- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00798915
Study of the Effects of Xenin-25 in Humans With and Without Type 2 Diabetes Mellitus
April 30, 2018 updated by: Washington University School of Medicine
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.
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
|
Intravenous infusion of 1% human albumin in normal saline
Other Names:
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Names:
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Names:
Intravenous infusion of GIP plus xenin-25 (4 pmoles each x kg-1 x min-1) in 1% human albumin in normal saline
Other Names:
|
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.
|
Intravenous infusion of 1% human albumin in normal saline
Other Names:
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Names:
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Names:
Intravenous infusion of GIP plus xenin-25 (4 pmoles each x kg-1 x min-1) in 1% human albumin in normal saline
Other Names:
|
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.
|
Intravenous infusion of 1% human albumin in normal saline
Other Names:
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Names:
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Names:
Intravenous infusion of GIP plus xenin-25 (4 pmoles each x kg-1 x min-1) in 1% human albumin in normal saline
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The effects of xenin-25 on GIP action in persons with type 2 diabetes
Time Frame: 5yrs
|
5yrs
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Burton Wice, PhD, Washington University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2008
Primary Completion (Actual)
December 1, 2012
Study Completion (Actual)
December 1, 2012
Study Registration Dates
First Submitted
November 24, 2008
First Submitted That Met QC Criteria
November 25, 2008
First Posted (Estimate)
November 26, 2008
Study Record Updates
Last Update Posted (Actual)
May 3, 2018
Last Update Submitted That Met QC Criteria
April 30, 2018
Last Verified
April 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 08-0861A
- 1RC1DK086163-01 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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