Effect of Pioglitazone on Oxidative Load, Inflammatory End-Points and Vascular Reactivity in Obese Non-Diabetic Patients: A Dose Ranging Study
|Inflammation||Drug: Pioglitazone 15mg Drug: pioglitazone 30mg Drug: placebo||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effect of Pioglitazone on Oxidative Load, Inflammatory End-Points and Vascular Reactivity in Obese Non-Diabetic Patients: A Dose Ranging Study|
- Inflammation [ Time Frame: 12 weeks ]Percent change in NFkb at baseline and after 1, 2, 4, 6, and 12 weeks of pioglitazone therapy.
- inflammation [ Time Frame: 12 weeks ]TBARS (Thiobarbituric acid reactive substances), ortho and meta-tyrosine, 9-HODE and 13-HODE (hydroxyoctadecadieonic acid derivatives), Cellular/nuclear fractions and DNA binding activity of Nuclear Factor kb, Ikb (inhibitory kappa B), TNF-a(Tumor necrosis factor a), ICAM-1 (Intracellular adhesion molecule 1), VCAM-1(Vascular adhesion molecule 1), PAI-1 (Plasminogen Activator Inhibitor -1) and CRP (C-Reactive protein) and %change in vascular reactivity.
|Study Completion Date:||October 2003|
Experimental: Pioglitazone 15mg
8 patient will receive this drug
|Drug: Pioglitazone 15mg|
Experimental: pioglitazone 30mg
8 patients will get this drug
|Drug: pioglitazone 30mg|
Placebo Comparator: Placebo
8 patient will get this drug
This is a single center, open labeled study. A total of 24 obese patients will be recruited to participate in this study. The study will have three groups of 8 patients each. Subjects will be enrolled into each group by alternate recruitment. Subjects in group one will receive 15mg of pioglitazone; subjects in group two will receive 30 mg of pioglitazone; subjects in group three will receive placebo. All subjects will receive Pioglitazone or placebo for 6 weeks, followed by a 6-week observation period off Pioglitazone/placebo.
At baseline, and at week 1, week 2, week 4, week 6 and month 3 all patients will have blood drawn for TBARS, ortho and meta-tyrosine, 9-HODE and 13-HODE, NF, Ikb, TNF-a, ICAM-1, VCAM-1, PAI-1, AP-1, EGR-1, MMP-2, MMP-9, TIMP, CRP-1, E-Selectin, P-Selectin, Asymmetric dimethylarginine (ADMA), PAPP-A, SAA, MCP-1, IL-6, ROS generation, insulin levels, and CRP.
Post-ischemic dilation of the brachial artery will be used as an index of endothelium-mediated vasodilation. All subjects will have an oral glucose tolerance test (GTT) with 75gm of glucose at Day 0 and at Day 42. Vascular reactivity will be assessed at 0, 6, and at 12 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01161394
|United States, New York|
|Millard Fillmore gates Hospital|
|Buffalo, New York, United States, 14226|
|Principal Investigator:||Paresh Dandona, MD||Kaleida Health|