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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Probenecid | Experimental | These patients will receive 5 days of probenecid. |
|
| No intervention | No Intervention | These patients will receive no intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Probenecid | Drug | Treatment |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 5 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ann K Rosenthal, MD | Clement J. Zablocki VA Medical Center, Milwaukee, WI | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clement J. Zablocki VA Medical Center, Milwaukee, WI | Milwaukee | Wisconsin | 53295-1000 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Probenecid | These patients will receive 5 days of probenecid. Probenecid: Treatment |
| FG001 | No Intervention | These patients will receive no intervention. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Probenecid | These patients will receive 5 days of probenecid. Probenecid: Treatment |
| BG001 | No Intervention | These patients will receive no intervention. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | nanomoles/ml | 5 days |
|
7 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Probenecid | These patients will receive 5 days of probenecid. Probenecid: Treatment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ann Rosenthal , MD ACOS/Research | Zablocki VA Medical Center | 414-384-2000 | 41430 | ann.rosenthal@va.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 28, 2022 | Mar 24, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 27, 2016 | Mar 24, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D002805 | Chondrocalcinosis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D000070657 | Crystal Arthropathies |
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| ID | Term |
|---|---|
| D011339 | Probenecid |
| D014528 | Uricosuric Agents |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| ATP levels in synovial fluid at day 0 | Mean | Standard Deviation | nanomoles/ml |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 0 |
| 3 |
| EG001 | No Intervention | These patients will receive no intervention. | 0 | 5 | 0 | 5 | 0 | 5 |
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| Sulfur Compounds |
| D006074 | Gout Suppressants |
| D018501 | Antirheumatic Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |