Tocilizumab Effect on microRNA Expression and Adipokine Levels in Rheumatoid Arthritis Patients

Rheumatoid Arthritis Clinical Trial

Official title:

The Effect of Tocilizumab (Anti-interleukin-6) Treatment on microRNA Expression and Adipokine Levels in Rheumatoid Arthritis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03149796
• Other study ID #: CMC-11-0018-CTIL
• Status: Completed
• Phase: N/A
• First received: May 10, 2017
• Last updated: May 14, 2017
• Start date: March 23, 2011
• Est. completion date: May 1, 2013

Study information

• Verified date: May 2017
• Source: Carmel Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: May 1, 2013
• Est. primary completion date: May 1, 2013
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Patients with other rheumatic diseases

• Patients with other inflammatory diseases

• Patients with malignancies

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Other:
• laboratory blood tests
Serum concentrations of leptin, adiponectin, resistin, interleukin-6 and high sensitivity C reactive protein were measured by ELISA in both study groups

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Carmel Medical Center

References & Publications (22)

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Rho YH, Solus J, Sokka T, Oeser A, Chung CP, Gebretsadik T, Shintani A, Pincus T, Stein CM. Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis. Arthritis Rheum. 2009 Jul;60(7):1906-14. doi: 10.1002/art.24626. — View Citation

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Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12481-6. Epub 2006 Aug 2. — View Citation

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	four months