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