National Cohort of Subjects at Risk of Developing Rheumatoid Arthritis

NCT06876064 | Not Yet Recruiting

• 2 other identifiers: RECHMPL24_0015Eudra CT/ID-RCB
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

PROMESS 1 is a multicenter cohort interventional study aiming at analyzing the factors associated with the risk of developing clinical arthritis among exposures or combinations of exposures in patients at risk of rheumatoid arthritis (RA), as they have high levels of anti-citrullinated peptides autoantibodies (ACPA ≥2 N). The primary endpoint is the occurrence of clinical arthritis confirmed by ultrasound at two years of following for the subject's groups at risk of RA. This may be explained by the following exposures or combinations of exposures: smoking, occupational exposure, physical activity, diet, hormonal exposure, drug exposure, trauma and psychological stress. Other factors may also explain the occurrence of clinical arthritis:

• Other symptoms
• Comorbidities, medical history, drug exposures
• Current biology: ACPA levels, rheumatoid factor levels and isotypes, CRP levels at baseline, etc.
• Ultrasound and MRI abnormalities.

Conditions

Rheumatoid Arthritis (RA)

Keywords

at-risk; ACPA; Rheumatoid arthritis; Exposome; Prediction

Outcome Measures

Primary Outcomes (1)

• Risk of developing clinical arthritis

  To analyze the factors associated with the risk of developing clinical arthritis confirmed by ultrasound among exposures or combinations of exposures in patients at high risk of RA.

  From the baseline to the end of the follow-up at 2 years

Secondary Outcomes (61)

• Quantitative difference in Food Frequency Questionnaire (FFQ) between the 4 groups of subjects included, varying from never or rarely to daily or multiple times per day.

  At baseline

• Quantitative difference in National Observatory for Physical Activity and Sedentariness -Physical Activity Questionnaire (ONAPS-PAQ) expressed in MET (Metabolic Equivalent of Task) per week between the 4 groups of subjects included.

  At baseline

• Quantitative difference in patient-reported exposure outcome Alcohol and Substance Involvement Screening Test (ASSIST) score between the 4 groups of subjects included.

  At baseline

• Quantitative difference in Fagerström Test for Nicotine Dependence (FTND) score between the 4 groups of subjects included.

  At baseline

• Compare the exposure to pollution between the 4 groups of subjects included. "Exposure to pollution will be assessed by cross-referencing residential addresses with the Chimère database.

  At baseline

Study Arms (4)

Group 1

A total of 50 subjects will be recruited: individuals with ACPA≥2 N and clinically suspect arthralgia (CSA criteria ≥4) or those with ACPA≥N and rheumatoid factor≥2N along with clinically suspect arthralgia (CSA criteria ≥4). These subjects have an estimated 50% risk of progression to RA within 2 years.

Biological: Blood test; Biological: Urine test; Other: stool collection; Other: saliva collection; Other: Induced expectoration; Other: Hair and nails sampling; Other: Schirmer test; Radiation: Ultrasound of hands and feet; Radiation: MRI Contrast; Other: Patient questions; Diagnostic Test: Dental panoramic X-ray; Other: Consultation with a psychologist in certain centers; Other: Measurement of heart rate variability.

Group 2

A total of 50 subjects will be recruited: individuals with ACPA≥2 N who do not meet the criteria for clinically suspect arthralgia (CSA criteria \<4) or those with ACPA≥N and rheumatoid factor≥2N who also do not meet the criteria for clinically suspect arthralgia (CSA criteria \<4). These subjects have an estimated 30% risk of progression to RA within 2 years.

Biological: Blood test; Biological: Urine test; Other: stool collection; Other: saliva collection; Other: Induced expectoration; Other: Hair and nails sampling; Other: Schirmer test; Radiation: Ultrasound of hands and feet; Radiation: MRI Contrast; Other: Patient questions; Diagnostic Test: Dental panoramic X-ray; Other: Consultation with a psychologist in certain centers; Other: Measurement of heart rate variability.

Group 3

A total 25 subjects will be recruited: asymptomatic subjects (CSA criteria \<4) with a family history of RA in a first-degree relative (negative controls).

Biological: Blood test; Biological: Urine test; Other: stool collection; Other: saliva collection; Other: Induced expectoration; Other: Hair and nails sampling; Other: Schirmer test; Radiation: Ultrasound of hands and feet; Radiation: MRI Contrast; Other: Patient questions; Other: Consultation with a psychologist in certain centers; Other: Measurement of heart rate variability.

Group 4

A total of 25 subjects will be recruited: individuals with RA diagnosed at polyarthritis onset (diagnosis \<6 months) who have not yet been treated, with ACPA≥2 N or ACPA≥N and rheumatoid factor≥2N (positive controls).

Biological: Blood test; Biological: Urine test; Other: stool collection; Other: saliva collection; Other: Induced expectoration; Other: Hair and nails sampling; Other: Schirmer test; Radiation: Ultrasound of hands and feet; Radiation: MRI Contrast; Other: Patient questions; Diagnostic Test: Dental panoramic X-ray; Other: Consultation with a psychologist in certain centers; Other: Measurement of heart rate variability.

Interventions

Blood test BIOLOGICAL

A total of 60 ml of blood will be collected while fasting, using the following tubes: one PAXGene Blood RNA Tube, one PAXGene Blood DNA Tube, five 5 mL serum tubes, five 5 mL EDTA tubes and one 2 mL EDTA tube for microbiota DNA analysis.

Group 1; Group 2; Group 3; Group 4

Urine test BIOLOGICAL

Urine will be collected, while fasting and after the administration of lactulose/ mannitol to assess intestinal permeability.

Group 1; Group 2; Group 3; Group 4

stool collection OTHER

Stool samples will be collected either at the hospital or at home using a dedicated kit.

Group 1; Group 2; Group 3; Group 4

saliva collection OTHER

5 ml of saliva will be collected and saliva microbiome DNA will be collected using an OMNIgene Oral kit.

Group 1; Group 2; Group 3; Group 4

Induced expectoration OTHER

inhalation of salbutamol, measurement of peak expiratory flow by screening spirometry (15 min later), inhalation of a hypertonic aerosol for 3 periods of 7 min. At the end of each inhalation period, the induced sputum is collected and the peak expiratory flow is measured to prevent possible bronchospasms

Group 1; Group 2; Group 3; Group 4

Hair and nails sampling OTHER

Hair and nails samples will be collected.

Group 1; Group 2; Group 3; Group 4

Schirmer test OTHER

To assess of tear secretion

Group 1; Group 2; Group 3; Group 4

Ultrasound of hands and feet RADIATION

To assess the risk of RA in high-risk subjects by evaluating for synovitis, tenosynovitis, or intermetatarsal-phalangeal bursitis.

Group 1; Group 2; Group 3; Group 4

MRI Contrast RADIATION

MRI of the dominant or painful hand will be performed to assess the risk of RA in high-risk subjects.

Group 1; Group 2; Group 3; Group 4

Patient questions OTHER

Self-questionnaires will assess factors such as ethnic origin, family history of RA, diet, physical activity, exposure to toxic substances, pollution, occupational exposures, psychological and clinical factors.

Group 1; Group 2; Group 3; Group 4

Dental panoramic X-ray DIAGNOSTIC_TEST

Performed as part of routine care to assess dental health

Group 1; Group 2; Group 4

Consultation with a psychologist in certain centers OTHER

The short-CTQ will be completed during this consultation, only in centers offering consultations with a psychologist.

Group 1; Group 2; Group 3; Group 4

Measurement of heart rate variability. OTHER

The patient will wear a belt throughout the visit 1. At the end of the day, the heart rate variability data measured by the belt will be recorded in the CRF (RR interval, heart rate variability SDNN, RMSSD, and LF/HF sympathovagal balance).

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The patients will be recruted during consultation or hospitalization.

You may qualify if:

• Age between 18 and 80 years old
• Group 1: Individuals with high risk of RA (ACPA ≥ 2N or ACPA ≥ N and rheumatoid factor ≥ 2N) and clinical signs of arthralgia (CSA criteria ≥ 4).
• Group 2: High-risk individuals (ACPA ≥ 2N or ACPA ≥ N and rheumatoid factor ≥ 2N) without clinical arthralgia (CSA criteria \< 4).
• Group 3: First-degree relatives of RA patients (no symptoms, negative controls).
• Group 4: Newly diagnosed untreated RA patients (ACPA ≥ 2N or ACPA ≥ N and rheumatoid factor ≥ 2N) (positive controls).

You may not qualify if:

• Groupe1-2-3:
• All groups:
• Taking current or past background treatment for RA, even for another indication
• Corticosteroid therapy ≥10 mg at baseline and in the previous week
• Presence of another connective tissue disease (Sjögren's, dermatomyositis, scleroderma, Sharp syndrome, etc.)
• Subject unable to read and/or write
• Inability to follow the patient during the study period
• Failure to obtain consent
• Non-affiliation to a social security scheme,
• Persons placed under legal protection, under curatorship or under guardianship
• Pregnant or breastfeeding women
• Person participating in another intervention research including an

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• Nantes University Hospital: collaborator
• Assistance Publique Hopitaux De Marseille: collaborator
• UNIVERSITY HOSPITAL, ORLEANS: collaborator
• Bicetre Hospital: collaborator
• Saint Antoine University Hospital: collaborator
• Groupe Hospitalier Pitie-Salpetriere: collaborator
• University Hospital, Brest: collaborator
• Assistance Publique - Hôpitaux de Paris: collaborator
• University Hospital, Bordeaux: collaborator
• Hôpital Cochin: collaborator

Study Sites (1)

CHU Montpellier

Montpellier, Hérault, 34000, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood collection: A total of 60 ml of blood will be collected while fasting, using the following tubes: one PAXGene Blood RNA Tube, one PAXGene Blood DNA Tube, five 5 mL serum tubes, five 5 mL EDTA tubes and one 2 mL EDTA tube for microbiota DNA analysis. Urine collection: Urine will be collected, while fasting and after the administration of lactulose/ mannitol to assess intestinal permeability. Stool collection: Stool samples will be collected either at the hospital or at home using a dedicated kit. Saliva collection: 5 ml of saliva will be collected and saliva microbiome DNA will be collected using an OMNIgene Oral kit. Induced expectoration: Induced sputum is collected after the inhalation of salbutamol (hypertonic aerosol). Hair sampling: Hair samples will be collected.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Hematologic Tests; Urinalysis; Wettability; Radiography, Panoramic; Referral and Consultation

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Clinical Chemistry Tests; Diagnostic Techniques, Urological; Hydrophobic and Hydrophilic Interactions; Chemical Phenomena; Surface Properties; Radiography, Dental; Radiography; Diagnostic Imaging; Diagnosis, Oral; Dentistry; Professional Practice; Organization and Administration; Health Services Administration

Central Study Contacts

CLAIRE DAIEN, PROFESSOR

CONTACT

00 33 6 85 40 27 87; c-daien@chu-montpellier.fr

Study Design

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

Study Record Dates

• First Submitted: December 24, 2024
• First Posted: March 14, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)