Effect of Probenecid on Synovial Fluid ATP Levels in CPPD

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.

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Key information

Conditions

Calcium Pyrophosphate Deposition Disease Arthritis Chondrocalcinosis Crystal Arthropathies Joint Diseases Musculoskeletal Diseases

Age range

21 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Clement J. Zablocki VA Medical Center, Milwaukee, WI

Milwaukee, Wisconsin, 53295-1000, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Age >21 years,
CPPD diagnosed by Ryan /McCarty criteria
Joint effusion in a shoulder or knee

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

Treatment and study plan

Probenecid

Drug

Treatment

Other names: uricosuric

Primary outcomes

ATP Levels in Synovial Fluid

Time frame: 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.

Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Registry information

Official study title

ANK-dependent ATP Efflux Causes Calcium Pyrophosphate Deposition in Cartilage

Important dates

Study start: 2014
Primary completion: 2021
Study completion: 2021
First posted: Sep 18, 2014
Registry last updated: Jul 26, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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