- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05754112
JAK-i on RA B-lymphocytes Tolerance and Disease Resolution Through JAK Signaling In Rheumatoid Arthritis
February 22, 2023 updated by: Gremese Elisa, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Observational
Enrollment (Anticipated)
50
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Elisa Gremese
- Phone Number: 00390630159659
- Email: elisa.gremese@policlinicogemelli.it
Study Locations
-
-
-
Rome, Italy, 00168
- Recruiting
- Division of Clinical Immunology, Fondazione Policlinico Universitario A. Gemelli-IRCCS
-
Contact:
- Elisa Gremese, Prof.
- Phone Number: 00390630159659
- Email: elisa.gremese@policlinicogemelli.it
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Sampling Method
Probability Sample
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.
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
ACPA/RFpos asyntomatic individuals
ACPA and/or RF positive individuals without active arthritis
|
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.
|
Naive Active RA
Treatment-naive active RA (disease duration<1 year)
|
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.
|
Resistant RA
Active despite treatment RA
|
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.
|
Remission RA
RA in sustained clinical and ultrasound remission
|
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.
|
Control Group
Individuals asymptomatic for joint inflammation without ACPA/RF positivity
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Peripheral blood and synovial tissue B lymphocyte atlas
Time Frame: 24 months
|
24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 29, 2021
Primary Completion (Anticipated)
May 2, 2023
Study Completion (Anticipated)
December 31, 2023
Study Registration Dates
First Submitted
February 22, 2023
First Submitted That Met QC Criteria
February 22, 2023
First Posted (Estimate)
March 3, 2023
Study Record Updates
Last Update Posted (Estimate)
March 3, 2023
Last Update Submitted That Met QC Criteria
February 22, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 4109
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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.
Clinical Trials on Rheumatoid Arthritis
-
Janssen Research & Development, LLCWithdrawnActive Rheumatoid Arthritis; Rheumatoid Arthritis
-
Centocor, Inc.CompletedRheumatoid Arthritis, Juvenile
-
National Institute of Arthritis and Musculoskeletal...Children's Hospital Medical Center, CincinnatiCompleted
-
University of PittsburghNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedRheumatoid Arthritis | Juvenile Rheumatoid ArthritisUnited States
-
University of Missouri-ColumbiaCompletedJuvenile Rheumatoid ArthritisUnited States
-
Richard Burt, MDTerminated
-
Universidad Autonoma de Nuevo LeonCompletedRheumatoId ArthritisMexico
-
Hamad Medical CorporationUnknownRHEUMATOID ARTHRITISQatar
-
AmgenTerminated
-
Children's Hospital Medical Center, CincinnatiNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedJuvenile Rheumatoid ArthritisUnited States
Clinical Trials on B lymphocyte profiling
-
National Cancer Institute (NCI)Completed
-
Karolinska InstitutetActive, not recruitingChronic Atrophic GastritisSweden
-
University Health Network, TorontoActive, not recruitingCarcinoma, Pancreatic DuctalCanada
-
Avera McKennan Hospital & University Health CenterWithdrawnMetastatic Breast Cancer | Breast Tumor | Advanced Gynecologic CancerUnited States
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveBelgium
-
National Cancer Institute (NCI)CompletedProstate CancerUnited States
-
University of HelsinkiHelsinki University Central HospitalRecruiting
-
Odense University HospitalRecruiting
-
Dana-Farber Cancer InstituteCharles H. Hood FoundationRecruitingMyelodysplastic Syndromes | Leukemia | Myeloproliferative SyndromeUnited States
-
University of DundeeBritish Lung Foundation; Newcastle University; University of Leicester; University... and other collaboratorsActive, not recruitingIdiopathic Pulmonary Fibrosis | Lung Diseases, Interstitial | Idiopathic Interstitial Pneumonias | Alveolitis, Extrinsic Allergic | Lung; Disease, Interstitial, With Fibrosis | Bird Fancier's LungUnited Kingdom