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Effect of Probenecid on Synovial Fluid ATP Levels in CPPD

Information source: Department of Veterans Affairs
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Calcium Pyrophosphate Deposition Disease

Intervention: Probenecid (Drug)

Phase: Phase 0

Status: Recruiting

Sponsored by: Department of Veterans Affairs

Official(s) and/or principal investigator(s):
Ann K. Rosenthal, MD, Principal Investigator, Affiliation: Clement J. Zablocki VA Medical Center, Milwaukee, WI

Overall contact:
Ann K Rosenthal, MD, Email: Ann.Rosenthal@va.gov


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. We 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.

Clinical Details

Official title: ANK-dependent ATP Efflux Causes Calcium Pyrophosphate Deposition in Cartilage

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: ATP levels in synovial fluid

Detailed description: 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). We 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. We 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 our 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. We will compare differences in ATP and PPi levels in the probenecid treated and the untreated group.


Minimum age: 21 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria: Inclusion criteria:

- Age >21 years,

- CPPD diagnosed by Ryan /McCarty criteria

- Joint effusion in a shoulder or knee

Exclusion Criteria: Exclusion criteria:

- 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

Locations and Contacts

Ann K Rosenthal, MD, Email: Ann.Rosenthal@va.gov

Clement J. Zablocki VA Medical Center, Milwaukee, WI, Milwaukee, Wisconsin 53295-1000, United States; Recruiting
Ann K Rosenthal, MD, Email: Ann.Rosenthal@va.gov
Bambi L Wessel, MLS, Phone: (414) 382-2000, Ext: 46495, Email: bambi.wessel@va.gov
Ann K. Rosenthal, MD, Principal Investigator
Additional Information

Starting date: October 2014
Last updated: April 14, 2015

Page last updated: August 23, 2015

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