Effect of Probenecid on Synovial Fluid ATP Levels in CPPD
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 21 - 99 |
| Updated: | 3/23/2019 |
| Start Date: | October 15, 2014 |
| End Date: | September 30, 2019 |
| Contact: | Ann K Rosenthal, MD |
| Email: | Ann.Rosenthal@va.gov |
ANK-dependent ATP Efflux Causes Calcium Pyrophosphate Deposition in Cartilage
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.
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.
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.
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.
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
We found this trial at
1
site
Milwaukee, Wisconsin 53295
Principal Investigator: Ann K Rosenthal, MD
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