Rheumatoid ArthritisNCT03149796
Tocilizumab Effect on microRNA Expression and Adipokine Levels in Rheumatoid Arthritis Patients
An observational study of Rheumatoid Arthritis, run by Carmel Medical Center.
Trial summary
The investigators propose to identify changes in cytokines like adipocytokines and microRNA (miR) expression (for example miR-9, miR-16, miR-125, miR-132, miR-146a, miR-150, miR-155, miR-181 and miR-223) in peripheral blood leukocytes and in serum samples obtained from rheumatoid arthritis (RA) patients before and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- laboratory blood tests
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- 23 Mar 2011to 1 May 2013
- 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 18 years and older
- All sexes
- Adult, Older adult
Study population: RA patients treated with tocilizumab, according to the local clinical guidelines
Who may be able to join
- Patients fulfilling the 2010 Rheumatoid Arthritis Classification criteria.
- Patients designated to tocilizumab treatment
- Age above 18 years old
- Signed informed concern
- Ability to read and write in Hebrew
Who cannot join
- Patients with other rheumatic diseases
- Patients with other inflammatory diseases
- Patients with malignancies
About this study
Official title: The Effect of Tocilizumab (Anti-interleukin-6) Treatment on microRNA Expression and Adipokine Levels in Rheumatoid Arthritis Patients
The investigators propose to identify changes in cytokines like adipocytokines and microRNA (miR) expression (for example miR-9, miR-16, miR-125, miR-132, miR-146a, miR-150, miR-155, miR-181 and miR-223) in peripheral blood leukocytes and in serum samples obtained from rheumatoid arthritis (RA) patients before and after tocilizumab treatment. The results obtained will be compared to gender- and age-matched healthy controls, and will help the investigators define one or more miRNAs as biomarkers for treatment effectiveness.
Methods The investigators will obtain blood samples from 60 RA patients treated with tocilizumab, according to the local clinical guidelines. Blood samples will be collected before treatment, as well as one and four months following tocilizumab treatment. The blood samples will initially undergo microarray analysis and then the results will be confirmed for specific miRNAs by quantitative real-time PCR (qPCR). The serum level of the tested cytokines, like adipokines, will be measured using ELISA methods. The changes in cytokines level and miRNAs expression, either up-regulation or down-regulation, during tocilizumab therapy will be correlated to the severity of the disease and to specific demographic and medical data. The results obtained will be compared to 60 healthy controls gender- and age-matched
Read the detailed description
The aim of the study is to investigate the effects of tocilizumab on the expression of biomarkers like adipocytokines and miRNAs in peripheral blood leukocytes and in serum samples obtained from rheumatoid arthritis patients. Candidate miRNAs that are likely to be quantitated are for example miR-9, 16, 125, 132, 146a, 150, 155, 181 and, 223. The results obtained will help the investigators determine if cytokines and miRNAs expression can be used as a novel biomarker for the determination of the effectiveness of tocilizumab treatment.
The study is designed as a prospective study investigating the effect of tocilizumab on the expression of cytokines and miRNA in rheumatoid arthritis patients. Sixty rheumatoid arthritis patients designated to be treated with tocilizumab and followed in rheumatology clinics.
After receiving informed consent, three blood samples of 5cc blood each will be drawn: the first - before tocilizumab treatment to set the basal level of expression in untreated patients, the second and third samples will be taken one month and four months after initiation of tocilizumab treatment. The investigators will use selected samples (from 5 patients) to perform microarray analysis for miRNAs expression, and based on the results, we will confirm the expression of specific miRNAs by quantitative real-time PCR (qPCR). Based on current knowledge, the investigators expect that miR-9, 16, 125, 132, 146a, 150, 155, 181 and, 223 will show significant changes in expression upon tocilizumab treatment. Cytokines levels are measured using ELISA tests for each individual biomarker. The changes in cytokines and miRNAs expression, either up-regulation or down-regulation, will be correlated to the severity of the disease and to the clinical effect of tocilizumab. Information regarding disease duration, activity as measured by disease activity score, concomitant treatment and serology status will be collected. Also demographic characteristics - age, sex and smoking status will be recorded. The results will be compared to 60 healthy controls gender- and age matched, without any rheumatic, inflammatory or malignant disorders
- Conditions
- Rheumatoid Arthritis
- Being tested
- laboratory blood tests
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
laboratory blood testsOther
Serum concentrations of leptin, adiponectin, resistin, interleukin-6 and high sensitivity C reactive protein were measured by ELISA in both study groups
| Study group | Role | What they receive |
|---|---|---|
| RA patients | designated to be treated with tocilizumab and followed in rheumatology clinics.
Laboratory blood tests will be collected and analyzed Receives: Other: laboratory blood tests | |
| healthy controls | control Laboratory blood tests will be collected and analyzed Receives: Other: laboratory blood tests |
What is being measured
The primary outcome is the main question the study is designed to answer.
expression of biomarkers like adipocytokines and miRNAs
expression of biomarkers like adipocytokines and miRNAs in peripheral blood leukocytes and in serum samples obtained from RA patients. Candidate miRNAs that are likely to be quantitated are for example miR-9, 16, 125, 132, 146a, 150, 155, 181 and, 223
Measured: four months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2017
- Study start23 Mar 2011
- Primary completion1 May 2013
- Study completion1 May 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies 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-control
- Time perspective
- Retrospective
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carmel Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Devy Zissman, Carmel Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03149796
- Sponsor's protocol ID
- CMC-11-0018-CTIL
- Status last verified
- May 2017
- First submitted
- 10 May 2017
- Last updated
- 16 May 2017
- Results posted
- No
- Individual data sharing
- Yes
Publications
Barton A, Worthington J. Genetic susceptibility to rheumatoid arthritis: an emerging picture. Arthritis Rheum. 2009 Oct 15;61(10):1441-6. doi: 10.1002/art.24672. No abstract available.
PubMed 19790122Symmons D, Harrison B. Early inflammatory polyarthritis: results from the norfolk arthritis register with a review of the literature. I. Risk factors for the development of inflammatory polyarthritis and rheumatoid arthritis. Rheumatology (Oxford). 2000 Aug;39(8):835-43. doi: 10.1093/rheumatology/39.8.835. No abstract available.
PubMed 10952736Lard LR, Visser H, Speyer I, vander Horst-Bruinsma IE, Zwinderman AH, Breedveld FC, Hazes JM. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med. 2001 Oct 15;111(6):446-51. doi: 10.1016/s0002-9343(01)00872-5.
PubMed 11690569Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003 May 15;423(6937):356-61. doi: 10.1038/nature01661.
PubMed 12748655Redlich K, Hayer S, Ricci R, David JP, Tohidast-Akrad M, Kollias G, Steiner G, Smolen JS, Wagner EF, Schett G. Osteoclasts are essential for TNF-alpha-mediated joint destruction. J Clin Invest. 2002 Nov;110(10):1419-27. doi: 10.1172/JCI15582.
PubMed 12438440Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14:397-440. doi: 10.1146/annurev.immunol.14.1.397.
PubMed 8717520Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT, Martin TJ, Suda T. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999 May;103(9):1345-52. doi: 10.1172/JCI5703.
PubMed 10225978Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010 Jan;49(1):15-24. doi: 10.1093/rheumatology/kep329. Epub 2009 Oct 23.
PubMed 19854855Eastgate JA, Symons JA, Wood NC, Grinlinton FM, di Giovine FS, Duff GW. Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. Lancet. 1988 Sep 24;2(8613):706-9. doi: 10.1016/s0140-6736(88)90185-7.
PubMed 2901567van Leeuwen MA, Westra J, Limburg PC, van Riel PL, van Rijswijk MH. Clinical significance of interleukin-6 measurement in early rheumatoid arthritis: relation with laboratory and clinical variables and radiological progression in a three year prospective study. Ann Rheum Dis. 1995 Aug;54(8):674-7. doi: 10.1136/ard.54.8.674.
PubMed 7677445Taganov KD, Boldin MP, Baltimore D. MicroRNAs and immunity: tiny players in a big field. Immunity. 2007 Feb;26(2):133-7. doi: 10.1016/j.immuni.2007.02.005.
PubMed 17307699Shi XB, Tepper CG, deVere White RW. Cancerous miRNAs and their regulation. Cell Cycle. 2008 Jun 1;7(11):1529-38. doi: 10.4161/cc.7.11.5977. Epub 2008 Mar 20.
PubMed 18469525Williams AE, Perry MM, Moschos SA, Larner-Svensson HM, Lindsay MA. Role of miRNA-146a in the regulation of the innate immune response and cancer. Biochem Soc Trans. 2008 Dec;36(Pt 6):1211-5. doi: 10.1042/BST0361211.
PubMed 19021527Baltimore D, Boldin MP, O'Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008 Aug;9(8):839-45. doi: 10.1038/ni.f.209.
PubMed 18645592O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1604-9. doi: 10.1073/pnas.0610731104. Epub 2007 Jan 22.
PubMed 17242365
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Tocilizumab (Anti-interleukin-6) Treatment on microRNA Expression and Adipokine Levels in Rheumatoid Arthritis Patients
- ClinicalTrials.gov ID
- NCT03149796
- Acronym / sponsor ID
- CMC-11-0018-CTIL
- Conditions
- Rheumatoid Arthritis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Carmel Medical CenterUniversity, hospital or other
- Study start
- 23 Mar 2011 (actual)
- Primary completion
- 1 May 2013 (actual)
- Study completion
- 1 May 2013 (actual)
- First posted
- 11 May 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 investigators propose to identify changes in cytokines like adipocytokines and microRNA (miR) expression (for example miR-9, miR-16, miR-125, miR-132, miR-146a, miR-150, miR-155, miR-181 and miR-223) in peripheral blood leukocytes and in serum samples obtained from rheumatoid arthritis (RA) patients before and after tocilizumab treatment. The results obtained will be compared to gender- and age-matched healthy controls, and will help the investigators define one or more miRNAs as biomarkers for treatment effectiveness.
Methods The investigators will obtain blood samples from 60 RA patients treated with tocilizumab, according to the local clinical guidelines. Blood samples will be collected before treatment, as well as one and four months following tocilizumab treatment. The blood samples will initially undergo microarray analysis and then the results will be confirmed for specific miRNAs by quantitative real-time PCR (qPCR). The serum level of the tested cytokines, like adipokines, will be measured using ELISA methods. The changes in cytokines level and miRNAs expression, either up-regulation or down-regulation, during tocilizumab therapy will be correlated to the severity of the disease and to specific demographic and medical data. The results obtained will be compared to 60 healthy controls gender- and age-matched
Detailed description
The aim of the study is to investigate the effects of tocilizumab on the expression of biomarkers like adipocytokines and miRNAs in peripheral blood leukocytes and in serum samples obtained from rheumatoid arthritis patients. Candidate miRNAs that are likely to be quantitated are for example miR-9, 16, 125, 132, 146a, 150, 155, 181 and, 223. The results obtained will help the investigators determine if cytokines and miRNAs expression can be used as a novel biomarker for the determination of the effectiveness of tocilizumab treatment.
The study is designed as a prospective study investigating the effect of tocilizumab on the expression of cytokines and miRNA in rheumatoid arthritis patients. Sixty rheumatoid arthritis patients designated to be treated with tocilizumab and followed in rheumatology clinics.
After receiving informed consent, three blood samples of 5cc blood each will be drawn: the first - before tocilizumab treatment to set the basal level of expression in untreated patients, the second and third samples will be taken one month and four months after initiation of tocilizumab treatment. The investigators will use selected samples (from 5 patients) to perform microarray analysis for miRNAs expression, and based on the results, we will confirm the expression of specific miRNAs by quantitative real-time PCR (qPCR). Based on current knowledge, the investigators expect that miR-9, 16, 125, 132, 146a, 150, 155, 181 and, 223 will show significant changes in expression upon tocilizumab treatment. Cytokines levels are measured using ELISA tests for each individual biomarker. The changes in cytokines and miRNAs expression, either up-regulation or down-regulation, will be correlated to the severity of the disease and to the clinical effect of tocilizumab. Information regarding disease duration, activity as measured by disease activity score, concomitant treatment and serology status will be collected. Also demographic characteristics - age, sex and smoking status will be recorded. The results will be compared to 60 healthy controls gender- and age matched, without any rheumatic, inflammatory or malignant disorders
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RA patients | – | Other: laboratory blood testsdesignated to be treated with tocilizumab and followed in rheumatology clinics. Laboratory blood tests will be collected and analyzed |
| healthy controls | – | Other: laboratory blood testscontrol Laboratory blood tests will be collected and analyzed |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- RA patients treated with tocilizumab, according to the local clinical guidelines
Key inclusion criteria (5 listed)
- Patients fulfilling the 2010 Rheumatoid Arthritis Classification criteria.
- Patients designated to tocilizumab treatment
- Age above 18 years old
- Signed informed concern
- Ability to read and write in Hebrew
Key exclusion criteria (3 listed)
- Patients with other rheumatic diseases
- Patients with other inflammatory diseases
- Patients with malignancies
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 |
|---|---|---|
| laboratory blood testsSerum concentrations of leptin, adiponectin, resistin, interleukin-6 and high sensitivity C reactive protein were measured by ELISA in both study groups | Other | RA patients, healthy controls |
Primary outcome
expression of biomarkers like adipocytokines and miRNAs
Time frame: four months
expression of biomarkers like adipocytokines and miRNAs in peripheral blood leukocytes and in serum samples obtained from RA patients. Candidate miRNAs that are likely to be quantitated are for example miR-9, 16, 125, 132, 146a, 150, 155, 181 and, 223
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 16 May 2017.
- Background: PubMed 19790122Barton A, Worthington J. Genetic susceptibility to rheumatoid arthritis: an emerging picture. Arthritis Rheum. 2009 Oct 15;61(10):1441-6. doi: 10.1002/art.24672. No abstract available.
- Background: PubMed 10952736Symmons D, Harrison B. Early inflammatory polyarthritis: results from the norfolk arthritis register with a review of the literature. I. Risk factors for the development of inflammatory polyarthritis and rheumatoid arthritis. Rheumatology (Oxford). 2000 Aug;39(8):835-43. doi: 10.1093/rheumatology/39.8.835. No abstract available.
- Background: PubMed 11690569Lard LR, Visser H, Speyer I, vander Horst-Bruinsma IE, Zwinderman AH, Breedveld FC, Hazes JM. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med. 2001 Oct 15;111(6):446-51. doi: 10.1016/s0002-9343(01)00872-5.
- Background: PubMed 12748655Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003 May 15;423(6937):356-61. doi: 10.1038/nature01661.
- Background: PubMed 12438440Redlich K, Hayer S, Ricci R, David JP, Tohidast-Akrad M, Kollias G, Steiner G, Smolen JS, Wagner EF, Schett G. Osteoclasts are essential for TNF-alpha-mediated joint destruction. J Clin Invest. 2002 Nov;110(10):1419-27. doi: 10.1172/JCI15582.
- Background: PubMed 8717520Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14:397-440. doi: 10.1146/annurev.immunol.14.1.397.
- Background: PubMed 10225978Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT, Martin TJ, Suda T. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999 May;103(9):1345-52. doi: 10.1172/JCI5703.
- Background: PubMed 19854855Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010 Jan;49(1):15-24. doi: 10.1093/rheumatology/kep329. Epub 2009 Oct 23.
- Background: PubMed 2901567Eastgate JA, Symons JA, Wood NC, Grinlinton FM, di Giovine FS, Duff GW. Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. Lancet. 1988 Sep 24;2(8613):706-9. doi: 10.1016/s0140-6736(88)90185-7.
- Background: PubMed 7677445van Leeuwen MA, Westra J, Limburg PC, van Riel PL, van Rijswijk MH. Clinical significance of interleukin-6 measurement in early rheumatoid arthritis: relation with laboratory and clinical variables and radiological progression in a three year prospective study. Ann Rheum Dis. 1995 Aug;54(8):674-7. doi: 10.1136/ard.54.8.674.
- Background: PubMed 17307699Taganov KD, Boldin MP, Baltimore D. MicroRNAs and immunity: tiny players in a big field. Immunity. 2007 Feb;26(2):133-7. doi: 10.1016/j.immuni.2007.02.005.
- Background: PubMed 18469525Shi XB, Tepper CG, deVere White RW. Cancerous miRNAs and their regulation. Cell Cycle. 2008 Jun 1;7(11):1529-38. doi: 10.4161/cc.7.11.5977. Epub 2008 Mar 20.
- Individual participant dataSharing planned: Yes
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatoid Arthritis, run by Carmel Medical Center.
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 5 inclusion and 3 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 16 May 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?
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?
expression of biomarkers like adipocytokines and miRNAs (time frame: four months). 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 NCT03149796, which also lists 22 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 16 May 2017.