Observation of The Curative Effect of Guizhi-Shaoyao-Zhimu Decoction Combined With Methotrexate In The Treatment of Early Rheumatoid Arthritis Based On Ultrasonic Evaluation: Study Protocol of A Randomized, Double-Blind, Controlled Clinical Trial

Abstract

Background: Rheumatoid arthritis(RA) is a chronic inflammatory autoimmune disease with the primary clinical symptoms of joint swelling and pain. Early detection of erosion and synovial inflammation at an active stage resulting from RA can prevent damage to the joints and activity restriction. However ,there are still many patients who do not respond to these treatments, the development of newer, safer drugs is urgently needed. Compared to Western medicine, Guizhi-Shaoyao-Zhimu decoction has equal or higher efficacy and safety for RA patients. With the widespread use of musculoskeletal ultrasound (MSUS), this technology holds great value for the degree of joint damage in RA patients, guiding the clinical selection of treatments, and assessing of prognosis. Therefore, we designed a double blinded randomized controlled clinical trial to measure the safety and efficacy of Guizhi-Shaoyao-Zhimu decoction in treating early stage RA using MSUS. Methods: This study is a randomized, double-blinded, parallel group, placebo-controlled trial. A total of 152 adult participants with early RA will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be Guizhi-Shaoyao-Zhimu decoction plus the conventional medicine methotrexate and the control intervention will be placebo plus the conventional drug methotrexate for 3 months. In addition, both groups will receive folic acid during treatment to prevent side effects from methotrexate. The primary outcomes are the erythrocyte sedimentation rate (ESR),C-reactive protein(CRP), hepatic and renal function , visual analog scale, disease activity Score in 28 joints, measurement scale for TCM symptoms, and 7-joints ultrasound score. Discussion: We designed this double blinded randomized controlled clinical trial to evaluate the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in RA patients using MSUS. The results of this trial may provide insights into how to improve the clinical symptoms, of RA patients and delay further joint destruction. We hope that this trial may provide preliminary evidence of the efficacy of Guizhi-Shaoyao-Zhimu decoction in treating RA patients and that these results aid researchers, practitioners and patients alike. Trial registration: Chinese Clinical Trials Register, ChiCTR2000036141. Registered on 21 August 2020 (Retroactively registered).

A study of the molecular mechanism of action of Jiawei Guizhishaoyaozhimu Decoction during rheumatoid arthritis therapy based on basic of network pharmacology and experimental verification

“…Previous research has reported that GSZD can reduce the levels of pro-inflammatory factors TNF-α, IL-1β, IL-17 and receptor activator for NF-κB ligand (RANKL), thus inhibiting the recruitment and differentiation of osteoclast precursors. GSZD may also increase the secretion of osteoclastogenesis inhibitory factor (OPG), thereby regulating the ratio of RANKL/OPG that could promote the protection of bone to improve the injury of cartilage and synovium in CIA rats ( 51 ). In the present study, ‘Gu Sui Bu’ (Rhizoma Drynariae), ‘Bu Gu Zhi’ (Fructus Psoraleae) and ‘Sang Zhi’ (Ramulus Mori) were added to the original medicinal preparation.…”