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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00949663
First received: July 28, 2009
Last updated: June 26, 2013
Last verified: June 2013

July 28, 2009
June 26, 2013
October 2009
June 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: 3 years ] [ Designated as safety issue: Yes ]
We will determine whether xenin-25 also enhances the insulin secretory response to GLP-1 in control and T2DM subjects. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00949663 on ClinicalTrials.gov Archive Site
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 ]
we will develop an assay to measure the normal fasting and postprandial concentrations of endogenous xenin-25 and to determine whether they are altered in T2DM. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function
Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function

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 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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • 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
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.

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

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.
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00949663
08-0861B, 1R01DK088126-01
Yes
Washington University School of Medicine
Washington University School of Medicine
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Burton Wice, PhD Washington University School of Medicine
Principal Investigator: Dominic Reeds, MD 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