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

NCT00798915 | Completed Phase 1 DMC

• 2 other identifiers: 08-0861A1RC1DK086163-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes

Keywords

Diabetes; Blood Sugar; Xenin-25; GIP; Insulin

Outcome Measures

Primary Outcomes (1)

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

  5 years

Secondary Outcomes (1)

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

  5yrs

Study Arms (3)

Normal Glucose Tolerance

EXPERIMENTAL

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

Drug: Placebo; Drug: Glucose-dependent Insulinotropic Polypeptide (GIP); Drug: Xenin-25; Drug: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25

Impaired Glucose Tolerance

EXPERIMENTAL

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

Drug: Placebo; Drug: Glucose-dependent Insulinotropic Polypeptide (GIP); Drug: Xenin-25; Drug: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25

Type 2 diabetes mellitus

EXPERIMENTAL

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.

Drug: Placebo; Drug: Glucose-dependent Insulinotropic Polypeptide (GIP); Drug: Xenin-25; Drug: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25

Interventions

Placebo DRUG

Intravenous infusion of 1% human albumin in normal saline

Also known as: Vehicle alone

Impaired Glucose Tolerance; Normal Glucose Tolerance; Type 2 diabetes mellitus

Glucose-dependent Insulinotropic Polypeptide (GIP) DRUG

Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline

Also known as: GIP

Impaired Glucose Tolerance; Normal Glucose Tolerance; Type 2 diabetes mellitus

Xenin-25 DRUG

Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline

Also known as: Xenin

Impaired Glucose Tolerance; Normal Glucose Tolerance; Type 2 diabetes mellitus

Glucose-dependent Insulinotropic Polypeptide plus Xenin-25 DRUG

Intravenous infusion of GIP plus xenin-25 (4 pmoles each x kg-1 x min-1) in 1% human albumin in normal saline

Also known as: GIP plus Xenin

Impaired Glucose Tolerance; Normal Glucose Tolerance; Type 2 diabetes mellitus

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related 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.2013.10.003. Epub 2013 Oct 29.

  PMID: 24183983 RESULT

• 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.

  PMID: 22522617 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Insulin Resistance

Interventions

Incretins; xenin 25

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Dominic Reeds, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Burton Wice, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2008
• First Posted: November 26, 2008
• Study Start: December 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: May 3, 2018

Record last verified: 2018-04

Locations

US (1)