SAPHO SyndromeSAPHO-ScreenNCT07081880
Study of the Pathophysiological Mechanisms Involved in the SAPHO Syndrome: Genetic Component and Immune Response
An observational study of SAPHO Syndrome, run by Fondation Hôpital Saint-Joseph at 2 sites in France.
Trial summary
SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) is a chronic inflammatory rheumatism associating bone or joint lesions and dermatological manifestations dominated by severe acne and palmar and palmoplantar pustulosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SAPHO Syndrome
- What is being tested?
- biological sampling
- How many people
- 100 participants
- Where
- 2 sitesFrance
- Study dates
- 15 Jul 2025to 15 May 2035
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patient diagnosed with SAPHO syndrome
Who may be able to join
- Patient aged ≥ 18 years
- Patient diagnosed with SAPHO syndrome
- Weight > 35 kg
- Patient affiliated with a health insurance plan
- French-speaking patient
- Patient who has given free, informed, and written consent
Who cannot join
- Patient under guardianship or curatorship
- Patient deprived of liberty
- Patient under legal protection
- Pregnant or breastfeeding patient
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France2 sites, 2 recruiting
- Recruiting
Hôpital Cochin
Paris
Olivier FOGEL, MD, +331 58 41 13 70, olivier.fogel@aphp.fr
- Recruiting
Hôpital Paris Saint Joseph
Paris
Gilles HAYEM, MD, +33144128100, ghayem@ghpsj.fr
About this study
SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) is a chronic inflammatory rheumatism associating bone or joint lesions and dermatological manifestations dominated by severe acne and palmar and palmoplantar pustulosis. Prevalence of SAPHO syndrome is estimated at 1/50000 in France, but this figure is probably underestimated due to frequent misdiagnosis. Osteoarticular manifestations form a rheumatic picture very similar to that of other forms of spondyloarthritis (SpA). The latest French recommendations do not distinguish SAPHO syndrome from other forms of SpA. As a result, the management of SAPHO remains fairly heterogeneous, essentially based on the local experience of rheumatologists. Delays in diagnosis and difficulties in finding effective treatment can result in significant disability and reduced quality of life, particularly detrimental in a young population (age at diagnosis is usually between 30 and 40). The wide spectrum of clinical presentations of SAPHO syndrome explains the complexity of managing this condition. Understanding the pathophysiological mechanisms underlying these different forms of the disease is a major challenge for personalized medicine. SAPHO syndrome is a multifactorial disease that is a result of interaction of genetic, environmental, immunological and infectious factors. In the classification of immune-mediated inflammatory diseases, SAPHO syndrome lies midway between autoinflammatory diseases involving the innate immune response and spondyloarthritis associated with abnormalities in the adaptive immune response. Indeed, while the clinical phenotype may resemble spondyloarthritis in certain aspects, the identification of genetic forms of chronic relapsing osteitis, such as DIRA syndrome or Majeed syndrome, argues in favor of an autoinflammatory origin of SAPHO syndrome. Although osteitis is reputed to be sterile, an infectious initiating factor has long been suspected in this disease. Among the bacterial agents, antigens antigens from Cutibacterium acnes were detected in bone biopsies from patients with SAPHO syndrome. It has been suggested that this bacterium may play a role in triggering a systemic inflammatory response systemic inflammatory response mediated in particular by IL-1β.
Read the detailed description
Although neutrophils (PNN) are the most abundant leukocytes in the circulation and form a first line of innate immune defense, they are difficult to study because they have a short lifespan and, after migrating into tissues, are rapidly eliminated by macrophages. PNN play a central role in the early phase of SpA development, and contribute to the various tissue damage observed. PNN are recruited from the circulation and enter target tissues such as joints, enthesis, digestive tract, skin and eyes, where they produce neutrophil extracellular traps (NETs), cytokines and chemokines that attract other immune cells. In SAPHO syndrome, bone biopsy usually reveals an infiltrate of PNNs, at least in the early stages of the disease. To date, no study has performed extensive phenotyping of circulating blood to identify over- or under-represented cell populations, which could thus be implicated in the disease.
Studies showed an increase in the Th17 population in SAPHO patients, elevated low density granulocytes and neutrophil extracellular traps formation, as well as specific protein patterns associated with inflammation. Genetic studies, particularly in Chinese populations, have revealed potential associations with IL-23R and IL-4 genes, as well as SNPs in PEX16 and IQCA1L. However, no large-scale genetic analysis has been conducted in European/Caucasian populations. While certain forms of SAPHO syndrome suggest a genetic predisposition, studies targeting genes associated with monogenic disorders like Majeed, PAPA, and DIRA have yielded negative results. Chinese studies have indicated involvement of genes like CSF2RA, NOD2, MEGF6, and ADAM5. Despite genetic predisposition suspicions, robust associations have not been identified, particularly in Caucasian populations, warranting further research.
- Conditions
- SAPHO Syndrome
- Being tested
- biological sampling
- Medical subject headings
- Acquired Hyperostosis Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
biological samplingOther
DNA and Cells will be sampled
| Study group | Role | What they receive |
|---|---|---|
| biological sampling | Not described Receives: Other: biological sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Investigating a Genetic Predisposition to SAPHO Syndrome
Comparison of allelic frequencies in patients with SAPHO syndrome versus the general population
Measured: at baseline
Secondary outcomes (7)
Estimating the Degree of Genetic Component Overlap Between SAPHO Syndrome and Axial SpA
Comparison of allelic frequencies in patients with SAPHO syndrome versus patients with severe and non-severe axial SpA
Measured: at baseline
Studying the Genetic Component Based on Different Phenotypes of SAPHO Syndrome
comparison of allelic frequencies among patients:
With pure osteitis form of SAPHO syndrome vs. those with axial form of the disease With cutaneous involvement vs. without cutaneous involvement
Measured: at baseline
Studying the Functional Consequences of Variants Associated with SAPHO Syndrom, on the protein level
comparison of Expression level of protein of the different variants in sorted cells and plasma
Measured: at baseline, at 6 months, and every year for 9 years
Studying the Functional Consequences of Variants Associated with SAPHO Syndrom, on the transciptom level
comparison of Expression level of mRNA of the different variants in sorted cells and plasma
Measured: at baseline, at 6 months, and every year for 9 years
Phenotypic Characterization of Different Circulating Immune Subpopulations in Patients with SAPHO Syndrome
percentage of the different circulating immune cell subtypes (monocytes, T lymphocytes and subclasses, B lymphocytes, PNN, and NK) and rare populations (MAIT, γδ lymphocytes, etc.) determined by flow cytometry techniques
Measured: at baseline and at 6months
Measurement of Cytokines of Interest
Dosage of cytokine done by ELISA in the plasma of SAPHO patients and control populations.
Measured: at baseline and at 6months
Identification of Prognostic Factors for Severity of SAPHO Syndrome and/or Response to Different Treatments
clinical evalution of the severity of the disease and its response to the treatment
Measured: at baseline and at 6months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2025
- Study start15 Jul 2025
- Primary completion15 Jul 2028 (estimated)
- Study completion15 May 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SAPHO SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondation Hôpital Saint-Joseph
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07081880
- Sponsor's protocol ID
- 644_SAPHO-Screen
- Acronym
- SAPHO-Screen
- Status last verified
- Dec 2025
- First submitted
- 18 Jun 2025
- Last updated
- 24 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Pathophysiological Mechanisms Involved in the SAPHO Syndrome: Genetic Component and Immune Response
- ClinicalTrials.gov ID
- NCT07081880
- Acronym / sponsor ID
- SAPHO-Screen / 644_SAPHO-Screen
- Conditions
- SAPHO Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Fondation Hôpital Saint-JosephUniversity, hospital or other
- Study start
- 15 Jul 2025 (actual)
- Primary completion
- 15 Jul 2028 (estimated)
- Study completion
- 15 May 2035 (estimated)
- First posted
- 23 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) is a chronic inflammatory rheumatism associating bone or joint lesions and dermatological manifestations dominated by severe acne and palmar and palmoplantar pustulosis. Prevalence of SAPHO syndrome is estimated at 1/50000 in France, but this figure is probably underestimated due to frequent misdiagnosis. Osteoarticular manifestations form a rheumatic picture very similar to that of other forms of spondyloarthritis (SpA). The latest French recommendations do not distinguish SAPHO syndrome from other forms of SpA. As a result, the management of SAPHO remains fairly heterogeneous, essentially based on the local experience of rheumatologists. Delays in diagnosis and difficulties in finding effective treatment can result in significant disability and reduced quality of life, particularly detrimental in a young population (age at diagnosis is usually between 30 and 40). The wide spectrum of clinical presentations of SAPHO syndrome explains the complexity of managing this condition. Understanding the pathophysiological mechanisms underlying these different forms of the disease is a major challenge for personalized medicine. SAPHO syndrome is a multifactorial disease that is a result of interaction of genetic, environmental, immunological and infectious factors. In the classification of immune-mediated inflammatory diseases, SAPHO syndrome lies midway between autoinflammatory diseases involving the innate immune response and spondyloarthritis associated with abnormalities in the adaptive immune response. Indeed, while the clinical phenotype may resemble spondyloarthritis in certain aspects, the identification of genetic forms of chronic relapsing osteitis, such as DIRA syndrome or Majeed syndrome, argues in favor of an autoinflammatory origin of SAPHO syndrome. Although osteitis is reputed to be sterile, an infectious initiating factor has long been suspected in this disease. Among the bacterial agents, antigens antigens from Cutibacterium acnes were detected in bone biopsies from patients with SAPHO syndrome. It has been suggested that this bacterium may play a role in triggering a systemic inflammatory response systemic inflammatory response mediated in particular by IL-1β.
Detailed description
Although neutrophils (PNN) are the most abundant leukocytes in the circulation and form a first line of innate immune defense, they are difficult to study because they have a short lifespan and, after migrating into tissues, are rapidly eliminated by macrophages. PNN play a central role in the early phase of SpA development, and contribute to the various tissue damage observed. PNN are recruited from the circulation and enter target tissues such as joints, enthesis, digestive tract, skin and eyes, where they produce neutrophil extracellular traps (NETs), cytokines and chemokines that attract other immune cells. In SAPHO syndrome, bone biopsy usually reveals an infiltrate of PNNs, at least in the early stages of the disease. To date, no study has performed extensive phenotyping of circulating blood to identify over- or under-represented cell populations, which could thus be implicated in the disease.
Studies showed an increase in the Th17 population in SAPHO patients, elevated low density granulocytes and neutrophil extracellular traps formation, as well as specific protein patterns associated with inflammation. Genetic studies, particularly in Chinese populations, have revealed potential associations with IL-23R and IL-4 genes, as well as SNPs in PEX16 and IQCA1L. However, no large-scale genetic analysis has been conducted in European/Caucasian populations. While certain forms of SAPHO syndrome suggest a genetic predisposition, studies targeting genes associated with monogenic disorders like Majeed, PAPA, and DIRA have yielded negative results. Chinese studies have indicated involvement of genes like CSF2RA, NOD2, MEGF6, and ADAM5. Despite genetic predisposition suspicions, robust associations have not been identified, particularly in Caucasian populations, warranting further research.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| biological sampling | – | Other: biological sampling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patient diagnosed with SAPHO syndrome
Key inclusion criteria (6 listed)
- Patient aged ≥ 18 years
- Patient diagnosed with SAPHO syndrome
- Weight > 35 kg
- Patient affiliated with a health insurance plan
- French-speaking patient
Key exclusion criteria (4 listed)
- Patient under guardianship or curatorship
- Patient deprived of liberty
- Patient under legal protection
- Pregnant or breastfeeding patient
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| biological samplingDNA and Cells will be sampled | Other | biological sampling |
Primary outcome
Investigating a Genetic Predisposition to SAPHO Syndrome
Time frame: at baseline
Comparison of allelic frequencies in patients with SAPHO syndrome versus the general population
7 secondary outcomes
Estimating the Degree of Genetic Component Overlap Between SAPHO Syndrome and Axial SpA
Time frame: at baseline
Studying the Genetic Component Based on Different Phenotypes of SAPHO Syndrome
Time frame: at baseline
Studying the Functional Consequences of Variants Associated with SAPHO Syndrom, on the protein level
Time frame: at baseline, at 6 months, and every year for 9 years
Studying the Functional Consequences of Variants Associated with SAPHO Syndrom, on the transciptom level
Time frame: at baseline, at 6 months, and every year for 9 years
Phenotypic Characterization of Different Circulating Immune Subpopulations in Patients with SAPHO Syndrome
Time frame: at baseline and at 6months
Measurement of Cytokines of Interest
Time frame: at baseline and at 6months
Identification of Prognostic Factors for Severity of SAPHO Syndrome and/or Response to Different Treatments
Time frame: at baseline and at 6months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2025.
- Individual participant dataSharing planned: No
Related trials for SAPHO Syndrome
RecruitingPhase 2/3
Study of the Efficacy and Safety of Etanercept Treatment in Patients With SAPHO Syndrome
SAPHO Syndrome
RecruitingObservational study
Typological Study of Sleep Pathologies During Psoriatic Rheumatism and SAPHO Syndrome: Prospective Study Within the Paris Saint-Joseph Hospital Group"
Psoriasis Arthritis, SAPHO Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of SAPHO Syndrome, run by Fondation Hôpital Saint-Joseph at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Olivier Fogel, MD (+331 58 41 13 70, olivier.fogel@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Investigating a Genetic Predisposition to SAPHO Syndrome (time frame: at baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2025.