Study of the Effects of Xenin-25 in Humans With and Without Type 2 Diabetes Mellitus
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:
NCT00798915
First received: November 24, 2008
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 |
|---|---|---|
|
Diabetes |
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: | Restoration of the GIP-mediated Incretin Effect in Persons With Type 2 Diabetes Mellitus |
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: 5 years ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- The effects of xenin-25 on GIP action in persons with type 2 diabetes [ Time Frame: 5yrs ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 40 |
| Study Start Date: | December 2008 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | December 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 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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00798915
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: | Dominic Reeds, MD | Washington University School of Medicine |
| Principal Investigator: | Burton Wice, PhD | Washington University School of Medicine |
More Information
No publications provided by Washington University School of Medicine
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Washington University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT00798915 History of Changes |
| Other Study ID Numbers: | 08-0861A, 1RC1DK086163-01 |
| Study First Received: | November 24, 2008 |
| 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 Incretins |
Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Gastrointestinal Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on June 17, 2013