Effect of Pioglitazone on TIMP-3 and TACE in Type 2 Diabetes (PIO-TACE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT01223196
First received: July 21, 2010
Last updated: May 4, 2012
Last verified: May 2012
  Purpose

Background: Pioglitazone has been shown to have potent anti-inflammatory as well anti-atherosclerotic effects. However, the mechanisms by which pioglitazone exerts these effects are not clear. The investigators propose that tissue inhibitor of metalloproteinase-3 (TIMP-3) and TNF-alfa converting enzyme (TACE) play a major role in pioglitazone mediated improvement in insulin sensitivity and endothelial function. In animal models, low dose pioglitazone inhibits lesion progression and matrix metalloproteinase expression in advanced atherosclerotic plaques. The investigators believe that a lower dose of Pioglitazone will also have anti-inflammatory effects.

Aim: To examine the effect of low dose Pioglitazone (15mg/day) on TIMP and TACE in Pioglitazone mediated improvements in insulin sensitivity.

Methods: Thirty subjects with T2DM will participate in following studies: (i) oral glucose tolerance test (OGTT); (ii) Dual energy absorptiometry(DXA) for body fat content, (iv) skeletal muscle biopsy. Subjects will be randomized to receive either placebo or pioglitazone for 24 weeks. The investigators will study the effect of Pioglitazone on (1) TIMP and TACE substrate activity in skeletal muscle, adipose tissue, mononuclear cells, and their relationship to insulin sensitivity and vascular reactivity, other adipocytokines- resistin, TNF-α and Visfatin; (2) markers of inflammation and atherosclerosis- C-reactive protein, VCAM-1, ICAM-1, endothelin 1, E-selectin, P-selectin, TNFrecI, TNFrecII, IL-6 receptor.


Condition Intervention Phase
Type 2 Diabetes
Drug: Pioglitazone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Effect of Pioglitazone on Tissue Inhibitor of Metalloproteinases (TIMP-3) and TNF-α Converting Enzyme (TACE) in Skeletal Muscle and Their Circulating Substrates

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Effect of Pioglitazone on Tissue Inhibitor of Metalloproteinases (TIMP-3) and TNF alpha converting enzyme (TACE) in skeletal muscle and their circulating substrates [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: August 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
One arm of the study subjects will be treated with Placebo only.
Drug: Pioglitazone
This study will examine the effect of Pioglitazone on tissue inhibitor of metalloproteinases (TIMP-3) and on TNF-alfa converting enzyme in the skeletal muscle of type 2 diabetic subjects.
Other Name: ACTOS
Active Comparator: Pioglitazone
One arm of the study subjects will be treated with Pioglitazone
Drug: Pioglitazone
This study will examine the effect of Pioglitazone on tissue inhibitor of metalloproteinases (TIMP-3) and on TNF-alfa converting enzyme in the skeletal muscle of type 2 diabetic subjects.
Other Name: ACTOS

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Fasting plasma Glucose- 126-270
  • HbA1c <10%
  • Hematocrit >34%
  • Serum creatinine <1.8mg/dl
  • AST < 2times upper limit of normal
  • ALT < 2 time upper limit of normal
  • Alkaline phosphatase <2 times upper limit of normal

Exclusion Criteria:

  • Type 1 DM
  • Fasting plasma glucose >270 mg/dl
  • Thiazolidinedione therapy
  • Insulin therapy in last 3 months
  • Congestive heart failure > NYHA class II
  • History of dyspnoea on exertion
  • Abnormal breath sounds
  • EKG changes other than non-sp ST-T changes or LVH
  • H/O Claudication
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01223196

Locations
United States, Texas
Bartter Research Unit , ALM VA Hospital
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Investigators
Principal Investigator: Franco Folli, MD The University of Texas Health Science Center at San Antonio
  More Information

No publications provided by The University of Texas Health Science Center at San Antonio

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01223196     History of Changes
Other Study ID Numbers: HSC20080452
Study First Received: July 21, 2010
Last Updated: May 4, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center at San Antonio:
Type 2 Diabetes, Thiazolidinediones, TIMP-3, TACE, TNF-a
insulin resistance

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Tissue Inhibitor of Metalloproteinases
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
TIMP1 protein, human
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014