Rheumatoid ArthritisNCT04092244
Role of CTHRC1 in Diagnosis of Rheumatoid Arthritis
An observational study of Rheumatoid Arthritis, run by Assiut University.
Trial summary
to detect the role of CTHRC1 biomarker in diagnosis of rheumatoid arthritis and To correlate other well-established rheumatoid arthritis markers (RF\& anti-ccp) and CTHRC1 level to see if CTHRC1 can act as a dependent or independent serum marker in prediction of RA status. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- CTHRC1 biomarker
- How many people
- 90 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2020to 30 Dec 2021
- 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 Any age
- All sexes
- Child, Adult, Older adult
Study population: The study will include the following: * 35 RA patients with negative anti_ccp. * 35 RA patients with negative RF. * 45 RA patients either positive RF or anti-ccp. * 30 other Arthritic patients. * 25 healthy controls.
Who may be able to join
- All RA patients must fulfill the 2010 ACR/EULAR criteria for RA.
- Healthy individual must be without a prior history of chronic inflammation or any form of arthritis.
Who cannot join
- - Patients with solid tumors.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: CTHRC1 as a New Biomarker in Diagnosis of Rheumatoid Arthritis and Its Role in Seronegative Patients.
to detect the role of CTHRC1 biomarker in diagnosis of rheumatoid arthritis and To correlate other well-established rheumatoid arthritis markers (RF\& anti-ccp) and CTHRC1 level to see if CTHRC1 can act as a dependent or independent serum marker in prediction of RA status.
Read the detailed description
Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease of synovial joints. Disease progression is characterized by periods of high disease activity involving both, a systemic immune response and tissue-specific inflammatory events that may lead to joint and bone destruction and subsequent disability.
Rheumatoid arthritis is a multifactorial disease with significant contribution from genetic and non-genetic factors that together account for complex disease pathology.
Diagnosis of RA is based mainly on detection of high titers of rheumatoid factor (RF) and of antibodies against cyclic citrullinated peptide (anti-CCP) or against citrullinated protein (ACPA).
The major RF species could be detected only in 60-70% of RA patients; patients with high levels of RF have higher disease activity with greater disabilities.
The problem is that RF is not a specific marker for RA and is often absent in early stages of the disease, on the other hand ACPA and CCP auto antibodies provide high specificity but moderate sensitivity, adding to that CRP and ESR are general indicators of inflammation and are not specific for RA.
Collagen triple helix repeat containing 1 protein (CTHRC1) is expressed in a number of embryonic and neonate tissues, including developing cartilage and bone. It is a secreted modulator of Wnt signaling, which is a key regulator of joint remodeling and promotes cell proliferation and migration.
Immunohistochemical analysis of various human primary cancers and metastases has revealed that CTHRC1 expression is actually limited to the stromal cells of solid tumors.
The expression of CTHRC1 encoding gene was found to be strongly associated with the severity of murine collagen antibody-induced arthritis.
Arthritic pannus is a multicellular vascularized tissue composed of cells of both mesenchymal and hematopoietic origin, including synovial fibroblasts, osteoclasts, endothelial cells, dendritic cells, monocytes/macrophages, as well as T and B cells that contribute to the development and progression of joint and cartilage erosion through secretion of pro-inflammatory cytokines and tissue-degrading proteases. Fibroblast-like synoviocytes (FLS), particularly the invasive and migratory cadherin-11-positive subtype, are major components of synovial pannus tissue and are considered active drivers in the pathogenesis of RA.
The expression of CTHRC1 in pannus and its role in the function of FLS relevant to cartilage damage in RA make it of great value if used as a blood-based biomarker for improved diagnosis of rheumatoid arthritis patients.
- Conditions
- Rheumatoid Arthritis
- Being tested
- CTHRC1 biomarker
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTHRC1 biomarkerDiagnostic test
its a biomarker detected in the serum of the patients
What is being measured
The primary outcome is the main question the study is designed to answer.
detect value of CTHRC1 in diagnosis of rheumatoid arthritis
detect the role of CTHRC1 biomarker in diagnosis of rheumatoid arthritis and To compare the sensitivity and the specificity of CTHRC1 in relation to other biomarkers used in diagnosis of RA.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2019
- Study start1 Aug 2020 (estimated)
- Primary completion28 Nov 2021 (estimated)
- Study completion30 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)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
- Retrospective
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amany Abdelkader Ahmed Hefny, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04092244
- Sponsor's protocol ID
- CTHRC1 in rheumatoid disease
- Status last verified
- May 2020
- First submitted
- 15 Sep 2019
- Last updated
- 28 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K. Rheumatoid arthritis. Nat Rev Dis Primers. 2018 Feb 8;4:18001. doi: 10.1038/nrdp.2018.1.
PubMed 29417936Shekhani MT, Forde TS, Adilbayeva A, Ramez M, Myngbay A, Bexeitov Y, Lindner V, Adarichev VA. Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus. Arthritis Res Ther. 2016 Jul 19;18:171. doi: 10.1186/s13075-016-1067-1.
PubMed 27430622Song YW, Kang EH. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM. 2010 Mar;103(3):139-46. doi: 10.1093/qjmed/hcp165. Epub 2009 Nov 19.
PubMed 19926660Singal DP, Li J, Zhu Y. Genetic basis for rheumatoid arthritis. Arch Immunol Ther Exp (Warsz). 1999;47(5):307-11.
PubMed 10604236Nell VP, Machold KP, Stamm TA, Eberl G, Heinzl H, Uffmann M, Smolen JS, Steiner G. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis. 2005 Dec;64(12):1731-6. doi: 10.1136/ard.2005.035691. Epub 2005 May 5.
PubMed 15878904Lefevre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, Korb A, Schnaker EM, Tarner IH, Robbins PD, Evans CH, Sturz H, Steinmeyer J, Gay S, Scholmerich J, Pap T, Muller-Ladner U, Neumann E. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med. 2009 Dec;15(12):1414-20. doi: 10.1038/nm.2050. Epub 2009 Nov 8.
PubMed 19898488Han B, Pouget JG, Slowikowski K, Stahl E, Lee CH, Diogo D, Hu X, Park YR, Kim E, Gregersen PK, Dahlqvist SR, Worthington J, Martin J, Eyre S, Klareskog L, Huizinga T, Chen WM, Onengut-Gumuscu S, Rich SS; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Wray NR, Raychaudhuri S. A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases. Nat Genet. 2016 Jul;48(7):803-10. doi: 10.1038/ng.3572. Epub 2016 May 16.
PubMed 27182969Durmus T, LeClair RJ, Park KS, Terzic A, Yoon JK, Lindner V. Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1). Gene Expr Patterns. 2006 Oct;6(8):935-40. doi: 10.1016/j.modgep.2006.03.008. Epub 2006 Mar 17.
PubMed 16678498Ding B, Padyukov L, Lundstrom E, Seielstad M, Plenge RM, Oksenberg JR, Gregersen PK, Alfredsson L, Klareskog L. Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region. Arthritis Rheum. 2009 Jan;60(1):30-8. doi: 10.1002/art.24135.
PubMed 19116921
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CTHRC1 as a New Biomarker in Diagnosis of Rheumatoid Arthritis and Its Role in Seronegative Patients.
- ClinicalTrials.gov ID
- NCT04092244
- Acronym / sponsor ID
- CTHRC1 in rheumatoid disease
- Conditions
- Rheumatoid Arthritis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Aug 2020 (estimated)
- Primary completion
- 28 Nov 2021 (estimated)
- Study completion
- 30 Dec 2021 (estimated)
- First posted
- 17 Sep 2019 (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.
to detect the role of CTHRC1 biomarker in diagnosis of rheumatoid arthritis and To correlate other well-established rheumatoid arthritis markers (RF\& anti-ccp) and CTHRC1 level to see if CTHRC1 can act as a dependent or independent serum marker in prediction of RA status.
Detailed description
Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease of synovial joints. Disease progression is characterized by periods of high disease activity involving both, a systemic immune response and tissue-specific inflammatory events that may lead to joint and bone destruction and subsequent disability.
Rheumatoid arthritis is a multifactorial disease with significant contribution from genetic and non-genetic factors that together account for complex disease pathology.
Diagnosis of RA is based mainly on detection of high titers of rheumatoid factor (RF) and of antibodies against cyclic citrullinated peptide (anti-CCP) or against citrullinated protein (ACPA).
The major RF species could be detected only in 60-70% of RA patients; patients with high levels of RF have higher disease activity with greater disabilities.
The problem is that RF is not a specific marker for RA and is often absent in early stages of the disease, on the other hand ACPA and CCP auto antibodies provide high specificity but moderate sensitivity, adding to that CRP and ESR are general indicators of inflammation and are not specific for RA.
Collagen triple helix repeat containing 1 protein (CTHRC1) is expressed in a number of embryonic and neonate tissues, including developing cartilage and bone. It is a secreted modulator of Wnt signaling, which is a key regulator of joint remodeling and promotes cell proliferation and migration.
Immunohistochemical analysis of various human primary cancers and metastases has revealed that CTHRC1 expression is actually limited to the stromal cells of solid tumors.
The expression of CTHRC1 encoding gene was found to be strongly associated with the severity of murine collagen antibody-induced arthritis.
Arthritic pannus is a multicellular vascularized tissue composed of cells of both mesenchymal and hematopoietic origin, including synovial fibroblasts, osteoclasts, endothelial cells, dendritic cells, monocytes/macrophages, as well as T and B cells that contribute to the development and progression of joint and cartilage erosion through secretion of pro-inflammatory cytokines and tissue-degrading proteases. Fibroblast-like synoviocytes (FLS), particularly the invasive and migratory cadherin-11-positive subtype, are major components of synovial pannus tissue and are considered active drivers in the pathogenesis of RA.
The expression of CTHRC1 in pannus and its role in the function of FLS relevant to cartilage damage in RA make it of great value if used as a blood-based biomarker for improved diagnosis of rheumatoid arthritis patients.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Age groups
- Child, Adult, Older adult
- Study population
- The study will include the following: * 35 RA patients with negative anti_ccp. * 35 RA patients with negative RF. * 45 RA patients either positive RF or anti-ccp. * 30 other Arthritic patients. * 25 healthy controls.
Key inclusion criteria (2 listed)
- All RA patients must fulfill the 2010 ACR/EULAR criteria for RA.
- Healthy individual must be without a prior history of chronic inflammation or any form of arthritis.
Key exclusion criteria (1 listed)
- - Patients with solid tumors.
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 |
|---|---|---|
| CTHRC1 biomarkerits a biomarker detected in the serum of the patients | Diagnostic test | – |
Primary outcome
detect value of CTHRC1 in diagnosis of rheumatoid arthritis
Time frame: baseline
detect the role of CTHRC1 biomarker in diagnosis of rheumatoid arthritis and To compare the sensitivity and the specificity of CTHRC1 in relation to other biomarkers used in diagnosis of RA.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2020.
- Background: PubMed 29417936Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K. Rheumatoid arthritis. Nat Rev Dis Primers. 2018 Feb 8;4:18001. doi: 10.1038/nrdp.2018.1.
- Background: PubMed 27430622Shekhani MT, Forde TS, Adilbayeva A, Ramez M, Myngbay A, Bexeitov Y, Lindner V, Adarichev VA. Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus. Arthritis Res Ther. 2016 Jul 19;18:171. doi: 10.1186/s13075-016-1067-1.
- Background: PubMed 19926660Song YW, Kang EH. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM. 2010 Mar;103(3):139-46. doi: 10.1093/qjmed/hcp165. Epub 2009 Nov 19.
- Background: PubMed 10604236Singal DP, Li J, Zhu Y. Genetic basis for rheumatoid arthritis. Arch Immunol Ther Exp (Warsz). 1999;47(5):307-11.
- Background: PubMed 15878904Nell VP, Machold KP, Stamm TA, Eberl G, Heinzl H, Uffmann M, Smolen JS, Steiner G. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis. 2005 Dec;64(12):1731-6. doi: 10.1136/ard.2005.035691. Epub 2005 May 5.
- Background: PubMed 19898488Lefevre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, Korb A, Schnaker EM, Tarner IH, Robbins PD, Evans CH, Sturz H, Steinmeyer J, Gay S, Scholmerich J, Pap T, Muller-Ladner U, Neumann E. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med. 2009 Dec;15(12):1414-20. doi: 10.1038/nm.2050. Epub 2009 Nov 8.
- Background: PubMed 27182969Han B, Pouget JG, Slowikowski K, Stahl E, Lee CH, Diogo D, Hu X, Park YR, Kim E, Gregersen PK, Dahlqvist SR, Worthington J, Martin J, Eyre S, Klareskog L, Huizinga T, Chen WM, Onengut-Gumuscu S, Rich SS; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Wray NR, Raychaudhuri S. A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases. Nat Genet. 2016 Jul;48(7):803-10. doi: 10.1038/ng.3572. Epub 2016 May 16.
- Background: PubMed 16678498Durmus T, LeClair RJ, Park KS, Terzic A, Yoon JK, Lindner V. Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1). Gene Expr Patterns. 2006 Oct;6(8):935-40. doi: 10.1016/j.modgep.2006.03.008. Epub 2006 Mar 17.
- Background: PubMed 19116921Ding B, Padyukov L, Lundstrom E, Seielstad M, Plenge RM, Oksenberg JR, Gregersen PK, Alfredsson L, Klareskog L. Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region. Arthritis Rheum. 2009 Jan;60(1):30-8. doi: 10.1002/art.24135.
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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 2 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 28 May 2020. 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 amany hefny (+201001545631, amany011108@med.aun.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
detect value of CTHRC1 in diagnosis of rheumatoid arthritis (time frame: baseline). 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 NCT04092244, which also lists 9 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 28 May 2020.