Psoriatic ArthritisNCT01123265
National Psoriasis Foundation - Dendritic Cell-Specific Transmembrane Protein (DC-Stamp) Biomarker Study
An observational study of Psoriatic Arthritis, run by University of Rochester at 1 site in United States.
Trial summary
The purpose of this study is to determine whether DC-STAMP, a protein on the surface of osteoclast precursors (OCPs), can be used as a biologic marker in Psoriatic Arthritis (PsA). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Psoriatic Arthritis
- What is being tested?
- Methotrexate and Anti-TNF
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Jun 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Male and female population that are 18 years old and older.
Who may be able to join
- Subject must be >18 years old
- Subject must have >3 tender and swollen joints
- Subject must have must have a target lesion of greater than 3 cm in diameter
- Subjects who meet the the ClASsification of Psoriatic ARthritis (CASPAR) criteria for PsA
- Subjects must have a DC-STAMP pattern III or IV
Who cannot join
- Subjects with active inflammatory synovitis, dactylitis, enthesitis, osteoarthritis, axial disease, Subjects with a SLE, Sjogren's syndrome, scleroderma or inflammatory muscle disease
- Subjects with an active malignancy
- Subjects currently on biologic agents (anti-TNF agents, anti-T or B cells agents) and/or disease-modifying antirheumatic drugs (DMARDs) (methotrexate, leflunomide, hydroxychloroquine, azulfidine, cyclosporine, azathioprine)
- Subjects who have been off DMARDs or biologics for less than 3 months
- Subjects judged ineligible at the discretion of the PI
- Subjects with a history of crystalline arthritis (gout, pseudogout)
Show all 13Show fewer
- Subject pregnancy or breast feeding
- History of recurrent infections - AIM 3 Specific
- Demyelinating disorders - AIM 3 Specific
- Prior non-responsiveness to TNFi - AIM 3 Specific
- Subjects who have a BMI >30 - AIM 3 Specific MTX arm
- Subjects who have a history of type II diabetes - AIM 3 Specific MTX arm
- Subjects with a history of substance abuse including alcohol - AIM 3 Specific MTX arm
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) as a Severity and Response Biomarker in Psoriatic Arthritis
The purpose of this study is to determine whether DC-STAMP, a protein on the surface of osteoclast precursors (OCPs), can be used as a biologic marker in Psoriatic Arthritis (PsA). With this marker the investigators hope to learn more about how OCPs develop as well as find out if DC-STAMP predicts PsA severity and how well treatment works in PsA.
Read the detailed description
Psoriatic Arthritis (PsA), a phenotypically heterogeneous disorder, is characterized by joint damage observed in over half of the patients with early disease. While anti-tumor necrosis factor (TNF) agents have greatly improved signs and symptoms and lessened joint damage, the fact that only a fraction of patients achieve complete remission underscores the tremendous unmet need for this population. To date, a biomarker that can stratify patients by severity and can serve as a leading indicator of treatment response has not been identified.
Our laboratory demonstrated that circulating osteoclast precursors (OCP) are elevated in PsA patients. OCP decline rapidly following anti-TNF therapy and levels are higher in subjects with erosive arthritis compared to those with no x-ray changes. The OCP are derived from CD14+ monocytes and the assay entails culture techniques that are costly, expensive and labor intensive. We developed an antibody (1A2) to Dendritic Cell Specific Transmembrane Protein (DC-STAMP), a potential marker of the OCP population, for analysis by flow cytometry. We found that: 1) the level of monocyte DC-STAMP expression correlated with in vitro osteoclast formation; 2) DC-STAMP expression is significantly elevated in PBMC from PsA subjects compared to controls; 3) TNF dramatically upregulated the expression of DC-STAMP in vitro; 4) DC-STAMP surface expression declined following anti-TNF therapy; 5) subsets of CD3+ cells also express DC-STAMP on the cell membrane. Based on these preliminary data, three hypotheses are proposed:
- DC-STAMP+ CD3+ T cells belong to the Th17 subset which facilitates OC generation;
- DC-STAMP is a marker of disease severity in PsA;
- DC-STAMP is a biomarker of treatment response in PsA.
We propose three Specific Aims to test these hypotheses.
Aim 1 To examine whether DC-STAMP+CD3+ cells belong to the Th17 cell subset, PBMC will be stained with Th17-specific antibodies in PsA subjects with elevated DC-STAMP expression. We will also examine the role of T cells in osteoclastogenesis directly by co-culture experiments and we will use monocyte cultures without added lymphocytes as controls. The expression of DC-STAMP on circulating dendritic cells will be examined ex vivo with 11-color flow cytometry.
Aim 2 To determine if increased DC-STAMP expression is associated with more severe features of PsA, DC-STAMP expression in 40 PsA subjects will be determined and correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
Aim 3 To examine if DC-STAMP is a response marker to anti-TNF treatment, we will recruit 20 PsA patients in Aim 2 with elevated DC-STAMP expression and divide them into 2 groups. Ten subjects will receive methotrexate, and ten will receive anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
- Conditions
- Psoriatic Arthritis
- Being tested
- Methotrexate, Anti-TNF
- Keywords
- PsA, methotrexate, Anti-TNF, TNF, DC-Stamp
- Medical subject headings
- Arthritis, Psoriatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Subjects will start Methotrexate which will be escalated from 7.5 mg weekly to 15 mg/weekly over a 3 week period.
Anti-TNFDrug
Anti-TNF to be administered per standard of care within the practice.
| Study group | Role | What they receive |
|---|---|---|
| Anti-TNF | Not described Receives: Drug: Anti-TNF | |
| Methotrexate | Not described Receives: Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of T cell subset and dendritic cell (DC) subset for DC-STAMP expression
Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
Measured: Week 0 (Baseline)
Analysis of T cell subset and DC subset for DC-STAMP expression
Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
Measured: Week 16
DC-STAMP as a marker of disease severity in PsA
Baseline measurement of DC-STAMP expression will be collected in order to assist in determining whether it is associated with more severe features of PsA. DC-STAMP expression will be correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
Measured: Week 0 (Baseline)
DC-STAMP as a marker of disease severity in PsA
Measurement of DC-STAMP expression will be collected in order to assist in determining whether it is associated with more severe features of PsA. DC-STAMP expression will be correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
Measured: Week 16
DC-STAMP as a biomarker of treatment response in PsA
A baseline measurement of DC-STAMP as a response marker to treatment will be collected. Ten subjects will receive methotrexate and ten will receive anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
Measured: Week 0 (Baseline)
DC-STAMP as a biomarker of treatment response in PsA
A measurement of DC-STAMP as a response marker to treatment will be collected. Ten subjects received methotrexate and ten received anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2010 (estimated)
- Study startJun 2010
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Psoriatic ArthritisStudies of the same condition, open and under way.
- More trials run by University of RochesterThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- National Psoriasis Foundation
- Responsible party
- Principal investigator, Christopher Ritchlin, University of Rochester
- Investigators
- Christopher Ritchlin, MD / MPH, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01123265
- Sponsor's protocol ID
- RSRB - 32368
- Status last verified
- Sep 2015
- First submitted
- 11 May 2010
- Last updated
- 21 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) as a Severity and Response Biomarker in Psoriatic Arthritis
- ClinicalTrials.gov ID
- NCT01123265
- Acronym / sponsor ID
- RSRB - 32368
- Conditions
- Psoriatic Arthritis
- Keywords
- PsA, methotrexate, Anti-TNF, TNF, DC-Stamp
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- National Psoriasis Foundation
- Study start
- Jun 2010
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 14 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether DC-STAMP, a protein on the surface of osteoclast precursors (OCPs), can be used as a biologic marker in Psoriatic Arthritis (PsA). With this marker the investigators hope to learn more about how OCPs develop as well as find out if DC-STAMP predicts PsA severity and how well treatment works in PsA.
Detailed description
Psoriatic Arthritis (PsA), a phenotypically heterogeneous disorder, is characterized by joint damage observed in over half of the patients with early disease. While anti-tumor necrosis factor (TNF) agents have greatly improved signs and symptoms and lessened joint damage, the fact that only a fraction of patients achieve complete remission underscores the tremendous unmet need for this population. To date, a biomarker that can stratify patients by severity and can serve as a leading indicator of treatment response has not been identified.
Our laboratory demonstrated that circulating osteoclast precursors (OCP) are elevated in PsA patients. OCP decline rapidly following anti-TNF therapy and levels are higher in subjects with erosive arthritis compared to those with no x-ray changes. The OCP are derived from CD14+ monocytes and the assay entails culture techniques that are costly, expensive and labor intensive. We developed an antibody (1A2) to Dendritic Cell Specific Transmembrane Protein (DC-STAMP), a potential marker of the OCP population, for analysis by flow cytometry. We found that: 1) the level of monocyte DC-STAMP expression correlated with in vitro osteoclast formation; 2) DC-STAMP expression is significantly elevated in PBMC from PsA subjects compared to controls; 3) TNF dramatically upregulated the expression of DC-STAMP in vitro; 4) DC-STAMP surface expression declined following anti-TNF therapy; 5) subsets of CD3+ cells also express DC-STAMP on the cell membrane. Based on these preliminary data, three hypotheses are proposed:
- DC-STAMP+ CD3+ T cells belong to the Th17 subset which facilitates OC generation;
- DC-STAMP is a marker of disease severity in PsA;
- DC-STAMP is a biomarker of treatment response in PsA.
We propose three Specific Aims to test these hypotheses.
Aim 1 To examine whether DC-STAMP+CD3+ cells belong to the Th17 cell subset, PBMC will be stained with Th17-specific antibodies in PsA subjects with elevated DC-STAMP expression. We will also examine the role of T cells in osteoclastogenesis directly by co-culture experiments and we will use monocyte cultures without added lymphocytes as controls. The expression of DC-STAMP on circulating dendritic cells will be examined ex vivo with 11-color flow cytometry.
Aim 2 To determine if increased DC-STAMP expression is associated with more severe features of PsA, DC-STAMP expression in 40 PsA subjects will be determined and correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
Aim 3 To examine if DC-STAMP is a response marker to anti-TNF treatment, we will recruit 20 PsA patients in Aim 2 with elevated DC-STAMP expression and divide them into 2 groups. Ten subjects will receive methotrexate, and ten will receive anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anti-TNF | – | Drug: Anti-TNF |
| Methotrexate | – | Drug: Methotrexate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Male and female population that are 18 years old and older.
Key inclusion criteria (5 listed)
- Subject must be >18 years old
- Subject must have >3 tender and swollen joints
- Subject must have must have a target lesion of greater than 3 cm in diameter
- Subjects who meet the the ClASsification of Psoriatic ARthritis (CASPAR) criteria for PsA
- Subjects must have a DC-STAMP pattern III or IV
Key exclusion criteria (13 listed)
- Subjects with active inflammatory synovitis, dactylitis, enthesitis, osteoarthritis, axial disease, Subjects with a SLE, Sjogren's syndrome, scleroderma or inflammatory muscle disease
- Subjects with an active malignancy
- Subjects currently on biologic agents (anti-TNF agents, anti-T or B cells agents) and/or disease-modifying antirheumatic drugs (DMARDs) (methotrexate, leflunomide, hydroxychloroquine, azulfidine, cyclosporine, azathioprine)
- Subjects who have been off DMARDs or biologics for less than 3 months
- Subjects judged ineligible at the discretion of the PI
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 |
|---|---|---|
| MethotrexateSubjects will start Methotrexate which will be escalated from 7.5 mg weekly to 15 mg/weekly over a 3 week period. | Drug | Methotrexate |
| Anti-TNFAnti-TNF to be administered per standard of care within the practice. | Drug | Anti-TNF |
Primary outcome
Analysis of T cell subset and dendritic cell (DC) subset for DC-STAMP expression
Time frame: Week 0 (Baseline)
Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
Analysis of T cell subset and DC subset for DC-STAMP expression
Time frame: Week 16
Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
DC-STAMP as a marker of disease severity in PsA
Time frame: Week 0 (Baseline)
Baseline measurement of DC-STAMP expression will be collected in order to assist in determining whether it is associated with more severe features of PsA. DC-STAMP expression will be correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
DC-STAMP as a marker of disease severity in PsA
Time frame: Week 16
Measurement of DC-STAMP expression will be collected in order to assist in determining whether it is associated with more severe features of PsA. DC-STAMP expression will be correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
DC-STAMP as a biomarker of treatment response in PsA
Time frame: Week 0 (Baseline)
A baseline measurement of DC-STAMP as a response marker to treatment will be collected. Ten subjects will receive methotrexate and ten will receive anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
DC-STAMP as a biomarker of treatment response in PsA
Time frame: Week 16
A measurement of DC-STAMP as a response marker to treatment will be collected. Ten subjects received methotrexate and ten received anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2015.
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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.
Christopher Ritchlin, MD / MPH principal investigator
University of Rochester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Psoriatic Arthritis, run by University of Rochester 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 5 inclusion and 13 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 21 Sep 2015. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Analysis of T cell subset and dendritic cell (DC) subset for DC-STAMP expression (time frame: Week 0 (Baseline)). The study lists 6 primary outcomes in all. 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 21 Sep 2015.