FLARE-RA: Dissecting the Cellular and Molecular Atlas of Rheumatoid Arthritis in Sustained Remission to Identify Pathways Maintaining Remission and Triggering Flares

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Other)

Overall Status

Recruiting

CT.gov ID

NCT05952440

Collaborator

University of Glasgow (Other), Fundacion Clinic per a la Recerca Biomédica (Other), Newcastle University (Other)

130

Enrollment

Locations

Anticipated Duration (Months)

32.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The FLARE-RA study will have the following research objectives:

To establish the cellular and molecular atlas of remission RA achieved with different therapeutics aimed to identify (i) cell clusters/pathways driving disease flare or maintaining remission and (ii) provide an evidence base for developing ML tools for predicting flares.
To test the performance of a ML-derived algorithm on longitudinal remission RA cohort in a biopsy-driven study.
To dissect the cellular and molecular mechanisms of remission maintenance and joint flares.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Other: Tapering and/or discontinuation of treatment based on AI-guidance Other: No tapering and/or discontinuation of treatment based on AI-guidance Other: Tapering and/or discontinuation of treatment based on standard of care Other: No tapering and/or discontinuation of treatment based on standard of care

Study Design

Study Type:

Observational

Anticipated Enrollment :

130 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

Dissecting the Cellular and Molecular Atlas of Rheumatoid Arthritis in Sustained Remission to Identify Pathways Maintaining Remission and Triggering Flares

Actual Study Start Date :

Jul 11, 2023

Anticipated Primary Completion Date :

May 10, 2026

Anticipated Study Completion Date :

May 10, 2026

Arms and Interventions

Arm	Intervention/Treatment
RA in remission who performed synovial biopsy before treatment change	Other: Tapering and/or discontinuation of treatment based on standard of care After synovial tissue biopsy, pharmacological treatment (cDMARDs or bDMARDs) are tapered first and then bDMARDs and/or cDMARDs are discontinued based on standard of care Other: No tapering and/or discontinuation of treatment based on standard of care Ongoing therapeutic are not changed (tapered or discontinued) after synovial biopsy performance based on standard of care
RA in remission eligible to synovial biopsy before treatment change	Other: Tapering and/or discontinuation of treatment based on AI-guidance After synovial tissue biopsy, pharmacological treatment (cDMARDs or bDMARDs) are tapered first and then bDMARDs and/or cDMARDs are discontinued based on AI-guidance Other: No tapering and/or discontinuation of treatment based on AI-guidance Ongoing therapeutic are not changed (tapered or discontinued) after synovial biopsy performance based on AI-guidance Other: Tapering and/or discontinuation of treatment based on standard of care After synovial tissue biopsy, pharmacological treatment (cDMARDs or bDMARDs) are tapered first and then bDMARDs and/or cDMARDs are discontinued based on standard of care Other: No tapering and/or discontinuation of treatment based on standard of care Ongoing therapeutic are not changed (tapered or discontinued) after synovial biopsy performance based on standard of care
Subjects asymptomatic for joint inflammation without ACPA/RF positivity

Arm

Intervention/Treatment

RA in remission who performed synovial biopsy before treatment change

Other: Tapering and/or discontinuation of treatment based on standard of care

After synovial tissue biopsy, pharmacological treatment (cDMARDs or bDMARDs) are tapered first and then bDMARDs and/or cDMARDs are discontinued based on standard of care

Other: No tapering and/or discontinuation of treatment based on standard of care

Ongoing therapeutic are not changed (tapered or discontinued) after synovial biopsy performance based on standard of care

RA in remission eligible to synovial biopsy before treatment change

Other: Tapering and/or discontinuation of treatment based on AI-guidance

After synovial tissue biopsy, pharmacological treatment (cDMARDs or bDMARDs) are tapered first and then bDMARDs and/or cDMARDs are discontinued based on AI-guidance

Other: No tapering and/or discontinuation of treatment based on AI-guidance

Ongoing therapeutic are not changed (tapered or discontinued) after synovial biopsy performance based on AI-guidance

Other: Tapering and/or discontinuation of treatment based on standard of care

After synovial tissue biopsy, pharmacological treatment (cDMARDs or bDMARDs) are tapered first and then bDMARDs and/or cDMARDs are discontinued based on standard of care

Other: No tapering and/or discontinuation of treatment based on standard of care

Ongoing therapeutic are not changed (tapered or discontinued) after synovial biopsy performance based on standard of care

Subjects asymptomatic for joint inflammation without ACPA/RF positivity

Outcome Measures

Primary Outcome Measures

Establishment of cellular and molecular atlas of remission RA [months 1-12]
To establish the cellular and molecular atlas of remission RA achieved with different therapeutics aimed to identify (i) cell clusters/pathways driving disease flare or maintaining remission and (ii) provide an evidence base for developing ML tools for predicting flares.

Secondary Outcome Measures

To test the performance of a ML-derived algorithm on longitudinal remission RA cohort in a biopsy-driven study. [months 13-36]
To test the performance of a ML-derived algorithm on longitudinal remission RA cohort in a biopsy-driven study.
To dissect the cellular and molecular mechanisms of remission maintenance and joint flares [months 13-36]
To dissect the cellular and molecular mechanisms of remission maintenance and joint flares in in vivo and in vitro systems

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

Rheumatoid Arthritis classified based on the 2010 EULAR/ACR Classification Criteria
Stable treatment with cDMARDs and/or bDMARDs (≥12 months)
Stable remission status (at least DAS28-CRP<2.6) (≥6 months)
No concomitant steroid treatment (≥6 months)
Absence of Power-Doppler signal at ultrasound assessment (wrist, MCP, PIP, Knee, ankle and II-V MTP bilaterally) in 3 evaluations 3 months apart.

Exclusion Criteria:

DAS28-CRP≥2.6
Presence of Power-Doppler signal ≥1 at ultrasound assessment (wrist, MCP, PIP, Knee, ankle and II-V MTP bilaterally)
Other chronic inflammatory disease

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Division of Rheumatology	Rome	Italy	00168
2	Hospital Clinic and Fundació Clinic per la Recerca Biomèdica	Barcelona	Spain
3	Research into Inflammatory Arthritis Centre Versus Arthritis (RACE)	Glasgow	United Kingdom
4	Newcastle University	Newcastle Upon Tyne	United Kingdom

Sponsors and Collaborators

Fondazione Policlinico Universitario Agostino Gemelli IRCCS
University of Glasgow
Fundacion Clinic per a la Recerca Biomédica
Newcastle University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

ClinicalTrials.gov Identifier:

NCT05952440

Other Study ID Numbers:

5600

First Posted:

Jul 19, 2023

Last Update Posted:

Jul 21, 2023

Last Verified:

May 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Study Results

No Results Posted as of Jul 21, 2023