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

Diabetes Clinical Trial

Official title:

Restoration of the GIP-mediated Incretin Effect in Persons With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00798915
• Other study ID #: 08-0861A
• Secondary ID: 1RC1DK086163-01
• Status: Completed
• Phase: Phase 1
• Start date: December 2008
• Est. completion date: December 2012

Study information

• Verified date: April 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Placebo
Intravenous infusion of 1% human albumin in normal saline
• Glucose-dependent Insulinotropic Polypeptide (GIP)
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
• Xenin-25
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
• 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

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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.20 — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The effects of GIP, xenin-25, or a combination of GIP plus xenin-25 on insulin secretion and blood glucose levels		5 years
Secondary	The effects of xenin-25 on GIP action in persons with type 2 diabetes		5yrs