%.
  • Women of childbearing potential must be currently taking/using an acceptable method of birth control. 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:

  • Lacks cognitive ability to sign the consent or follow the study directions.
  • Women unwilling to use 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 at home.
  • Volunteers with a history of Acute Pancreatitis.
  • Volunteers with a history of cancer (except for skin cancer).
  • 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.
  • Subjects taking medications known to affect glucose tolerance.
  • Hematocrit from the lab is below 33% (or if the finger stick hemoglobin measured with the HemoCue 201+ is <11.2% mg/dlL).
  • Diabetics that have the potential to have a low blood sugar without them being aware that their blood sugar is low (hypoglycemia unawareness).
  • Significant systemic illness including heart, kidney, inflammatory, liver, or malignant disease requiring medications.
  • Subjects will be excluded if their liver or kidney function is outside the upper limits of normal by > 3%. Total Bilirubin levels should be <2.
  • Subjects unwilling to allow the use of 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: NCT00798915

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: Dominic Reeds, MD Washington University School of Medicine
Principal Investigator: Burton Wice, PhD 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: NCT00798915     History of Changes
Other Study ID Numbers: 08-0861A, 1RC1DK086163-01
Study First Received: November 24, 2008
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
Gastric Inhibitory Polypeptide
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014