Integrative AI-Based Multiomic and Neurophysiological Profiling of Chronic Pain in Rheumatoid Arthritis

NCT07769619 | Recruiting

• 1 other identifier: 2023/ABM/02/00005/P/02
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease in which pain remains the most prominent and burdensome symptom from the patient's perspective. Although the introduction of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) has significantly improved the control of inflammatory activity, an estimated 20-30% of patients continues to experience persistent moderate-to-severe pain despite achieving clinical remission. This discordance between objective inflammatory markers and subjective pain perception reflects an important unmet clinical need and suggests that chronic pain in RA may become partially or fully independent of peripheral inflammation, driven instead by central sensitization and nociplastic mechanisms. The RA-PAIN-AI study is a prospective, observational, case-control study integrating clinical assessment, patient-reported outcome measures, neurophysiological evaluation, and multiomic profiling, analyzed using artificial intelligence (AI)-based methods. Two groups of adult patients with RA are enrolled: a study group of patients with active disease qualifying for biological therapy under the Polish national drug program B.33, and a control group of patients in sustained clinical remission (at least 1.5 years) under biological therapy, without clinically significant chronic pain. All participants undergo clinical assessment, standardized questionnaires, peripheral blood collection at the baseline (Visit 1) and follow-up (Visit 2) visits. Electroencephalography (EEG) is offered as an optional procedure, at the discretion of the investigator. Biological samples are analyzed using advanced multiomic technologies, including whole genome sequencing (genomics), mRNA expression profiling (transcriptomics), and measurement of circulating proteins (secretomics). All clinical, biological, and neurophysiological data are then integrated using AI methods, including dimensionality reduction, clustering, and supervised machine learning, to identify distinct pain-related patient subtypes (endotypes). The primary objective of the study is to identify and characterize clinical, neurophysiological, and multiomic signatures associated with chronic pain in RA. Expected outcomes include identification of biomarkers predictive of chronic pain persistence despite effective anti-inflammatory treatment, improved differentiation between inflammation-driven pain and pain mediated by central nervous system changes, and support for the development of more personalized, mechanism-based treatment strategies in rheumatology. The study is non-interventional: no experimental therapeutic interventions are administered, and all participants continue to receive standard clinical care. All biological analyses are performed ex vivo.

Conditions

Rheumatoid Arthritis (RA; Chronic Pain

Keywords

multiomics; pain endotypes; precision medicine; biomarkers; artificial intelligence; electroencephalography; nociplastic pain; secretomics; transcriptomics; ACPA

Outcome Measures

Primary Outcomes (3)

• Multiomic Profiles Associated With Chronic Pain in Rheumatoid Arthritis

  Genomic, transcriptomic, and secretomic profiles associated with chronic pain in rheumatoid arthritis.

  Baseline (Day 0) and Visit 2 (3-6 months after baseline)

• Integrated Differentiation Between Study Groups

  Integrated clinical, biological, and neurophysiological features differentiating participants with active rheumatoid arthritis and chronic pain from participants with rheumatoid arthritis in sustained remission without clinically significant chronic pain.

  Baseline (Day 0) and Visit 2 (3-6 months after baseline)

• AI-Based Classification of Pain-Related Endotypes

  Development of integrative artificial intelligence-based models for classification of pain-related endotypes using clinical, multiomic, and neurophysiological data.

  Baseline (Day 0) and Visit 2 (3-6 months after baseline)

Secondary Outcomes (19)

• Pain Intensity Assessed Using the Visual Analogue Scale.

  Baseline (Day 0) and Visit 2 (3-6 months after baseline)

• Functional Status Assessed Using the Health Assessment Questionnaire.

  Baseline (Day 0) and Visit 2 (3-6 months after baseline)

• Health-Related Quality of Life Assessed Using the EuroQol 5 Dimensions 5 Levels Index Value.

  Baseline (Day 0) and Visit 2 (3-6 months after baseline)

• Health-Related Quality of Life Assessed Using the Short Form Health Survey.

  Time Frame: Baseline, Day 0, and Visit 2, 3-6 months after baseline.

• Depressive Symptoms Assessed Using the Patient Health Questionnaire-9.

  Baseline (Day 0) and Visit 2 (3-6 months after baseline)

Study Arms (2)

Group 1 - Active RA With Chronic Pain (Study Group)

Group 1 - Active RA With Chronic Pain (Study Group) Description: Adult patients with confirmed rheumatoid arthritis in the active phase of disease, qualified for initiation of biological therapy under the Polish national drug program B.33 (Treatment of rheumatoid arthritis and juvenile idiopathic arthritis with aggressive course; ICD-10: M05, M06, M08). Participants undergo clinical assessment, biological sample collection (peripheral blood approximately 30 mL), standardized questionnaire evaluation, and, optionally (at the discretion of the investigator), EEG assessment. Intervention(s): No therapeutic intervention. Study procedures: blood collection, PROM assessment, optional EEG (at the discretion of the investigator), multiomic profiling (ex vivo).

Group 2 - RA in Sustained Remission Without Chronic Pain (Control Group)

Description: Adult patients with confirmed rheumatoid arthritis in sustained clinical remission for at least 1.5 years under biological therapy, with good treatment tolerance and not reporting current chronic pain in clinical interview. Participants undergo the same assessment procedures as the study group. Intervention(s): No therapeutic intervention. Same study procedures as Group 1.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with confirmed rheumatoid arthritis recruited during routine clinical care visits at a tertiary rheumatology referral center (4th Military Clinical Hospital with Polyclinic, Wrocław, Poland). The study population includes patients with active RA qualifying for biological therapy and patients in sustained clinical remission under biological therapy.

You may qualify if:

• Age ≥18 years.
• Confirmed diagnosis of rheumatoid arthritis according to applicable classification criteria.
• Active phase of the disease requiring initiation of biological therapy.
• Qualification for treatment under the national drug program B.33: "Treatment of rheumatoid arthritis and juvenile idiopathic arthritis with aggressive course (ICD-10: M05, M06, M08)".
• Ability to provide written informed consent.
• Willingness to participate in clinical assessments, EEG, biological sample collection, and questionnaire-based evaluation.

You may not qualify if:

• Contraindications to biological therapy as defined by the Polish Society of Rheumatology recommendations and the National Health Fund (NFZ) requirements under the B.33 drug program.
• Inability to provide informed consent.
• Any condition that, in the opinion of the investigator, may interfere with study participation or data interpretation.
• Age ≥18 years
• Confirmed diagnosis of rheumatoid arthritis.
• Ongoing biological therapy with sustained remission for at least 1.5 years and good tolerance of the treatment.
• No current chronic pain reported in the clinical interview.
• Ability to provide written informed consent.
• Willingness to participate in study procedures, including biological sampling, EEG and questionnaire assessments.

Sponsors & Collaborators

• Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences: collaborator
• 4th Military Clinical Hospital with Polyclinic, Poland: lead
• Lukasiewicz - PORT Polish Center for Technology Development: collaborator
• Wrocław University of Science and Technology: collaborator

Study Sites (1)

4th Military Clinical Hospital with Polyclinic (4WSzKzP SPZOZ)

Wroclaw, 50-981, Poland

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid; Chronic Pain; Nociplastic Pain

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Mariusz Kiszka, Płk lek.

  4th Military Clinical Hospital with Polyclinic (4WSzKzP SPZOZ)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wojciech Tanski, gen. bryg. dr hab. n. med.

CONTACT

0048261 660 321; cwbk@4wsk.pl

Anna Skotny, dr n. med.

CONTACT

askotny@4wsk.pl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2026
• First Posted: August 18, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 6, 2029
• Last Updated: August 18, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share

Locations

PL (1)