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

Primary Purpose

Diabetes

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Placebo
Glucose-dependent Insulinotropic Polypeptide (GIP)
Xenin-25
Glucose-dependent Insulinotropic Polypeptide plus Xenin-25
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes focused on measuring Diabetes, Blood Sugar, Xenin-25, GIP, Insulin

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Normal Glucose Tolerance

Impaired Glucose Tolerance

Type 2 diabetes mellitus

Arm Description

Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.

Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.

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.

Outcomes

Primary Outcome Measures

The effects of GIP, xenin-25, or a combination of GIP plus xenin-25 on insulin secretion and blood glucose levels

Secondary Outcome Measures

The effects of xenin-25 on GIP action in persons with type 2 diabetes

Full Information

First Posted
November 24, 2008
Last Updated
April 30, 2018
Sponsor
Washington University School of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00798915
Brief Title
Study of the Effects of Xenin-25 in Humans With and Without Type 2 Diabetes Mellitus
Official Title
Restoration of the GIP-mediated Incretin Effect in Persons With Type 2 Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes
Keywords
Diabetes, Blood Sugar, Xenin-25, GIP, Insulin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Normal Glucose Tolerance
Arm Type
Experimental
Arm Description
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Arm Title
Impaired Glucose Tolerance
Arm Type
Experimental
Arm Description
Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Arm Title
Type 2 diabetes mellitus
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Vehicle alone
Intervention Description
Intravenous infusion of 1% human albumin in normal saline
Intervention Type
Drug
Intervention Name(s)
Glucose-dependent Insulinotropic Polypeptide (GIP)
Other Intervention Name(s)
GIP
Intervention Description
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Intervention Type
Drug
Intervention Name(s)
Xenin-25
Other Intervention Name(s)
Xenin
Intervention Description
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Intervention Type
Drug
Intervention Name(s)
Glucose-dependent Insulinotropic Polypeptide plus Xenin-25
Other Intervention Name(s)
GIP plus Xenin
Intervention Description
Intravenous infusion of GIP plus xenin-25 (4 pmoles each x kg-1 x min-1) in 1% human albumin in normal saline
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
The effects of xenin-25 on GIP action in persons with type 2 diabetes
Time Frame
5yrs

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dominic Reeds, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Burton Wice, PhD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24183983
Citation
Chowdhury S, Wang S, Patterson BW, Reeds DN, Wice BM. The combination of GIP plus xenin-25 indirectly increases pancreatic polypeptide release in humans with and without type 2 diabetes mellitus. Regul Pept. 2013 Nov 10;187:42-50. doi: 10.1016/j.regpep.2013.10.003. Epub 2013 Oct 29.
Results Reference
result
PubMed Identifier
22522617
Citation
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.
Results Reference
result

Learn more about this trial

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

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