National Cohort of Subjects at Risk of Developing Rheumatoid Arthritis

NCT ID: NCT06876064

Last Updated: 2025-10-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-10-31

Study Completion Date

2027-12-31

Brief Summary

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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

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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

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Rheumatoid Arthritis (RA)

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Blood test

Intervention Type 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.

Urine test

Intervention Type BIOLOGICAL

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

stool collection

Intervention Type OTHER

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

saliva collection

Intervention Type OTHER

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

Induced expectoration

Intervention Type 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

Hair and nails sampling

Intervention Type OTHER

Hair and nails samples will be collected.

Schirmer test

Intervention Type OTHER

To assess of tear secretion

Ultrasound of hands and feet

Intervention Type RADIATION

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

MRI Contrast

Intervention Type RADIATION

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

Patient questions

Intervention Type 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.

Dental panoramic X-ray

Intervention Type DIAGNOSTIC_TEST

Performed as part of routine care to assess dental health

Consultation with a psychologist in certain centers

Intervention Type OTHER

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

Measurement of heart rate variability.

Intervention Type 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 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.

Blood test

Intervention Type 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.

Urine test

Intervention Type BIOLOGICAL

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

stool collection

Intervention Type OTHER

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

saliva collection

Intervention Type OTHER

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

Induced expectoration

Intervention Type 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

Hair and nails sampling

Intervention Type OTHER

Hair and nails samples will be collected.

Schirmer test

Intervention Type OTHER

To assess of tear secretion

Ultrasound of hands and feet

Intervention Type RADIATION

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

MRI Contrast

Intervention Type RADIATION

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

Patient questions

Intervention Type 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.

Dental panoramic X-ray

Intervention Type DIAGNOSTIC_TEST

Performed as part of routine care to assess dental health

Consultation with a psychologist in certain centers

Intervention Type OTHER

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

Measurement of heart rate variability.

Intervention Type 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 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).

Blood test

Intervention Type 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.

Urine test

Intervention Type BIOLOGICAL

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

stool collection

Intervention Type OTHER

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

saliva collection

Intervention Type OTHER

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

Induced expectoration

Intervention Type 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

Hair and nails sampling

Intervention Type OTHER

Hair and nails samples will be collected.

Schirmer test

Intervention Type OTHER

To assess of tear secretion

Ultrasound of hands and feet

Intervention Type RADIATION

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

MRI Contrast

Intervention Type RADIATION

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

Patient questions

Intervention Type 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.

Consultation with a psychologist in certain centers

Intervention Type OTHER

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

Measurement of heart rate variability.

Intervention Type 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 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).

Blood test

Intervention Type 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.

Urine test

Intervention Type BIOLOGICAL

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

stool collection

Intervention Type OTHER

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

saliva collection

Intervention Type OTHER

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

Induced expectoration

Intervention Type 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

Hair and nails sampling

Intervention Type OTHER

Hair and nails samples will be collected.

Schirmer test

Intervention Type OTHER

To assess of tear secretion

Ultrasound of hands and feet

Intervention Type RADIATION

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

MRI Contrast

Intervention Type RADIATION

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

Patient questions

Intervention Type 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.

Dental panoramic X-ray

Intervention Type DIAGNOSTIC_TEST

Performed as part of routine care to assess dental health

Consultation with a psychologist in certain centers

Intervention Type OTHER

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

Measurement of heart rate variability.

Intervention Type 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).

Interventions

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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.

Intervention Type BIOLOGICAL

Urine test

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

Intervention Type BIOLOGICAL

stool collection

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

Intervention Type OTHER

saliva collection

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

Intervention Type 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

Intervention Type OTHER

Hair and nails sampling

Hair and nails samples will be collected.

Intervention Type OTHER

Schirmer test

To assess of tear secretion

Intervention Type OTHER

Ultrasound of hands and feet

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

Intervention Type RADIATION

MRI Contrast

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

Intervention Type RADIATION

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.

Intervention Type OTHER

Dental panoramic X-ray

Performed as part of routine care to assess dental health

Intervention Type DIAGNOSTIC_TEST

Consultation with a psychologist in certain centers

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

Intervention Type 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).

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Nantes University Hospital

OTHER

Sponsor Role collaborator

Assistance Publique Hopitaux De Marseille

OTHER

Sponsor Role collaborator

UNIVERSITY HOSPITAL, ORLEANS

UNKNOWN

Sponsor Role collaborator

Bicetre Hospital

OTHER

Sponsor Role collaborator

Saint Antoine University Hospital

OTHER

Sponsor Role collaborator

Groupe Hospitalier Pitie-Salpetriere

OTHER

Sponsor Role collaborator

University Hospital, Brest

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role collaborator

University Hospital, Bordeaux

OTHER

Sponsor Role collaborator

Hôpital Cochin

OTHER

Sponsor Role collaborator

University Hospital, Montpellier

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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CHU Montpellier

Montpellier, Hérault, France

Site Status

Countries

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France

Central Contacts

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CLAIRE DAIEN, PROFESSOR

Role: CONTACT

00 33 6 85 40 27 87

Facility Contacts

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CLAIRE DAIEN, Professor

Role: primary

+33 6 85 40 27 87

Other Identifiers

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Eudra CT/ID-RCB

Identifier Type: OTHER

Identifier Source: secondary_id

RECHMPL24_0015

Identifier Type: -

Identifier Source: org_study_id

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