NCT06876064

National Cohort of Subjects at Risk of Developing Rheumatoid Arthritis

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 150 (estimated)
• Sponsor: University Hospital, Montpellier · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Accepted

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.

Detailed description

This is a multicenter interventional cohort study. The goal of this cohort is to analyze the factors associated with the risk of developing clinical arthritis, considering individual or combined exposures, in patients at high risk of rheumatoid arthritis (RA). Four groups of adults will be included: * Group 1: 50 subjects at very high risk of RA: ACPA≥2 N or (ACPA\>N and rheumatoid factor≥2 N) + presence of clinically suspicious arthralgia (CSA criteria ≥4) * Group 2: 50 subjects at high risk of RA: ACPA≥2 N or (ACPA\>N and rheumatoid factor≥2 N) without clinically suspicious arthralgia (CSA criteria \<4) * Group 3: 25 asymptomatic subjects, 1st degree relatives of subjects with RA (negative controls) * Group 4: 25 patients with early RA prior to any disease-modifying therapy (positive controls) Patients in the control groups will be included based on the same age and sex as patients in the risk groups (1 \& 2) in the recruiting center. The primary endpoint is the occurrence of clinical arthritis, confirmed by ultrasound, after two years of follow-up in the at-risk RA groups (Groups 1 \& 2). This may be explained by the following exposures or their combinations: smoking, occupational exposure, physical activity, diet, hormonal exposure, drug exposure, trauma and psychological stress... Other factors that may contribute to the occurrence of clinical arthritis include: * Clinical elements and questionnaires assessing the other symptoms of the individuals (PRO) (subjective clinical suspicion of arthralgia CSA, painful joints at inclusion, BMI, stool consistency, functional respiratory signs, etc.) * Comorbidities and antecedents via CNAM pathology mapping and drug exposure via data on dispensing in towns from the SNDS * Current biology: ACPA levels, rheumatoid factor levels and isotypes, CRP levels at baseline, etc. * Ultrasound and MRI abnormalities. The controls groups (groups 3\&4) will allow for a cross-sectional analysis, comparing at-risk RA subjects with healthy individuals who share the same genetic background. They will have a single visit at baseline without follow-up. However, the at-risk RA groups (groups 1 \& 2) will have four visits (M0, M6, M12 et M24). In addition to routine care examinations performed in RA risk situations, subjects will undergo blood and stool sample collection at baseline and at one year. All subjects regardless of group, will undergo the following baseline assessments: MRI of the dominant hand or painful hand, a lactulose absorption test (to assess intestinal permeability), hair and saliva collection, a Schirmer test, and, in some centers, an induced sputum test (to assess pulmonary mucosa). Ultrasound of the hands and feet, as well as specific questionnaires assessing the exposome, will be conducted at all visits.

Conditions

• Rheumatoid Arthritis (RA)

Interventions

Type	Name	Description
BIOLOGICAL	Blood test	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.
BIOLOGICAL	Urine test	Urine will be collected, while fasting and after the administration of lactulose/ mannitol to assess intestinal permeability.
OTHER	stool collection	Stool samples will be collected either at the hospital or at home using a dedicated kit.
OTHER	saliva collection	5 ml of saliva will be collected and saliva microbiome DNA will be collected using an OMNIgene Oral kit.
OTHER	Induced expectoration	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
OTHER	Hair and nails sampling	Hair and nails samples will be collected.
OTHER	Schirmer test	To assess of tear secretion
RADIATION	Ultrasound of hands and feet	To assess the risk of RA in high-risk subjects by evaluating for synovitis, tenosynovitis, or intermetatarsal-phalangeal bursitis.
RADIATION	MRI Contrast	MRI of the dominant or painful hand will be performed to assess the risk of RA in high-risk subjects.
OTHER	Patient questions	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.
DIAGNOSTIC_TEST	Dental panoramic X-ray	Performed as part of routine care to assess dental health
OTHER	Consultation with a psychologist in certain centers	The short-CTQ will be completed during this consultation, only in centers offering consultations with a psychologist.
OTHER	Measurement of heart rate variability.	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).

Timeline

• Start date: 2025-10-01
• Primary completion: 2027-12-01
• Completion: 2027-12-01
• First posted: 2025-03-14
• Last updated: 2025-10-01

Locations

1 site across 1 country: France