Circulating microRNAs as Novel Prognosis Biomarkers for Rheumatoid Arthritis

Circulating microRNAs Expression as Predictors of Clinical Response in Rheumatoid Arthritis Patients Treated With Green Tea

The correlation of circulating serum miR-125ba and miR-146a expression and clinical response to green tea therapy were analysed in RA patients.Clinical response to green tea therapy for 24 weeks was calculated from DAS28 scores. Whereas , a decrease of 1.2 points or above in DAS28 scores at 24 weeks of treatment compared with baseline was defined as clinical response according to the EULAR response criteria.A ready-made solutions containing the primers and probes for human miR-146a and miR-125ba (Applied Biosystems, Foster City, CA) and real-time RT-PCR was estimated using an ABI 7300 system (Applied Bio systems).

Study Overview

• Status: Completed
• Conditions: Rh Disease
• Intervention / Treatment: Dietary supplement: Green tea group

Detailed Description

1. participants: A total of 100 subjects (aged 18-65 years) who were diagnosed as RA with moderate to severe activity at the division of rheumatology and clinical immunology at Mansoura University were evaluated in this study.
2. patients were evaluated for therapeutic response at baseline and 12, and 24 weeks of green tea therapy. All patients with RA were subjected for estimation of ESR, CRP, disease activity score in 28 joints (DAS28), patient's global assessment (PGA), and health assessment questionnaire damage index (HAQ-DI) at each visits (0 week, 12 weeks, and 24 weeks).
3. Pain intensity was assessed by using a standard VAS of 100 mm previously validated to chronic and acute pains.
4. Clinical response to green tea therapy for 24 weeks was calculated from DAS28 scores.
5. human miR-146a and miR-125ba were isolated and subjected to RT-PCR analysis

• Study Type: Observational
• Enrollment (Actual): 150

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

A total of 100 subjects (aged 18-65 years) who were diagnosed as RA with moderate to severe activity at the division of rheumatology and clinical immunology at Mansoura University, between 20 January/2015 and 20 September 2015 were recruited in this prospective study. According to the diagnostic criteria of the American College of Rheumatology (Arnett et al., 1988), all patients classified as showing established RA for more than 8 years.

Description

Inclusion Criteria:

• subjects (aged 18-65 years) who were diagnosed as RA with moderate to severe activity at the division of rheumatology and clinical immunology at Mansoura University, between 20 January/2015 and 20 September 2015 were recruited in this prospective study.
• According to the diagnostic criteria of the American College of Rheumatology (Arnett et al., 1988), all patients classified as showing established RA for more than 8 years.
• Only patients who had higher scores of DAS28-ESR, RA biomarkers, and established radiographic analysis, and were diagnosed with RA according to the 2010ACR/ EULAR classification criteria were included in this study.

Exclusion Criteria:

• Patients who received non-steroidal anti-inflammatory drugs, oral glucocorticoids, had a history of severe deformation of joint, pregnant or lactating women were excluded from this study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Green tea group; A total of 100 subjects (aged 18-65 years) who were diagnosed as RA with moderate to severe activity at the division of rheumatology and clinical immunology at Mansoura University,After starting green tea supplement (4 to 6 cups/day; 60 to 125 mg catechins), patients were evaluated for therapeutic response at baseline and 12, and 24 weeks.	Dietary supplement: Green tea group
control group; fifty healthy normal subjects were included in this study as controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional status	It will be assessed using disease activity score -28 (DAS28) and pre-validated health assessment questionnaire damage index (HAQ-DI). For DAS28 score, the number of swelling joints count (SJC) (0-28) and tender joints count (TJC) (0-28) in all patients were examined and DAS28 scores were calculated . DAS28 values > 2.6 and ≤ 3.2 was considered as low RA disease activity, values > 3.2 and ≤ 5.1 was considered as moderate disease activity and those > 5.1 was considered as high disease activity. In case of HAQ-DI, score calculation involves answering of eight domains(dressing, rising, eating, walking, hygiene, grip, reach and usual activities) with four point likert scale . SDAI values > 3.3 and ≤11 was considered as low RA disease activity, values > 11 and ≤ 26 was considered as moderate disease activity and those > 26 was considered as high disease activity	change from baseline functional status at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity	It will be assessed using the visual analogue scale (VAS). The patients were asked to mark on the VAS scale of 0-10 cm according to their global assessment of pain. The physician marked on the VAS of 0-10 cm according to the physician global assessment. Patients with higher VAS scores were considered with greater pain intensity.	change from baseline functional status at 24 weeks
Abnormal cell physiology and the parthenogenesis of Rheumatoid arthritis (RA)	it will be assessed by estimating the role of micro ribonucleic acid (microRNAs) in maintaining immune and inflammatory responses. In this part, the expression of miRNAs was estimated by real-time polymerase chain reaction (RT-PCR) analysis, whereas serum samples of each patients were subjected to PCR analysis. Patients with higher miRNAs expressionshowed greater abnormal in cell physiology and the pathogenesis of RH. Whereas normal subjects (≤ 1.2), and abnormal subjects ( ˃ 1.2)	change from baseline functional status at 24 weeks

Collaborators and Investigators

• Sponsor: King Saud University

Publications and helpful links

General Publications

• Al-Rawaf HA, Alghadir AH, Gabr SA. MicroRNAs as Biomarkers of Pain Intensity in Patients With Chronic Fatigue Syndrome. Pain Pract. 2019 Nov;19(8):848-860. doi: 10.1111/papr.12817. Epub 2019 Aug 30.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2015
• Primary Completion (Actual): January 20, 2015
• Study Completion (Actual): September 20, 2015

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (Actual): October 25, 2018

Study Record Updates

• Last Update Posted (Actual): October 26, 2018
• Last Update Submitted That Met QC Criteria: October 24, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: RRC-2015-058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: After starting green tea supplement (4 to 6 cups/day; 60 to 125 mg catechins), patients were evaluated for therapeutic response at baseline and 12, and 24 weeks. All patients with RA were subjected for estimation of ESR, CRP, disease activity score in 28 joints (DAS28), patient's global assessment (PGA), and health assessment questionnaire damage index (HAQ-DI) at each visits (0 week, 12 weeks, and 24 weeks). Pain intensity was assessed by using a standard VAS of 100 mm previously validated to chronic and acute pains (Aicher et al., 2012; Szyfelbein et al., 1985). Clinical response to green tea therapy for 24 weeks was calculated from DAS28 scores. Whereas , a decrease of 1.2 points or above in DAS28 scores at 24 weeks of treatment compared with baseline was defined as clinical response according to the EULAR response criteria (van Gestel et al.,1996).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No