- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02243631
Effect of Probenecid on Synovial Fluid ATP Levels in CPPD
ANK-dependent ATP Efflux Causes Calcium Pyrophosphate Deposition in Cartilage
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Wisconsin
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Milwaukee, Wisconsin, United States, 53295-1000
- Clement J. Zablocki VA Medical Center, Milwaukee, WI
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Probenecid
These patients will receive 5 days of probenecid.
|
Treatment
Other Names:
|
No Intervention: No intervention
These patients will receive no intervention.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
5 days
|
Collaborators and Investigators
Investigators
- Principal Investigator: Ann K Rosenthal, MD, Clement J. Zablocki VA Medical Center, Milwaukee, WI
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IMMA-022-13F
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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