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

Primary Purpose

Type 2 Diabetes Mellitus

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

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus 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:

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.

Exclusion Criteria:

<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.

Sites / Locations

Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

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

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.

Full Information

NCT ID

NCT00949663

First Posted

July 28, 2009

Last Updated

July 21, 2014

Sponsor

Washington University School of Medicine

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT00949663

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2014

Overall Recruitment Status

Completed

Study Start Date

October 2009 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

February 2014 (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 meal tolerance test (MTT) on 4 separate occasions. For the MTT, a liquid meal (Boost Plus)will be ingested following an overnight fast. 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 meal is ingested. Blood samples will be collected before and during the MTT 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

Type 2 Diabetes Mellitus

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

38 (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

3 years

Secondary Outcome Measure Information:

Title

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.

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: <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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Burton Wice, PhD

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Dominic Reeds, MD

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24356886

Citation

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.

Results Reference

derived

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

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