Calcium Pyrophosphate Deposition Disease
Conditions
Keywords
ATP, Probenecid, Chondrocalcinosis
Brief 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. 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.
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). 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.
Interventions
DRUGProbenecid
Treatment
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ATP Levels in Synovial Fluid | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Probenecid These patients will receive 5 days of probenecid.
Probenecid: Treatment | 3 |
| No Intervention These patients will receive no intervention. | 5 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | no synovial fluid on second aspirate | 0 | 1 |
Baseline characteristics
| Characteristic | Probenecid | No Intervention | Total |
|---|---|---|---|
| Age, Continuous | 77.6 years STANDARD_DEVIATION 12.3 | 68.4 years STANDARD_DEVIATION 10.4 | 71.8 years STANDARD_DEVIATION 11.3 |
| ATP levels in synovial fluid at day 0 | 1.2 nanomoles/ml STANDARD_DEVIATION 0.9 | 4.5 nanomoles/ml STANDARD_DEVIATION 6.7 | 2.85 nanomoles/ml STANDARD_DEVIATION 2.33 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 8 Participants |
| Region of Enrollment United States | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 0 / 3 | 0 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 5 |
Outcome results
Primary
ATP Levels in Synovial Fluid
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.
Time frame: 5 days
Population: Two subjects ( one in probenecid and one in no intervention group) had no measurable ATP on the second aspirate, and one subject in the no intervention group did not have any synovial fluid on the second visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Probenecid | ATP Levels in Synovial Fluid | 4.4 nanomoles/ml | Standard Deviation 2.5 |
| no Intervention | ATP Levels in Synovial Fluid | 31.4 nanomoles/ml | Standard Deviation 56.6 |