Calcium Pyrophosphate Deposition DiseaseEarly Phase 1NCT02243631
Effect of Probenecid on Synovial Fluid ATP Levels in CPPD
A Early Phase 1 study testing Probenecid in people with Calcium Pyrophosphate Deposition Disease, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Calcium Pyrophosphate Deposition Disease
- What is being tested?
- Probenecid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2014to 8 Apr 2021
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >21 years,
- CPPD diagnosed by Ryan /McCarty criteria
- Joint effusion in a shoulder or knee
Who cannot join
- 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
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- Concurrent gout
- Active infection, including bacteremia and overlying cellulitis
- Recent joint trauma
- Intra-articular corticosteroids in the affected joint within three months
Trial locations and contacts
1 site in 1 country.
United States1 site
Clement J. Zablocki VA Medical Center, Milwaukee, WI
Milwaukee, Wisconsin, 53295-1000
About this study
Official title: 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.
Read the 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.
- Conditions
- Calcium Pyrophosphate Deposition Disease
- Being tested
- Probenecid
- Keywords
- ATP, Probenecid, Chondrocalcinosis
- Medical subject headings
- Chondrocalcinosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbenecidDrug
Also called uricosuric
Treatment
| Study group | Role | What they receive |
|---|---|---|
| Probenecid | Experimental | These patients will receive 5 days of probenecid. Receives: Drug: Probenecid |
| No intervention | No intervention | These patients will receive no intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2014 (estimated)
- Study start15 Oct 2014
- Primary completion8 Apr 2021
- Study completion8 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Calcium Pyrophosphate Deposition DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Ann K Rosenthal, MD, Principal investigator, Clement J. Zablocki VA Medical Center, Milwaukee, WI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02243631
- Sponsor's protocol ID
- IMMA-022-13F
- Status last verified
- Jul 2022
- First submitted
- 16 Sep 2014
- Last updated
- 26 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ANK-dependent ATP Efflux Causes Calcium Pyrophosphate Deposition in Cartilage
- ClinicalTrials.gov ID
- NCT02243631
- Acronym / sponsor ID
- IMMA-022-13F
- Conditions
- Calcium Pyrophosphate Deposition Disease
- Keywords
- ATP, Probenecid, Chondrocalcinosis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 15 Oct 2014 (actual)
- Primary completion
- 8 Apr 2021 (actual)
- Study completion
- 8 Apr 2021 (actual)
- First posted
- 18 Sep 2014 (estimated)
- Results
- Posted 26 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probenecid | Experimental | Drug: ProbenecidThese patients will receive 5 days of probenecid. |
| No intervention | No intervention | –These patients will receive no intervention. |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age >21 years,
- CPPD diagnosed by Ryan /McCarty criteria
- Joint effusion in a shoulder or knee
Key exclusion criteria (10 listed)
- Inability to sign informed consent
- Age <21 years
- History of renal stones
- Significant renal dysfunction (CKD >stage 2)
- Blood dyscrasias
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProbenecidAlso: uricosuricTreatment | Drug | Probenecid |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ann K Rosenthal, MD principal investigator
Clement J. Zablocki VA Medical Center, Milwaukee, WI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Probenecid in people with Calcium Pyrophosphate Deposition Disease, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ATP Levels in Synovial Fluid (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2022.