Inflammation and Insulin Resistance in Rheumatoid Arthritis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Disease Activity Score Based on 28-joint Disease Activity Score (DAS28)
研究概览
简要总结
Rheumatoid arthritis (RA) is a form of arthritis that causes pain, swelling, stiffness, and loss of function in the joints. Over time, joint deformity, joint destruction, and loss of function can occur. Current treatment aims to improve symptoms, but there is no cure for the disease. Pioglitazone is drug that is effective in treating people with diabetes. This study will determine whether pioglitazone can also be used to effectively treat people with RA.
详细描述
RA is an autoimmune disease that causes long-term inflammation of the joints and sometimes other body tissues, too. Recent studies have found that there is an increased prevalence of coronary artery atherosclerosis, metabolic syndrome, and insulin resistance among people with RA. Furthermore, insulin resistance, which can lead to hyperinsulinemia-too much insulin in the blood-has been associated with RA disease activity and the severity of coronary artery atherosclerosis. These correlations suggest that inflammation and hyperinsulinemia somehow interact and facilitate one another.
Pioglitazone is a prescription drug that reduces insulin resistance and is currently used to treat people with diabetes. This study will determine whether pioglitazone can also be used to effectively treat people with RA. Specifically, the study will evaluate the effect of pioglitazone on inflammation, insulin resistance, and atherosclerosis.
Participation in this study will last about 20 weeks. At an initial 1-hour screening, participants will undergo a physical examination, medical history review, blood sampling, and, if female, a urine pregnancy test. Eligible participants will then return for the first of six monthly study visits. At this first visit, participants will be randomly assigned to receive either pioglitazone or placebo, both of which will be taken daily for 8 weeks. This will be followed by a 4-week wash-out period, during which no study treatments will be taken. Then, at Week 12, participants will begin daily treatments of whatever they were not assigned to originally. This second treatment phase will also last for 8 weeks.
All of the study visits will involve the same tests and procedures. The morning before each study visit, participants will collect their urine in a jug, which they will bring to the clinic. Participants will then undergo blood sampling, blood pressure measurements, and artery stiffness measurements. During the study visits at Weeks 4, 8, 16, and 20, participants will be asked to report on their symptoms, pain, and any adverse effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets the American College of Rheumatology (ACR) criteria for the diagnosis of rheumatoid arthritis (RA)
- •Stable disease activity, as evidenced by no change in immunomodulating or anti-inflammatory therapy in the 1 month before study entry
- •Moderate disease activity, as reflected by a minimum of three swollen and tender joints
- •If female of childbearing potential, willing to use effective method of contraception
排除标准
- •Allergic to pioglitazone
- •Active cancer (other than skin cancer)
- •HIV infected
- •Currently receiving dialysis
- •Received an organ or bone marrow transplant
- •Heart failure
- •Severe edema, as judged by the principal investigator
- •Diabetes mellitus requiring drug therapy: levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than twice the upper limit of normal
- •Underwent major surgery in the 3 months before study entry
- •Severe comorbid condition that is likely to compromise survival or study participation
- •Currently receiving gemfibrozil or rifampin
- •Osteoporosis and not receiving osteoporosis medications
- •Unwillingness, or other inability, to cooperate with study procedures
- •Pregnancy
研究组 & 干预措施
Placebo First
Placebo for first 8 weeks, then washout period for 4 weeks, and finally pioglitazone for 8 weeks.
干预措施: Pioglitazone (Drug)
Placebo First
Placebo for first 8 weeks, then washout period for 4 weeks, and finally pioglitazone for 8 weeks.
干预措施: Placebo (Drug)
Pioglitazone First
Pioglitazone for first 8 weeks, then washout period for 4 weeks, and finally placebo for 8 weeks.
干预措施: Pioglitazone (Drug)
Pioglitazone First
Pioglitazone for first 8 weeks, then washout period for 4 weeks, and finally placebo for 8 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Disease Activity Score Based on 28-joint Disease Activity Score (DAS28)
时间窗: Measured after 8 weeks of treatment
A measure of disease activity based upon tender joint count of 28 joints, swollen joint count of 28 joints, erythrocyte sedimentation rate, and global disease activity (GH) as reported by participant. Calculation is as follows: DAS28=0.56\*sqrt(t28) + 0.28\*sqrt(sw28) + 0.70\*Ln(ESR) + 0.014\*GH
Homeostasis Model Assessment (HOMA) for Insulin Sensitivity
时间窗: Measured after 8 weeks of treatment
Homa is a measure of insulin sensitivity, using glucose measured in mmol/L and insulin measured in milliUnits per liter (mU/L) Calculated using the formula Glucose \* Insulin/22/5
次要结局
- C-reactive Protein (CRP)(Measured after 8 weeks of treatment)
- ESR(baseline and after 8 weeks on either placebo or pioglitazone)
研究者
C. Michael Stein
Dan May Professor of Medicine, Professor of Pharmacology, Associate Director of the Division of Clinical Pharmacology
Vanderbilt University