Effect of Pioglitazone on Oxidative Load, Inflammatory End-Points and Vascular Reactivity in Obese Non-Diabetic Patients: A Dose Ranging Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Inflammation
研究概览
简要总结
Pioglitazone decreases oxidative load, inflammatory end points and improves vascular reactivity in obese patients in a dose dependent manner and that this effect is independent of its glucose lowering effects.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •• Obese (BMI>=30)
- •Age: 20 to 65 years of age inclusive
- •Without established clinical coronary artery disease (documented history or myocardial infarction, typical angina and an exercise ECG positive for ischemia or angiographic evidence of CAD)
- •Good health as evidence by History and Physical exam
- •Female subjects must be:
- •Postmenopausal for at least one year or Surgically incapable of childbearing (i.e. have had a hysterectomy or tubal ligation) or, if capable of childbearing a subject, must be practicing an acceptable method of contraception.
- •Subject will be available for duration of the study and willing to comply with all study requirements.
排除标准
- •• Diabetes Mellitus
- •Allergy or sensitivity to Pioglitazone
- •Current use of Insulin therapy.
- •Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks
- •Hepatic disease (transaminase > 3 times normal)
- •Renal impairment (Creatinine clearance < 50 mL/min)
- •History of drug or alcohol abuse
- •Participation in any other concurrent clinical trial
- •Any other life-threatening, non-cardiac disease
- •Use of an investigational agent or therapeutic regimen within 30 days of study
- •Pregnancy or nursing
研究组 & 干预措施
Pioglitazone 15mg
8 patient will receive this drug
干预措施: Pioglitazone 15mg (Drug)
pioglitazone 30mg
8 patients will get this drug
干预措施: pioglitazone 30mg (Drug)
Placebo
8 patient will get this drug
干预措施: placebo (Drug)
结局指标
主要结局
Inflammation
时间窗: 12 weeks
Percent change in NFkb at baseline and after 1, 2, 4, 6, and 12 weeks of pioglitazone therapy.
次要结局
- inflammation(12 weeks)
研究者
Paresh Dandona
Principal Investigator
University at Buffalo