Clinical trial NCT06876064: National Cohort of Subjects at Risk of Developing Rheumatoid Arthritis
Official title: National Cohort of Subjects at Risk of Developing Rheumatoid Arthritis
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Rheumatoid Arthritis (RA)
Keywords: at-risk
ACPA
Rheumatoid arthritis
Exposome
Prediction
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Nantes University Hospital
name: Assistance Publique Hopitaux De Marseille
name: UNIVERSITY HOSPITAL, ORLEANS
name: Bicetre Hospital
name: Saint Antoine University Hospital
name: Groupe Hospitalier Pitie-Salpetriere
name: University Hospital, Brest
name: Assistance Publique - Hôpitaux de Paris
name: University Hospital, Bordeaux
name: Hôpital Cochin
First posted: 2025-03-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The patients will be recruted during consultation or hospitalization.

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.

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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* Groupe1-2-3:

  • Presence of clinical joint swelling (synovitis) at the time of inclusion and previously noted by a doctor
* 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
  * exclusion period still in progress

Primary outcomes:
measure: Risk of developing clinical arthritis
timeFrame: From the baseline to the end of the follow-up at 2 years
Secondary outcomes:
measure: 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.
timeFrame: At baseline
measure: 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.
timeFrame: At baseline
measure: Quantitative difference in patient-reported exposure outcome Alcohol and Substance Involvement Screening Test (ASSIST) score between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in Fagerström Test for Nicotine Dependence (FTND) score between the 4 groups of subjects included.
timeFrame: At baseline
measure: 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.
timeFrame: At baseline
measure: Qualitative difference in a self-report integrated questionnaire for diagnosis of all functional gastrointestinal disorders in adults between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in patient-reported Francis score for Irritable Bowel Syndrome (IBS) between the 4 groups of subjects included.
timeFrame: At baseline
measure: Qualitative difference in patient-reported clinical outcome of Sleep Apnea (Berlin questionnaire) between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in Visual Analog Scale (VAS) score for patient's pain between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in Visual Analog Scale (VAS) score for patient's fatigue between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in Visual Analog Scale (VAS) score for patient's disease activity between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in Visual Analog Scale (VAS) score for disease activity on the opinion of the physician between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in Pichot Fatigue Scale score between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in State-Trait Anxiety Inventory (STAI) score between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in patient-reported outcome Posttraumatic Stress Disorder Checklist (PCL-5) score between the 4 groups of subjects included,
timeFrame: At baseline
measure: Quantitative difference in patient-reported outcome heath survey Short Form-12 (SF-12) version 2 with Physical Component Summary (PCS) and Mental Component Summary (MCS) scores between the 4 groups of subjects included
timeFrame: At baseline
measure: Quantitative difference in Insomnia Severity Index (ISI) score between the 4 groups of subjects included
timeFrame: At baseline
measure: Quantitative difference in Pain Catastrophizing Scale (PCS) score between the 4 groups of subjects included
timeFrame: At baseline
measure: Quantitative difference in Rheumatoid factor (FR) auto-antibody level between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference Anti-Citrullinated Peptide Antibodies (ACPA) level between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in C-reactive protein (CRP) level between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in Neutrophils values between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in lymphocytes values between the 4 groups of subjects included.
timeFrame: At baseline
measure: Quantitative difference in Platelets (PLT) between the 4 groups of subjects included.
timeFrame: At baseline
measure: Clinical arthritis and Clinically Suspected Arthralgias (CSA).
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in Visual Analog Scale (VAS) score for patient's pain between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in Visual Analog Scale (VAS) score for patient's fatigue between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in Visual Analog Scale (VAS) score for patient's disease activity between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in Visual Analog Scale (VAS) score for disease activity on the opinion of the physician between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in Pichot Fatigue Scale score between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in State-Trait Anxiety Inventory (STAI) score between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in patient-reported outcome Posttraumatic Stress Disorder Checklist (PCL-5) score between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in patient-reported outcome heath survey Short Form-12 (SF-12) version 2 with Physical Component Summary (PCS) and Mental Component Summary (MCS) scores between the patients who developed clinical arthritis during the 2-year f
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in Insomnia Severity Index (ISI) score between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in Pain Catastrophizing Scale (PCS) score between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in tender joints count between the patients who developed clinical arthritis during the 2-year follow-up and those who did not, among 44 joints across the body.
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Quantitative difference in tenosynovitis count between the patients who developed clinical arthritis during the 2-year follow-up and those who did not, among 16 flexor and extensor finger's tendons.
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Quantitative difference in difficulties of making a fist between the patients who developed clinical arthritis during the 2-year follow-up and those who did not. Relate this outcome to the risk of developing clinical arthritis.
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Quantitative difference in tenosynovitis between the patients who developed clinical arthritis during the 2-year follow-up and those who did not detected by ultrasound. Relate this outcome to the risk of developing clinical arthritis
timeFrame: Baseline, week 26; week 52 and week 104 visit
measure: Quantitative difference in Rheumatoid factor (FR) auto-antibody level between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Quantitative difference in Anti-Citrullinated Peptide Antibodies (ACPA) level between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Quantitative difference in C-reactive protein (CRP) level between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Quantitative difference in Neutrophils values between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Quantitative difference in lymphocytes values between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Quantitative difference in Platelets (PLT) between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Proportion of patients with ultrasound synovitis in the 2 groups at high-risk of rheumatoid factor (RA) (group 1 and 2).
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Proportion of patients with ultrasound tenosynovitis in the 2 groups at high-risk of rheumatoid factor (RA) (group 1 and 2).
timeFrame: Baseline, week 26, week 52 and week 104 visit
measure: Proportion of patients with ultrasound synovitis in the 4 groups of subjects included.
timeFrame: Baseline
measure: Proportion of patients with ultrasound tenosynovitis in the 4 groups of subjects included.
timeFrame: Baseline
measure: Quantitative difference in synovitis between the 4 groups of subjects included.
timeFrame: Baseline
measure: Quantitative difference in bone oedemes between the 4 groups of subjects included.
timeFrame: Baseline
measure: Quantitative difference in pinch between the 4 groups of subjects included.
timeFrame: Baseline
measure: Quantitative difference in erosion between the 4 groups of subjects included.
timeFrame: Baseline
measure: Quantitative difference in tenosynovitis between the 4 groups of subjects included, between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline
measure: Quantitative difference in synovitis between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline
measure: Quantitative difference in bone oedemes between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline
measure: Quantitative difference in pinch between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline
measure: Quantitative difference in erosion between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline
measure: Quantitative difference in tenosynovitis between the patients who developed clinical arthritis during the 2-year follow-up and those who did not.
timeFrame: Baseline
Other outcomes:
Locations:
city: Montpellier
country: France
facility: CHU Montpellier
state: Hérault
Study officials:
References: