NCT00656864

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for phase_4 diabetes-mellitus-type-2

Timeline
Completed

Started May 2008

Typical duration for phase_4 diabetes-mellitus-type-2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 7, 2008

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 11, 2008

Completed
20 days until next milestone

Study Start

First participant enrolled

May 1, 2008

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2010

Completed
Last Updated

February 2, 2011

Status Verified

January 1, 2010

Enrollment Period

2.5 years

First QC Date

April 7, 2008

Last Update Submit

February 1, 2011

Conditions

Diabetes Mellitus, Type 2

Keywords

DiabetespioglitazoneGIP

Outcome Measures

Primary Outcomes (1)

  • Change in incretin-mediated insulin secretion and receptor regulation of glucose-dependent insulinotropic peptide (GIP) in patients with type 2 diabetes.

    12 weeks per subject

Secondary Outcomes (6)

  • Change in active GIP in response to an oral glucose tolerance test and mixed meal challenge

    12 weeks

  • Change in active GLP-1 in response to the oral glucose tolerance test and the mixed meal challenge

    12 weeks

  • Change in glucose response during the oral glucose tolerance test and mixed meal challenge

    12 weeks

  • Change in insulin secretion during the oral glucose tolerance test and the mixed meal challenge

    12 weeks

  • Change in the acute insulin response to glucose, insulin sensitivity and the disposition index during the IV glucose tolerance test.

    12 weeks

  • +1 more secondary outcomes

Study Arms (2)

1

ACTIVE COMPARATOR

Pioglitazone arm

Drug: Pioglitazone

2

PLACEBO COMPARATOR

Placebo arm

Drug: Placebo

Interventions

PioglitazoneDRUG

Starting dose at 15 mg for two weeks, then titrated up to 45 mg in the subsequent 2 weeks.

Also known as: Actos (brand name for pioglitazone)
1
PlaceboDRUG

placebo

2

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Vermont

South Burlington, Vermont, 05403, United States

Location

Related Publications (3)

  • Nunez Lopez YO, Casu A, Kovacova Z, Petrilli AM, Sideleva O, Tharp WG, Pratley RE. Coordinated regulation of gene expression and microRNA changes in adipose tissue and circulating extracellular vesicles in response to pioglitazone treatment in humans with type 2 diabetes. Front Endocrinol (Lausanne). 2022 Aug 31;13:955593. doi: 10.3389/fendo.2022.955593. eCollection 2022.

    PMID: 36120427DERIVED

  • Tharp WG, Gupta D, Sideleva O, Deacon CF, Holst JJ, Elahi D, Pratley RE. Effects of Pioglitazone on Glucose-Dependent Insulinotropic Polypeptide-Mediated Insulin Secretion and Adipocyte Receptor Expression in Patients With Type 2 Diabetes. Diabetes. 2020 Feb;69(2):146-157. doi: 10.2337/db18-1163. Epub 2019 Nov 22.

    PMID: 31757794DERIVED

  • Kovacova Z, Tharp WG, Liu D, Wei W, Xie H, Collins S, Pratley RE. Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes. Obesity (Silver Spring). 2016 Apr;24(4):820-8. doi: 10.1002/oby.21418. Epub 2016 Feb 17.

    PMID: 26887289DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetes Mellitus

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

ThiazolidinedionesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Richard E Pratley, MD

    University of Vermont

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

April 7, 2008

First Posted

April 11, 2008

Study Start

May 1, 2008

Primary Completion

November 1, 2010

Study Completion

November 1, 2010

Last Updated

February 2, 2011

Record last verified: 2010-01

Locations

US(1)