Rheumatoid ArthritisNCT03224377
Diagnostic Utility of Anti MCV Antibodies,Anti CCPantibodies and RF in RA
An observational study of Rheumatoid Arthritis, run by Assiut University.
Trial summary
Rheumatoid arthritis (RA) is a chronic systemic disease affecting primarily the synovium, leading to joint damage and bone destruction(Gravallese E,2002). It is probably the most common autoimmune disease, It is three times more common in women compared to men and usually appears in middle age(poulsom and charles… Read more about this study
- Who is it for?
- Ages 20 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- anti mutated citrullinated vimentin antibodies
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- 9 Oct 2017to 1 Feb 2019
- Phase
- Observational
- 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 20 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 80 patient with different rheumatic diseases,40 patients with RA and 20 patients with other rheumatic diseases (disease control),beside 20 healthy subject age and sex matched with the patients as healthy control. The patients will be recruited from Internal medicine department and Rheumatology Out patient clinics of Assuit University Hospital . All patients will be diagnosed as RA according to 2010 ACR/EULAR rheumatoid arthritis classification criteria.All patients will under go detailed history and compelete examination Generalized muscloskeletal examination and local clinical examination of affected joints e.g number of swollen joints ,number of tender joints,assessment of disease activity and functional disability by 28 joint disease activity score calculator (DAS28).
Who may be able to join
- patients with RA Patients with SLE,Psoriasis and systemic sclerosis as disease control
Who cannot join
- 1-malignancy patients 2-chronic infection patients as TB and Hepatitis B\&C 3_mixed connective tissue diseases
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Diagnostic Utility of Anti-mutated Citrullinated Vimentin Antibodies,Anti Cyclic Citrullinated Peptide Antibodies and Rheumatoid Factor in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic systemic disease affecting primarily the synovium, leading to joint damage and bone destruction(Gravallese E,2002). It is probably the most common autoimmune disease, It is three times more common in women compared to men and usually appears in middle age(poulsom and charles, 2016) .Early diagnosis of RA and its early treatment with disease-modifying anti rheumatic drugs lead to better control and less joint damage .therefore,It is very important to find an acceptable serological marker in order to make an early diagnosis and initiate early treatment to avoid complication and disability ( Orozco C,and Olsen,2006)
Various serum biomarkers are used to diagnose RA, including many autoantibodies. However, only rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) antibodies have wide acceptance (taylor et 2011).
Read the detailed description
Antibodies targeting citrullinated proteins are found to be highly specific for the diagnosis of RA (Riedmannet al,2005). Citrullinated antigens are thought to play a pivotal role in the pathogenesis of RA as they are expressed in inflamed joints and, anti-citrullinated protein antibodies are present before clinical disease and are highly specific for RA(van Gaalen et al,2005).
These autoantibodies predict clinical and radiological severity and may be implicated in the pathogenesis of RA ;however, they have a high value in the early diagnosis and early treatment of RA ( Agrawal et al ,2007).
Indeed, it has been demonstrated that anti-citrullinated protein antibodies are produced by plasma cells in the synovial tissue, as concentrations are more than seven fold higher in synovial tissue than in serum (Masson et al,2000).
Rheumatoid factor is not specific to RA, as it is present in patients suffering from other autoimmune and infectious diseases, also found in apparently healthy elderly patients(urusm et al, 2008). Anti- CCP has been shown to be a specific prognostic marker for RA and predict the erosive or non-erosive progression of the disease. Overall, anti-CCP antibodies are a useful marker for aiding the diagnosis of early RA, especially in seronegative(RF negative)( poulsom and charles,2007) Thus, it is a useful tool for the optimal therapeutic management of RA patients.
The diagnosis of RA has been improved by the introduction of other standardized immunoassays for the detection of auto-antibodies against different citrullinated antigens as anti-mutated citrullinated vimentin antibodies .Anti-MCV antibodies have been recommended to be better diagnostic marker for early arthritis (Luime et al,2010). Vimentin is an intermediate filament that is widely expressed by mesenchymal cells \&Macrophages and easy to detect in the synovium. Modification of the protein occurs in macrophages undergoing apoptosis, and antibodies to citrullinated vimentin may emerge if the apoptotic material inadequately cleared(Khalifa et ai 2013).
A significant correlation has been established between anti-MCV antibodies titers and both the severity of RA and the disease-activity score (DAS28) ,anti-MCV-positive patients exhibited significantly lower reduction in disease activity and a greater number of swollen joints. Thus, it appears that, anti-MCV antibodies may have the advantage of correlating better with disease activity and patient outcome(Al-Shukaili et al,2012)
The anti-mutated citrullinated vimentin antibody ELISA isa recently developed assay for the detection of IgG antibodies to a vimentin-based peptide .Anti-MCV antibody has been reported with a sensitivity of 65-82%, specificity of 80-95%.Anti-MCV antibody concentrations have also been reported as correlating with disease activity score , prognostic for disease severity, and being treatment sensitive, enabling their use in monitoring response to therapy (Bang et al,2006)
- Conditions
- Rheumatoid Arthritis
- Being tested
- anti mutated citrullinated vimentin antibodies
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti mutated citrullinated vimentin antibodiesDiagnostic test
Also called anti cyclic citrullinated peptide antibodies
Blood sampling using ELisa technique
| Study group | Role | What they receive |
|---|---|---|
| rheumatoid arthritis patients | Complete blood count Esr Crp Liver function test Kidney function test Hepatitis markers Rheumatoid factor Urine analysis Anti cyclic citrullinated peptide antibodies Anti mutated citrullinated vimentin antibodies Receives: Diagnostic Test: anti mutated citrullinated vimentin antibodies | |
| healthy control | Complete blood count Esr Crp Liver function test Kidney function test Hepatitis markers Rheumatoid factor Urine analysis Anti cyclic citrullinated peptide antibodies Anti mutated citrullinated vimentin antibodies Receives: Diagnostic Test: anti mutated citrullinated vimentin antibodies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti mutated citrullinated vimentin antibodies
blood sample using Elisa technique
Measured: at one day of the study
Anti cyclic citrullinated peptide antibodies
blood sample using Elisa technique
Measured: at one day of the study
Secondary outcomes (1)
rheumatoid factor (RF) antibody
blood sampling
Measured: at one day of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start9 Oct 2017 (estimated)
- Primary completion9 Oct 2018 (estimated)
- Study completion1 Feb 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ayat salah, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03224377
- Sponsor's protocol ID
- ASA
- Status last verified
- Jul 2017
- First submitted
- 19 Jul 2017
- Last updated
- 21 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Agrawal S, Misra R, Aggarwal A. Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA. Clin Rheumatol. 2007 Feb;26(2):201-4. doi: 10.1007/s10067-006-0275-5. Epub 2006 Mar 30.
PubMed 16572283Hayem G, Chazerain P, Combe B, Elias A, Haim T, Nicaise P, Benali K, Eliaou JF, Kahn MF, Sany J, Meyer O. Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthritis. J Rheumatol. 1999 Jan;26(1):7-13.
PubMed 9918234Orozco C, Olsen NJ. Identification of patients with early rheumatoid arthritis: challenges and future directions. Clin Dev Immunol. 2006 Jun-Dec;13(2-4):295-7. doi: 10.1080/17402520600877794.
PubMed 17162371Poulsom H, Charles PJ. Antibodies to citrullinated vimentin are a specific and sensitive marker for the diagnosis of rheumatoid arthritis. Clin Rev Allergy Immunol. 2008 Feb;34(1):4-10. doi: 10.1007/s12016-007-8016-3.
PubMed 18270850Riedemann JP, Munoz S, Kavanaugh A. The use of second generation anti-CCP antibody (anti-CCP2) testing in rheumatoid arthritis--a systematic review. Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S69-76.
PubMed 16273788Ursum J, Nielen MM, van Schaardenburg D, van der Horst AR, van de Stadt RJ, Dijkmans BA, Hamann D. Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study. Arthritis Res Ther. 2008;10(1):R12. doi: 10.1186/ar2362. Epub 2008 Jan 28.
PubMed 18226202van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998 Oct;41(10):1845-50. doi: 10.1002/1529-0131(199810)41:103.0.CO;2-K.
PubMed 9778226Vossenaar ER, Radstake TR, van der Heijden A, van Mansum MA, Dieteren C, de Rooij DJ, Barrera P, Zendman AJ, van Venrooij WJ. Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Ann Rheum Dis. 2004 Apr;63(4):373-81. doi: 10.1136/ard.2003.012211.
PubMed 15020330
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnostic Utility of Anti-mutated Citrullinated Vimentin Antibodies,Anti Cyclic Citrullinated Peptide Antibodies and Rheumatoid Factor in Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT03224377
- Acronym / sponsor ID
- ASA
- Conditions
- Rheumatoid Arthritis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 9 Oct 2017 (estimated)
- Primary completion
- 9 Oct 2018 (estimated)
- Study completion
- 1 Feb 2019 (estimated)
- First posted
- 21 Jul 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.
Rheumatoid arthritis (RA) is a chronic systemic disease affecting primarily the synovium, leading to joint damage and bone destruction(Gravallese E,2002). It is probably the most common autoimmune disease, It is three times more common in women compared to men and usually appears in middle age(poulsom and charles, 2016) .Early diagnosis of RA and its early treatment with disease-modifying anti rheumatic drugs lead to better control and less joint damage .therefore,It is very important to find an acceptable serological marker in order to make an early diagnosis and initiate early treatment to avoid complication and disability ( Orozco C,and Olsen,2006)
Various serum biomarkers are used to diagnose RA, including many autoantibodies. However, only rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) antibodies have wide acceptance (taylor et 2011).
Detailed description
Antibodies targeting citrullinated proteins are found to be highly specific for the diagnosis of RA (Riedmannet al,2005). Citrullinated antigens are thought to play a pivotal role in the pathogenesis of RA as they are expressed in inflamed joints and, anti-citrullinated protein antibodies are present before clinical disease and are highly specific for RA(van Gaalen et al,2005).
These autoantibodies predict clinical and radiological severity and may be implicated in the pathogenesis of RA ;however, they have a high value in the early diagnosis and early treatment of RA ( Agrawal et al ,2007).
Indeed, it has been demonstrated that anti-citrullinated protein antibodies are produced by plasma cells in the synovial tissue, as concentrations are more than seven fold higher in synovial tissue than in serum (Masson et al,2000).
Rheumatoid factor is not specific to RA, as it is present in patients suffering from other autoimmune and infectious diseases, also found in apparently healthy elderly patients(urusm et al, 2008). Anti- CCP has been shown to be a specific prognostic marker for RA and predict the erosive or non-erosive progression of the disease. Overall, anti-CCP antibodies are a useful marker for aiding the diagnosis of early RA, especially in seronegative(RF negative)( poulsom and charles,2007) Thus, it is a useful tool for the optimal therapeutic management of RA patients.
The diagnosis of RA has been improved by the introduction of other standardized immunoassays for the detection of auto-antibodies against different citrullinated antigens as anti-mutated citrullinated vimentin antibodies .Anti-MCV antibodies have been recommended to be better diagnostic marker for early arthritis (Luime et al,2010). Vimentin is an intermediate filament that is widely expressed by mesenchymal cells \&Macrophages and easy to detect in the synovium. Modification of the protein occurs in macrophages undergoing apoptosis, and antibodies to citrullinated vimentin may emerge if the apoptotic material inadequately cleared(Khalifa et ai 2013).
A significant correlation has been established between anti-MCV antibodies titers and both the severity of RA and the disease-activity score (DAS28) ,anti-MCV-positive patients exhibited significantly lower reduction in disease activity and a greater number of swollen joints. Thus, it appears that, anti-MCV antibodies may have the advantage of correlating better with disease activity and patient outcome(Al-Shukaili et al,2012)
The anti-mutated citrullinated vimentin antibody ELISA isa recently developed assay for the detection of IgG antibodies to a vimentin-based peptide .Anti-MCV antibody has been reported with a sensitivity of 65-82%, specificity of 80-95%.Anti-MCV antibody concentrations have also been reported as correlating with disease activity score , prognostic for disease severity, and being treatment sensitive, enabling their use in monitoring response to therapy (Bang et al,2006)
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rheumatoid arthritis patients | – | Diagnostic Test: anti mutated citrullinated vimentin antibodiesComplete blood count Esr Crp Liver function test Kidney function test Hepatitis markers Rheumatoid factor Urine analysis Anti cyclic citrullinated peptide antibodies Anti mutated citrullinated vimentin antibodies |
| healthy control | – | Diagnostic Test: anti mutated citrullinated vimentin antibodiesComplete blood count Esr Crp Liver function test Kidney function test Hepatitis markers Rheumatoid factor Urine analysis Anti cyclic citrullinated peptide antibodies Anti mutated citrullinated vimentin antibodies |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 80 patient with different rheumatic diseases,40 patients with RA and 20 patients with other rheumatic diseases (disease control),beside 20 healthy subject age and sex matched with the patients as healthy control. The patients will be recruited from Internal medicine department and Rheumatology Out patient clinics of Assuit University Hospital . All patients will be diagnosed as RA according to 2010 ACR/EULAR rheumatoid arthritis classification criteria.All patients will under go detailed history and compelete examination Generalized muscloskeletal examination and local clinical examination of affected joints e.g number of swollen joints ,number of tender joints,assessment of disease activity and functional disability by 28 joint disease activity score calculator (DAS28).
Key inclusion criteria (1 listed)
- patients with RA Patients with SLE,Psoriasis and systemic sclerosis as disease control
Key exclusion criteria (1 listed)
- 1-malignancy patients 2-chronic infection patients as TB and Hepatitis B\&C 3_mixed connective tissue diseases
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 |
|---|---|---|
| anti mutated citrullinated vimentin antibodiesAlso: anti cyclic citrullinated peptide antibodiesBlood sampling using ELisa technique | Diagnostic test | healthy control, rheumatoid arthritis patients |
Primary outcome
Anti mutated citrullinated vimentin antibodies
Time frame: at one day of the study
blood sample using Elisa technique
Anti cyclic citrullinated peptide antibodies
Time frame: at one day of the study
blood sample using Elisa technique
1 secondary outcome
rheumatoid factor (RF) antibody
Time frame: at one day of the study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2017.
- Results publication: PubMed 16572283Agrawal S, Misra R, Aggarwal A. Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA. Clin Rheumatol. 2007 Feb;26(2):201-4. doi: 10.1007/s10067-006-0275-5. Epub 2006 Mar 30.
- Results publication: PubMed 9918234Hayem G, Chazerain P, Combe B, Elias A, Haim T, Nicaise P, Benali K, Eliaou JF, Kahn MF, Sany J, Meyer O. Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthritis. J Rheumatol. 1999 Jan;26(1):7-13.
- Results publication: PubMed 17162371Orozco C, Olsen NJ. Identification of patients with early rheumatoid arthritis: challenges and future directions. Clin Dev Immunol. 2006 Jun-Dec;13(2-4):295-7. doi: 10.1080/17402520600877794.
- Results publication: PubMed 18270850Poulsom H, Charles PJ. Antibodies to citrullinated vimentin are a specific and sensitive marker for the diagnosis of rheumatoid arthritis. Clin Rev Allergy Immunol. 2008 Feb;34(1):4-10. doi: 10.1007/s12016-007-8016-3.
- Results publication: PubMed 16273788Riedemann JP, Munoz S, Kavanaugh A. The use of second generation anti-CCP antibody (anti-CCP2) testing in rheumatoid arthritis--a systematic review. Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S69-76.
- Results publication: PubMed 18226202Ursum J, Nielen MM, van Schaardenburg D, van der Horst AR, van de Stadt RJ, Dijkmans BA, Hamann D. Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study. Arthritis Res Ther. 2008;10(1):R12. doi: 10.1186/ar2362. Epub 2008 Jan 28.
- Results publication: PubMed 9778226van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998 Oct;41(10):1845-50. doi: 10.1002/1529-0131(199810)41:103.0.CO;2-K.
- Results publication: PubMed 15020330Vossenaar ER, Radstake TR, van der Heijden A, van Mansum MA, Dieteren C, de Rooij DJ, Barrera P, Zendman AJ, van Venrooij WJ. Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Ann Rheum Dis. 2004 Apr;63(4):373-81. doi: 10.1136/ard.2003.012211.
- 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.
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatoid Arthritis, run by Assiut University.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 21 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nabawia M Tawfik, MD (0122 397 1418, nabawia.hassan@med.au.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anti mutated citrullinated vimentin antibodies (time frame: at one day of the study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03224377, which also lists 8 linked publications.
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 21 Jul 2017.