Phase 4 Completed N=24 Randomized Double-blind

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

Source: ClinicalTrials.gov NCT01223196 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Nov 2014

Primary outcomePrimary: Whole Body Insulin Sensitivity During the Euglycemic Insulin Clamp — 3.2; 3.01; 3.4; 3.7 Mg. of glucose/kg body w./mUxl ins. — p=0.04

Summary

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 (vascular cell adhesion molecule 1), ICAM-1 (Intercellular Adhesion Molecule 1), endothelin 1, E-selectin, P-selectin, TNFrecI (Tumor Necrosis Factor Receptor I), TNFrecII (Tumor Necrosis Factor Receptor II), IL-6 (Interleukin 6) receptor.

Outcome Measures

Outcome	Result	p-value
PRIMARY Whole Body Insulin Sensitivity During the Euglycemic Insulin Clamp	3.2; 3.01; 3.4; 3.7	0.04 sig
SECONDARY Effect of Pioglitazone on TNF (Tumor Necrosis Factor) Alpha Converting Enzyme (TACE) Activity in Skeletal Muscle.	0.2; 0.28; 0.15; 0.06	<0.05 sig

Eligibility Criteria

Inclusion Criteria

Fasting plasma Glucose- 126-270
HbA1c 34%
Serum creatinine 270 mg/dl
Thiazolidinedione therapy
Insulin therapy in last 3 months
Congestive heart failure > NYHA (New York Heart Association) class II
History of dyspnoea on exertion
Abnormal breath sounds
EKG changes other than non-specific ST-T changes in the ECG (Electro-CardioGram) or LVH (Left Ventricular Hypertrophy)
H/O Claudication

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01223196). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.