Spondylitis, AnkylosingMETYLASNCT03092583
Analysis of DNA Methylation in Spondyloarthritis
A study testing Blood sample in people with Spondylitis, Ankylosing and Axial Spondyloarthritis, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
Trial summary
The aim of this project is to quantify global DNA methylation in patients with Ankylosing Spondylitis or Axial Spondyloarthritis as compared with control subjects. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Spondylitis, Ankylosing, Axial Spondyloarthritis, DNA Methylation
- What is being tested?
- Blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 184 participants
- Where
- 1 siteFrance
- Study dates
- 15 Feb 2017to 7 Oct 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects included in the Patient group must meet the modified New York criteria for AS, or the ASAS criteria for Ax-SpA, and must be naïve of biologic therapy (anti-TNF-α agents) at the time of inclusion, or have received but subsequently discontinued anti-TNF-α therapy at least 3 months before inclusion.
- Subjects included in the Control group must be free from any inflammatory or auto-immune disease. Subjects being followed for spinal disc disease (herniated disc) or abarticular mechanical disease (tendonitis) will be eligible, as well as healthy subjects.
- The following inclusion criteria are common to both control and patient groups:
- Adult patients (≥18 years).
- Provide written informed consent indicating that the subject has understood the aims of the study, as well as the procedures involved, and that he/she accepts to participate and adhere to the demands and restrictions imposed by the study participation.
- All subjects must have social security coverage.
- Maximum age is 80 years.
Who cannot join
- Subjects being treated by systemic corticosteroids with a prednisone equivalent dose >10 mg/day.
- Subjects with limited legal capacity.
- Subjects judged by the investigator to be unlikely to comply with study procedures
- Subjects with no social security coverage.
- Pregnant women.
- Subjects still in the exclusion period of another study, or according to the national registry of clinical trial participants.
- Inability to understand the study objectives; psychiatric disorders deemed by the investigator to be incompatible with inclusion in the study.
Trial locations and contacts
1 site in 1 country.
About this study
The aim of this project is to quantify global DNA methylation in patients with Ankylosing Spondylitis or Axial Spondyloarthritis as compared with control subjects.
Read the detailed description
Spondyloarthritis covers a group of diseases with common clinical, genetic and radiographic characteristics. Ankylosing spondylitis (AS) is the most common of these, and is usually diagnosed in the presence of bilateral sacroiliitis by conventional x-ray, according to the modified New York criteria. Axial spondyloarthritis (Ax-SpA) mainly affects the axial skeleton and progresses towards the formation of bone or bony structures around the sacro-iliac joint and spine, leading to the gradual formation of a bony bridge from the sacro-iliac joint and ligamentous ossifications to the spine. Early forms of the disease do not present such modifications to the sacro-iliac joint and therefore, show no visible sacroiliitis on conventional x-ray. Thus, it is possible to classify a patient aged <45 years with inflammatory lower back pain as having Ax-SpA, irrespective of the presence of sacroiliitis by x-ray. Indeed, inflammation of the sacro-iliac joint and spine occurs before the process of ossification and inflammation, and can be detected by MRI. This led the Assessment of SpondyloArthritis international Society (ASAS) group to propose candidate classification criteria for Ax-SpA, notably adapted to early forms of the disease. Accordingly, patients with Ax-SpA without radiographic sacroiliitis are considered to have non-radiographic Ax-SpA. Classification criteria for peripheral SpA are also available.
The determinants of AS and SpA are complex, and involve both genetic and environmental factors. In addition to these factors, several studies in recent years have also highlighted the emerging role of epigenetics in the pathophysiology of inflammatory diseases.
The term epigenetics refers to heritable and reversible modifications in gene expression without any change in the coding DNA sequence. This process may be involved in the pathophysiology of different diseases and their clinical expression. Several different epigenetic mechanisms may concur to modify gene functioning. Changes to the chromatin and to DNA (without modification of the encoding sequence itself) have been shown to be important for the control of gene expression through suppressive or permissive factors. Thus, DNA methylation could play a role in auto-immune or inflammatory diseases by regulating gene expression, particularly those coding for pro-inflammatory mediators such as certain cytokines, thereby contributing to dysregulation of the immune system.
DNA methylation is regulated by the activity of DNA methyltransferase enzymes (DNMT). In multicellular eukaryotic organisms, DNA methylation is associated with chromatin repression, and thereby, inhibition of gene expression. DNA methylation can be evaluated across the whole genome, but also at the level of a specific candidate gene, such as the gene encoding a pro-inflammatory cytokine.
The level of DNA methylation has been evaluated in rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE), and a "methylated-DNA" signature has been observed in these auto-immune diseases. Currently, there is no available data regarding DNA methylation in AS or SpA in general. In this study, the investigators aim to analyse the global DNA methylation in patients with AS or Ax-SpA.
- Being tested
- Blood sample
- Medical subject headings
- Spondylitis, Ankylosing, Axial Spondyloarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampleOther
35 mL, 7 tubes
| Study group | Role | What they receive |
|---|---|---|
| Patient group | Experimental | Subjects must meet the modified New York criteria for AS, or the ASAS criteria for Ax-SpA, and must be naïve of biologic therapy (anti-TNF-α agents) at the time of inclusion, or have received but subsequently discontinued anti-TNF-α therapy at least 3 months before inclusion. A blood sample will be drawn (35 mL) to these patients. Receives: Other: Blood sample |
| Control group | Other | Subjects must be free from any inflammatory or auto-immune disease. A blood sample will be drawn (35 mL) to these controls subjects. Receives: Other: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall level of DNA methylation
The level of methylation will be evaluated using the global quantification technique for DNA
Measured: D0 (day of inclusion)
Secondary outcomes (3)
Expression of DNMT1 and MBD2
Expression of DNMT1 and MBD2 will be quantified on RNA extracted from monocytes and CD4 T cells, by quantitative real-time polymerase chain reaction
Measured: D0 (day of inclusion)
Methylation of the promoter region of TNF
Methylation of the promoter region of TNF will be evaluated on DNA from monocytes and CD4 T cells (bisulfite genomic sequencing)
Measured: D0 (day of inclusion)
Serum TNF-α
Serum TNF-α will be quantified by ELISA.
Measured: D0 (day of inclusion)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2017
- Study start15 Feb 2017
- Primary completion7 Oct 2020
- Study completion7 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spondylitis, AnkylosingStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03092583
- Sponsor's protocol ID
- P/2015/252
- Acronym
- METYLAS
- Status last verified
- Jan 2021
- First submitted
- 17 Mar 2017
- Last updated
- 1 Feb 2021
- 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 1 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of DNA Methylation in Spondyloarthritis
- ClinicalTrials.gov ID
- NCT03092583
- Acronym / sponsor ID
- METYLAS / P/2015/252
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 184 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Study start
- 15 Feb 2017 (actual)
- Primary completion
- 7 Oct 2020 (actual)
- Study completion
- 7 Oct 2020 (actual)
- First posted
- 28 Mar 2017 (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.
The aim of this project is to quantify global DNA methylation in patients with Ankylosing Spondylitis or Axial Spondyloarthritis as compared with control subjects.
Detailed description
Spondyloarthritis covers a group of diseases with common clinical, genetic and radiographic characteristics. Ankylosing spondylitis (AS) is the most common of these, and is usually diagnosed in the presence of bilateral sacroiliitis by conventional x-ray, according to the modified New York criteria. Axial spondyloarthritis (Ax-SpA) mainly affects the axial skeleton and progresses towards the formation of bone or bony structures around the sacro-iliac joint and spine, leading to the gradual formation of a bony bridge from the sacro-iliac joint and ligamentous ossifications to the spine. Early forms of the disease do not present such modifications to the sacro-iliac joint and therefore, show no visible sacroiliitis on conventional x-ray. Thus, it is possible to classify a patient aged <45 years with inflammatory lower back pain as having Ax-SpA, irrespective of the presence of sacroiliitis by x-ray. Indeed, inflammation of the sacro-iliac joint and spine occurs before the process of ossification and inflammation, and can be detected by MRI. This led the Assessment of SpondyloArthritis international Society (ASAS) group to propose candidate classification criteria for Ax-SpA, notably adapted to early forms of the disease. Accordingly, patients with Ax-SpA without radiographic sacroiliitis are considered to have non-radiographic Ax-SpA. Classification criteria for peripheral SpA are also available.
The determinants of AS and SpA are complex, and involve both genetic and environmental factors. In addition to these factors, several studies in recent years have also highlighted the emerging role of epigenetics in the pathophysiology of inflammatory diseases.
The term epigenetics refers to heritable and reversible modifications in gene expression without any change in the coding DNA sequence. This process may be involved in the pathophysiology of different diseases and their clinical expression. Several different epigenetic mechanisms may concur to modify gene functioning. Changes to the chromatin and to DNA (without modification of the encoding sequence itself) have been shown to be important for the control of gene expression through suppressive or permissive factors. Thus, DNA methylation could play a role in auto-immune or inflammatory diseases by regulating gene expression, particularly those coding for pro-inflammatory mediators such as certain cytokines, thereby contributing to dysregulation of the immune system.
DNA methylation is regulated by the activity of DNA methyltransferase enzymes (DNMT). In multicellular eukaryotic organisms, DNA methylation is associated with chromatin repression, and thereby, inhibition of gene expression. DNA methylation can be evaluated across the whole genome, but also at the level of a specific candidate gene, such as the gene encoding a pro-inflammatory cytokine.
The level of DNA methylation has been evaluated in rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE), and a "methylated-DNA" signature has been observed in these auto-immune diseases. Currently, there is no available data regarding DNA methylation in AS or SpA in general. In this study, the investigators aim to analyse the global DNA methylation in patients with AS or Ax-SpA.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patient group | Experimental | Other: Blood sampleSubjects must meet the modified New York criteria for AS, or the ASAS criteria for Ax-SpA, and must be naïve of biologic therapy (anti-TNF-α agents) at the time of inclusion, or have received but subsequently discontinued anti-TNF-α therapy at least 3 months before inclusion. A blood sample will be drawn (35 mL) to these patients. |
| Control group | Other | Other: Blood sampleSubjects must be free from any inflammatory or auto-immune disease. A blood sample will be drawn (35 mL) to these controls subjects. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects included in the Patient group must meet the modified New York criteria for AS, or the ASAS criteria for Ax-SpA, and must be naïve of biologic therapy (anti-TNF-α agents) at the time of inclusion, or have received but subsequently discontinued anti-TNF-α therapy at least 3 months before inclusion.
- Subjects included in the Control group must be free from any inflammatory or auto-immune disease. Subjects being followed for spinal disc disease (herniated disc) or abarticular mechanical disease (tendonitis) will be eligible, as well as healthy subjects.
- Adult patients (≥18 years).
- Provide written informed consent indicating that the subject has understood the aims of the study, as well as the procedures involved, and that he/she accepts to participate and adhere to the demands and restrictions imposed by the study participation.
- All subjects must have social security coverage.
Key exclusion criteria (7 listed)
- Subjects being treated by systemic corticosteroids with a prednisone equivalent dose >10 mg/day.
- Subjects with limited legal capacity.
- Subjects judged by the investigator to be unlikely to comply with study procedures
- Subjects with no social security coverage.
- Pregnant women.
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 |
|---|---|---|
| Blood sample35 mL, 7 tubes | Other | Control group, Patient group |
Primary outcome
Overall level of DNA methylation
Time frame: D0 (day of inclusion)
The level of methylation will be evaluated using the global quantification technique for DNA
3 secondary outcomes
Expression of DNMT1 and MBD2
Time frame: D0 (day of inclusion)
Methylation of the promoter region of TNF
Time frame: D0 (day of inclusion)
Serum TNF-α
Time frame: D0 (day of inclusion)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2021.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sample in people with Spondylitis, Ankylosing and Axial Spondyloarthritis, run by Centre Hospitalier Universitaire de Besancon at 1 site 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 7 inclusion and 7 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: finished, as of the sponsor's last update on 1 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall level of DNA methylation (time frame: D0 (day of inclusion)). 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 1 Feb 2021.