. 2020 Sep 16;21(1):795.

doi: 10.1186/s13063-020-04687-3.

Can low-dose methotrexate reduce effusion-synovitis and symptoms in patients with mid- to late-stage knee osteoarthritis? Study protocol for a randomised, double-blind, and placebo-controlled trial

Zhaohua Zhu^{1

2

3}, Qinghong Yu², Xiaomei Leng⁴, Weiyu Han¹, Zhanguo Li⁵, Cibo Huang⁶, Jieruo Gu⁷, Yi Zhao⁸, Kang Wang⁹, Tianwang Li¹⁰, Yifang Mei¹¹, Jianhua Xu⁹, Zhiyi Zhang¹¹, David Hunter^{1

12}, Flavia Cicuttini¹³, Xiaofeng Zeng⁴, Changhai Ding^{14

15

16

17}

Affiliations

¹ Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
² Department of Rheumatology and Clinical Immunology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
³ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
⁴ Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁵ Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, China.
⁶ Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Beijing, China.
⁷ Department of Rheumatology, 3rd Affiliated Hospital of Sun Yet-Sen University Guangzhou, Guangzhou, Guangdong, China.
⁸ Department of Rheumatology & Allergy, Xuanwu Hospital, Capital Medical University, Beijing, China.
⁹ Department of Rheumatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
¹⁰ Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, China.
¹¹ Department of Rheumatology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
¹² Department of Rheumatology, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, Australia.
¹³ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
¹⁴ Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Changhai.Ding@utas.edu.au.
¹⁵ Department of Rheumatology and Clinical Immunology, Zhujiang Hospital of Southern Medical University, Guangzhou, China. Changhai.Ding@utas.edu.au.
¹⁶ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. Changhai.Ding@utas.edu.au.
¹⁷ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. Changhai.Ding@utas.edu.au.

PMID: 32938470
PMCID: PMC7493135
DOI: 10.1186/s13063-020-04687-3

Can low-dose methotrexate reduce effusion-synovitis and symptoms in patients with mid- to late-stage knee osteoarthritis? Study protocol for a randomised, double-blind, and placebo-controlled trial

Zhaohua Zhu et al. Trials. 2020.

. 2020 Sep 16;21(1):795.

doi: 10.1186/s13063-020-04687-3.

Authors

Affiliations

¹ Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
² Department of Rheumatology and Clinical Immunology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
³ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
⁴ Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁵ Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, China.
⁶ Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Beijing, China.
⁷ Department of Rheumatology, 3rd Affiliated Hospital of Sun Yet-Sen University Guangzhou, Guangzhou, Guangdong, China.
⁸ Department of Rheumatology & Allergy, Xuanwu Hospital, Capital Medical University, Beijing, China.
⁹ Department of Rheumatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
¹⁰ Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, China.
¹¹ Department of Rheumatology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
¹² Department of Rheumatology, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, Australia.
¹³ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
¹⁴ Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Changhai.Ding@utas.edu.au.
¹⁵ Department of Rheumatology and Clinical Immunology, Zhujiang Hospital of Southern Medical University, Guangzhou, China. Changhai.Ding@utas.edu.au.
¹⁶ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. Changhai.Ding@utas.edu.au.
¹⁷ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. Changhai.Ding@utas.edu.au.

PMID: 32938470
PMCID: PMC7493135
DOI: 10.1186/s13063-020-04687-3

Abstract

Background: Osteoarthritis (OA) is a common chronic disease in older adults. Currently, there are no effective therapies to reduce disease severity and progression of knee OA (KOA), particularly in mid- to late-stages. This study aims to examine the effect of methotrexate (MTX) on knee effusion-synovitis and pain in symptomatic patients with mid- to late-stage KOA.

Methods/design: This protocol describes a multicentre randomised placebo-controlled clinical trial aiming to recruit 200 participants with mid- to late-stage symptomatic KOA and with effusion-synovitis grade of ≥ 2. Participants will be randomly allocated to the MTX group (start from 5 mg per week for the first 2 weeks and increase to 10 mg per week for the second 2 weeks and 15 mg per week for the remaining period if tolerated) or the placebo group. Primary outcomes are effusion-synovitis size measured by magnetic resonance imaging (MRI) and knee pain assessed by visual analogue scale (VAS). Secondary outcomes are signal intensity alteration within infrapatellar fat pad (IPFP) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and subscores, and the Outcome Measures in Rheumatology Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) responders. Both intention-to-treat and per-protocol analyses will be performed.

Discussion: If MTX intervention can relieve symptoms and reduce inflammation in patients with mid- to late-stage KOA, it has the potential for significant clinical and public health impact as this low-cost and commonly used intervention would delay the time to knee replacement, leading to substantial cost savings and improve quality of life.

Trial registration: ClinicalTrials.gov NCT03815448 . Registered on 21 January 2019.

Keywords: Effusion-synovitis; Methotrexate; Osteoarthritis; Pain.

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Conflict of interest statement

The authors declare that they have no conflict of interests.

Figures

**Fig. 1**
Flow chart of trial participation

See this image and copyright information in PMC

References

1. Felson DT. Clinical practice. Osteoarthritis of the knee. N Engl J Med. 2006;354:841–848. - PubMed
1. Tang X, Wang S, Zhan S, Niu J, Tao K, Zhang Y, Lin J. The prevalence of symptomatic knee osteoarthritis in China: results from the China health and retirement longitudinal study. Arthritis Rheumatol. 2016;68:648–653. - PubMed
1. Huang SL, He XJ, Wang KZ. Joint replacement in China: progress and challenges. Rheumatology (Oxford) 2012;51:1525–1526. - PubMed
1. Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018;52:167–175. - PubMed
1. Conaghan PG, Porcheret M, Kingsbury SR, Gammon A, Soni A, Hurley M, Rayman MP, Barlow J, Hull RG, Cumming J, et al. Impact and therapy of osteoarthritis: the Arthritis Care OA Nation 2012 survey. Clin Rheumatol. 2015;34:1581–1588. - PubMed

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LC2019ZD015/Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education

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Can low-dose methotrexate reduce effusion-synovitis and symptoms in patients with mid- to late-stage knee osteoarthritis? Study protocol for a randomised, double-blind, and placebo-controlled trial

Affiliations

Can low-dose methotrexate reduce effusion-synovitis and symptoms in patients with mid- to late-stage knee osteoarthritis? Study protocol for a randomised, double-blind, and placebo-controlled trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical