Rheumatoid ArthritisNCT05754112
JAK-i on RA B-lymphocytes Tolerance and Disease Resolution Through JAK Signaling In Rheumatoid Arthritis
An observational study of Rheumatoid Arthritis, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
The study will reveal the transcriptomic signature linked to the aberrant activation of B lymphocytes in RA identifying novel molecular potential targets for inflammation resolution and immune tolerance promotion. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- B lymphocyte profiling
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 29 Jul 2021to 31 Dec 2023
- 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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: This is an interventional research without experimental drug which will be performed at the Division of Clinical Immunology of the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, Italy, where patients with Rheumatoid Arthritis will undergo to synovial tissue inflammation assessment through minimally invasive US-guided synovial tissue biopsy.
Who may be able to join
- Signed Written Informed Consent. Before any study procedures are performed,subjects will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of trained study personnel.
- Patients fulfilling classification criteria for Rheumatoid Arthritis (2010 ACR/EULARclassification criteria)
- Age: 18-70 years
- For preclinical cohort: Individuals with positivity for ACPA or IgM/IgA RF without clinical signs of arthritis, whose positivity is not related to other concomitant pathologic conditions.
- For naive to treatment cohort: RA patients without previous exposure to conventional DMARDs or biologic/targeted synthetic-DMARDs.
- For resistant to treatment cohort: RA patients with failure to previous conventionalDMARDs for inadequate response or side effects.
- For remission RA cohort: RA patients in sustained clinical and ultrasound remission as stated in section 3.3.1.
- For healthy control cohort: Healthy donors will be aged from 18 to 70 years.
Who cannot join
- Severe and uncontrolled infections such as sepsis and opportunistic infections.
- Patients who are currently included in any interventional clinical trial in RA.
- RA patients in therapy with other biologics.
- Healthy donors receiving anti-inflammatory drugs
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Division of Clinical Immunology, Fondazione Policlinico Universitario A. Gemelli-IRCCS
Rome, 00168
Elisa Gremese, Prof., 00390630159659, elisa.gremese@policlinicogemelli.it
About this study
Official title: Dissecting the Role of B Lymphocytes in the Loss of Immunological Tolerance and Disease Resolution Through JAK Signaling In Rheumatoid Arthritis
The study will reveal the transcriptomic signature linked to the aberrant activation of B lymphocytes in RA identifying novel molecular potential targets for inflammation resolution and immune tolerance promotion. The combination with B lymphocytes phenotyping will dissect the impact of the identified genes on B lymphocyte maturation and activation in RA. Moreover, in vitro study on B lymphocyte cultures using selective JAK1 inhibition will reveal, at deeper level, its transcriptomic effect on RA B lymphocytes activation profile and phenotype, providing the discovery of new biomarkers of the loss of immunological tolerance, active disease and long lasting disease remission.
- Conditions
- Rheumatoid Arthritis
- Being tested
- B lymphocyte profiling
- Keywords
- rheumatoid arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
B lymphocyte profilingOther
All individuals will undergo peripheral venous blood sampling and ultrasound-guided synovial tissue biopsy following a standardized procedure. B-lymphocytes will be sorted from PBMCs isolated by Ficoll gradient method using magnetic CD19-microbeads whereas tissue B-lymphocytes will be isolated from synovial tissue biopsies digested with Liberase. CD19 positive cells from PBMC will be incubated with pro-inflammatory molecules in presence or absence of Ubadacitinib. After stimulation, CD19 positive cells will be collected and processed for single cell RNA sequencing. Moreover, the impact of JAK-1 selective inhibition on B-lymphocyte cultures stimulation will be tested using ELISA method for the assessment of cytokines/chemokines production. Synovial tissue and synovial tissue B-lymphocyte subpopulations will be assessed through FACS analysis using IgD/CD27 classification. Finally, we will compare the transcriptomic profile of synovial tissue B lymphocytes from 5 subject groups.
| Study group | Role | What they receive |
|---|---|---|
| ACPA/RFpos asyntomatic individuals | ACPA and/or RF positive individuals without active arthritis Receives: Other: B lymphocyte profiling | |
| Naive Active RA | Treatment-naive active RA (disease duration<1 year) Receives: Other: B lymphocyte profiling | |
| Resistant RA | Active despite treatment RA Receives: Other: B lymphocyte profiling | |
| Remission RA | RA in sustained clinical and ultrasound remission Receives: Other: B lymphocyte profiling | |
| Control Group | Individuals asymptomatic for joint inflammation without ACPA/RF positivity Receives: Other: B lymphocyte profiling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peripheral blood and synovial tissue B lymphocyte atlas
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2023
- Study start29 Jul 2021
- Primary completion2 May 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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
- Cross-sectional
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gremese Elisa, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05754112
- Sponsor's protocol ID
- 4109
- Status last verified
- Feb 2023
- First submitted
- 22 Feb 2023
- Last updated
- 3 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dissecting the Role of B Lymphocytes in the Loss of Immunological Tolerance and Disease Resolution Through JAK Signaling In Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT05754112
- Acronym / sponsor ID
- 4109
- Conditions
- Rheumatoid Arthritis
- Keywords
- rheumatoid arthritis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 29 Jul 2021 (actual)
- Primary completion
- 2 May 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 3 Mar 2023 (actual)
- 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 study will reveal the transcriptomic signature linked to the aberrant activation of B lymphocytes in RA identifying novel molecular potential targets for inflammation resolution and immune tolerance promotion. The combination with B lymphocytes phenotyping will dissect the impact of the identified genes on B lymphocyte maturation and activation in RA. Moreover, in vitro study on B lymphocyte cultures using selective JAK1 inhibition will reveal, at deeper level, its transcriptomic effect on RA B lymphocytes activation profile and phenotype, providing the discovery of new biomarkers of the loss of immunological tolerance, active disease and long lasting disease remission.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| ACPA/RFpos asyntomatic individuals | – | Other: B lymphocyte profilingACPA and/or RF positive individuals without active arthritis |
| Naive Active RA | – | Other: B lymphocyte profilingTreatment-naive active RA (disease duration<1 year) |
| Resistant RA | – | Other: B lymphocyte profilingActive despite treatment RA |
| Remission RA | – | Other: B lymphocyte profilingRA in sustained clinical and ultrasound remission |
| Control Group | – | Other: B lymphocyte profilingIndividuals asymptomatic for joint inflammation without ACPA/RF positivity |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This is an interventional research without experimental drug which will be performed at the Division of Clinical Immunology of the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, Italy, where patients with Rheumatoid Arthritis will undergo to synovial tissue inflammation assessment through minimally invasive US-guided synovial tissue biopsy.
Key inclusion criteria (8 listed)
- Signed Written Informed Consent. Before any study procedures are performed,subjects will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of trained study personnel.
- Patients fulfilling classification criteria for Rheumatoid Arthritis (2010 ACR/EULARclassification criteria)
- Age: 18-70 years
- For preclinical cohort: Individuals with positivity for ACPA or IgM/IgA RF without clinical signs of arthritis, whose positivity is not related to other concomitant pathologic conditions.
- For naive to treatment cohort: RA patients without previous exposure to conventional DMARDs or biologic/targeted synthetic-DMARDs.
Key exclusion criteria (4 listed)
- Severe and uncontrolled infections such as sepsis and opportunistic infections.
- Patients who are currently included in any interventional clinical trial in RA.
- RA patients in therapy with other biologics.
- Healthy donors receiving anti-inflammatory drugs
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 |
|---|---|---|
| B lymphocyte profilingAll individuals will undergo peripheral venous blood sampling and ultrasound-guided synovial tissue biopsy following a standardized procedure. B-lymphocytes will be sorted from PBMCs isolated by Ficoll gradient method using magnetic CD19-microbeads whereas tissue B-lymphocytes will be isolated from synovial tissue biopsies digested with Liberase. CD19 positive cells from PBMC will be incubated with pro-inflammatory molecules in presence or absence of Ubadacitinib. After stimulation, CD19 positive cells will be collected and processed for single cell RNA sequencing. Moreover, the impact of JAK-1 selective inhibition on B-lymphocyte cultures stimulation will be tested using ELISA method for the assessment of cytokines/chemokines production. Synovial tissue and synovial tissue B-lymphocyte subpopulations will be assessed through FACS analysis using IgD/CD27 classification. Finally, we will compare the transcriptomic profile of synovial tissue B lymphocytes from 5 subject groups. | Other | ACPA/RFpos asyntomatic individuals, Control Group, Naive Active RA, Remission RA, Resistant RA |
Primary outcome
Peripheral blood and synovial tissue B lymphocyte atlas
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2023.
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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.
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 Rheumatoid Arthritis, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 8 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 3 Mar 2023. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Elisa Gremese (00390630159659, elisa.gremese@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peripheral blood and synovial tissue B lymphocyte atlas (time frame: 24 months). 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 3 Mar 2023.