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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00798915
First received: November 24, 2008
Last updated: June 26, 2013
Last verified: June 2013

November 24, 2008
June 26, 2013
December 2008
December 2013   (final data collection date for primary outcome measure)
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 ]
the effects of a specific peptide (or combination of peptides) will be determined on each occasion for each protocol and thus, each visit represents an endpoint [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00798915 on ClinicalTrials.gov Archive Site
The effects of xenin-25 on GIP action in persons with type 2 diabetes [ Time Frame: 5yrs ] [ Designated as safety issue: Yes ]
second endpoint is after the third visit for each protocol for each subject. At this time, we will be able to determine whether Xenin-25 increases the action of GIP in persons with T2DM. This is the major endpoint for our studies [ Time Frame: 5yrs ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study of the Effects of Xenin-25 in Humans With and Without Type 2 Diabetes Mellitus
Restoration of the GIP-mediated Incretin Effect in Persons With Type 2 Diabetes Mellitus

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Diabetes
  • 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: Normal Glucose Tolerance
    Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
    Interventions:
    • Drug: Placebo
    • Drug: Glucose-dependent Insulinotropic Polypeptide (GIP)
    • Drug: Xenin-25
    • Drug: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Glucose-dependent Insulinotropic Polypeptide (GIP)
    • Drug: Xenin-25
    • Drug: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Glucose-dependent Insulinotropic Polypeptide (GIP)
    • Drug: Xenin-25
    • Drug: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25
Wice BM, Reeds DN, Tran HD, Crimmins DL, Patterson BW, Dunai J, Wallendorf MJ, Ladenson JH, Villareal DT, Polonsky KS. Xenin-25 amplifies GIP-mediated insulin secretion in humans with normal and impaired glucose tolerance but not type 2 diabetes. Diabetes. 2012 Jul;61(7):1793-800. doi: 10.2337/db11-1451. Epub 2012 Apr 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
December 2013
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00798915
08-0861A, 1RC1DK086163-01
Yes
Washington University School of Medicine
Washington University School of Medicine
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Dominic Reeds, MD Washington University School of Medicine
Principal Investigator: Burton Wice, PhD Washington University School of Medicine
Washington University School of Medicine
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP