ANK-dependent ATP Efflux Causes Calcium Pyrophosphate Deposition in Cartilage
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- ATP Levels in Synovial Fluid
研究概览
简要总结
This study will investigate the hypothesis that probenecid, a medication currently used for gout, reduces levels of ATP in the joint fluid of patients with calcium pyrophosphate deposition disease (CPPD), another common type of crystal-related arthritis. There is good evidence that CPPD results from an excess of ATP in joints. The investigators will measure levels of ATP in joint fluid before and after 5 days of treatment with probenecid. This study will serve to rationalize larger studies of probenecid in CPPD.
详细描述
Objective
The objective of this study is to determine whether pharmacologic doses of the drug probenecid significantly decrease ATP and inorganic pyrophosphate (PPi) levels in the synovial fluid of patients with calcium pyrophosphate deposition disease (CPPD). The investigators have considerable evidence that synovial fluid ATP levels are high in patients with this disease and these high levels lead to calcium pyrophosphate (CPP) crystal formation which then produces acute and chronic arthritis. The investigators have identified the transmembrane protein known as ANK as the chief regulator of ATP levels in and around cartilage. Probenecid blocks function of ANK in vitro. The purpose of this study is to determine if probenecid used at normal doses are sufficient to block ANK function in vivo and whether this results in reduced ATP and PPi levels in synovial fluid.
Research design: This is a randomized un-controlled trial of probenecid vs. no drug in patients with a joint effusion and known CPPD.
Methodology: Power analysis based on an 80% chance to show a 20% difference in ATP levels in the treatment group resulted in a sample size of 20 patients in each group. Patients with known CPPD and a joint effusion will have an arthrocentesis to remove 2 ml of synovial fluid from their joint. Fluid will be sent to the investigators' research laboratory and ATP and PPi levels will be measured. Patients will be randomized to treatment with 2 grams/day of probenecid or no therapy. After 5 days, the remainder of the joint fluid will be removed and tested for ATP and PPi levels. The investigators will compare differences in ATP and PPi levels in the probenecid treated and the untreated group.
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
- 21 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >21 years,
- •CPPD diagnosed by Ryan /McCarty criteria
- •Joint effusion in a shoulder or knee
排除标准
- •Inability to sign informed consent
- •Age <21 years
- •History of renal stones
- •Significant renal dysfunction (CKD >stage 2)
- •Blood dyscrasias
- •Current use of drugs which interact with probenecid
- •Concurrent gout
- •Active infection, including bacteremia and overlying cellulitis
- •Recent joint trauma
- •Intra-articular corticosteroids in the affected joint within three months
研究组 & 干预措施
Probenecid
These patients will receive 5 days of probenecid.
干预措施: Probenecid (Drug)
结局指标
主要结局
ATP Levels in Synovial Fluid
时间窗: 5 days
The investigators will measure levels of ATP in synovial fluid from patients with CPPD before and after treatment with probenecid compared to patients receiving no therapy. ATP levels are measured with a standard bioluminescent assay.
次要结局
未报告次要终点