Pioglitazone Incretin Study - Full Text View

Sponsor:	University of Vermont
Collaborator:	Takeda Global Research & Development Center, Inc.
Information provided by:	University of Vermont
ClinicalTrials.gov Identifier:	NCT00656864

Purpose

Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar). In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. This helps the body to metabolize the glucose more effectively, lowering blood sugar levels. GLP-1 and GIP do not work as well in patients with type 2 diabetes (T2DM) as in subjects who do not have diabetes. This study tests whether a medicine called pioglitazone (Actos), which is commonly used to treat T2DM, improves the ability of GIP to increase insulin secretion.

To address this question the investigators will recruit patients with T2DM whose diabetes is controlled with either diet and exercise or with metformin (another medicine commonly used to treat T2DM). Subjects will undergo measurement of body fat by DEXA scanning and a series of studies to characterize their metabolism. These studies include an oral glucose tolerance test (a test sometimes used to diagnose diabetes), a mixed-meal challenge (to measure how much GLP-1 and GIP are produced in response to a meal) and measurement of insulin secretion in response to glucose and GIP given through a vein. The investigators will also obtain small samples of fat (from just under the skin of the belly) using a needle to measure levels of the receptor for GIP. Subjects will then be randomly assigned to 12 weeks of treatment with either pioglitazone or matching placebo (an inactive tablet that does not contain medication). The dose of pioglitazone will be increased during the first 4 weeks to the maximum prescribed dose of 45 mg per day. Subjects will be seen every 2-4 weeks during the treatment phase of the study. After 12 weeks of treatment all studies performed at the beginning of the study will be repeated. The pioglitazone treatment will continue until the end of testing, approximately 4 weeks.

The results of this study may give us information about why glucose control deteriorates in T2DM. This information might also lead to new ways to prevent or treat T2DM.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: Pioglitazone Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Basic Science
Official Title:	Effects of Pioglitazone on the Regulation of Insulin Secretion in Patients With Type 2 Diabetes

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

Further study details as provided by University of Vermont:

Primary Outcome Measures:

Change in incretin-mediated insulin secretion and receptor regulation of glucose-dependent insulinotropic peptide (GIP) in patients with type 2 diabetes. [ Time Frame: 12 weeks per subject ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in active GIP in response to an oral glucose tolerance test and mixed meal challenge [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in active GLP-1 in response to the oral glucose tolerance test and the mixed meal challenge [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in glucose response during the oral glucose tolerance test and mixed meal challenge [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in insulin secretion during the oral glucose tolerance test and the mixed meal challenge [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in the acute insulin response to glucose, insulin sensitivity and the disposition index during the IV glucose tolerance test. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in adipocyte GIP receptor mRNA expression levels. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	May 2008
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Pioglitazone arm	Drug: Pioglitazone Starting dose at 15 mg for two weeks, then titrated up to 45 mg in the subsequent 2 weeks. Other Name: Actos (brand name for pioglitazone)
Placebo Comparator: 2 Placebo arm	Drug: Placebo placebo

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Type 2 diabetes controlled with diet+exercise or metformin monotherapy
HbA1c less than or equal to 7%
Women will be non-fertile or practicing birth control

Exclusion Criteria:

Acute or chronic medical conditions that would contraindicate participation
Class III or IV heart failure
Pregnant or nursing women
Patients taking antidiabetic medications other than metformin, oral or chronic topical steroids, weight loss agents, antipsychotics, or other drugs that could affect insulin sensitivity or secretion.
AST or ALT more than 2.5 times the upper limit of normal
Active alcohol or drug abuse
Weight greater than 300 pounds

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00656864

Locations

United States, Vermont
University of Vermont
South Burlington, Vermont, United States, 05403

Sponsors and Collaborators

University of Vermont

Takeda Global Research & Development Center, Inc.

Investigators

Principal Investigator:

Richard E Pratley, MD

University of Vermont

More Information

No publications provided

Responsible Party:	Richard Pratley, MD, University of Vermont College of Medicine
ClinicalTrials.gov Identifier:	NCT00656864 History of Changes
Other Study ID Numbers:	08-107, GCRC-962
Study First Received:	April 7, 2008
Last Updated:	February 1, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Vermont:

Diabetes
pioglitazone
GIP

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012