Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function
This study is ongoing, but not recruiting participants.
Sponsor:
Washington University School of Medicine
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00949663
First received: July 28, 2009
Last updated: February 9, 2012
Last verified: February 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Type 2 Diabetes Mellitus |
Drug: Placebo Drug: Glucose-dependent Insulinotropic Polypeptide (GIP) Drug: Xenin-25 Drug: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25 |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment |
| Official Title: | Xenin-25: Novel Regulator of Insulin Secretion and Beta-cell Function |
Resource links provided by NLM:
Further study details as provided by Washington University School of Medicine:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: Yes ]
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. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 40 |
| Study Start Date: | October 2009 |
| Estimated Study Completion Date: | June 2013 |
| Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
|
Drug: Placebo
Intravenous infusion of 1% human albumin in normal saline
Other Name: Vehicle Alone
Drug: Glucose-dependent Insulinotropic Polypeptide (GIP)
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Name: GIP
Drug: Xenin-25
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Name: Xenin
Drug: 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
Other Name: GIP plus Xenin
|
|
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.
|
Drug: Placebo
Intravenous infusion of 1% human albumin in normal saline
Other Name: Vehicle Alone
Drug: Glucose-dependent Insulinotropic Polypeptide (GIP)
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Name: GIP
Drug: Xenin-25
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Name: Xenin
Drug: 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
Other Name: GIP plus Xenin
|
|
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.
|
Drug: Placebo
Intravenous infusion of 1% human albumin in normal saline
Other Name: Vehicle Alone
Drug: Glucose-dependent Insulinotropic Polypeptide (GIP)
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Name: GIP
Drug: Xenin-25
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Other Name: Xenin
Drug: 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
Other Name: GIP plus Xenin
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00949663
Locations
| United States, Missouri | |
| Washington University School of Medicine | |
| St. Louis, Missouri, United States, 63110 | |
Sponsors and Collaborators
Washington University School of Medicine
Investigators
| Principal Investigator: | Burton Wice, PhD | Washington University School of Medicine |
| Principal Investigator: | Dominic Reeds, MD | Washington University School of Medicine |
More Information
No publications provided
| Responsible Party: | Washington University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT00949663 History of Changes |
| Other Study ID Numbers: | 08-0861B, 1R01DK088126-01 |
| Study First Received: | July 28, 2009 |
| Last Updated: | February 9, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Washington University School of Medicine:
|
Diabetes Blood Sugar Xenin-25 GIP Insulin |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Gastric Inhibitory Polypeptide Insulin Incretins |
Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Gastrointestinal Agents Therapeutic Uses Hypoglycemic Agents |
ClinicalTrials.gov processed this record on May 16, 2013