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

NCT00949663 | Completed Phase 1 DMC

• 2 other identifiers: 08-0861B1R01DK088126-01
• Study Type: interventional
• Target: 38
• 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

Type 2 Diabetes Mellitus

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

  3 years

Secondary Outcomes (1)

• 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.

  3 years

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:

• 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.

You may not qualify if:

• \<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.

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 (1)

• 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.

  PMID: 24356886 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; 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

• Burton Wice, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Dominic Reeds, MD

  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: July 28, 2009
• First Posted: July 30, 2009
• Study Start: October 1, 2009
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: July 22, 2014

Record last verified: 2014-07

Locations

US (1)