Efficacy and Safety of the Chinese Herbal Formula Hewei Jiangni Recipe for NERD With Cold-heat Complex Syndrome: Study Protocol for a Double-blinded Randomized Controlled Trial

Abstract Background Proton pump inhibitor (PPI) is effective for the treatment of non-erosive gastroesophageal reflux (NERD ), but long-term use of PPI is prone to have complications and recurrence after withdrawal. Traditional Chinese medicine (TCM) can relieve the symptoms of reflux and improve the quality of life. The purpose of this study is to evaluate the safety and efficacy of Hewei Jiangni recipe (HWJNR) in the treatment of NERD with cold-heat complex syndrome, clarify the mechanism of HWJNR on NERD based on the correlation analysis of intestinal flora and metabolites. Methods This is a single-center, randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with NERD and TCM syndrome of intermingled heat and cold will be randomly allocated in the ratio of 1:1 to two groups: TCM group and western medicine group. The TCM group will receive HWJNR with Omeprazole Enteric-coated Tablets simulator, while the western medicine group will receive Omeprazole Enteric-coated Tablets with HWJNR simulator. Each group will be treated for 8 weeks. The primary outcome is the score of gastroesophageal reflux disease (GERD) health related quality of life questionnaire (GERD-Q). Secondary outcomes include SF-36 quality of Life scale, patient reported outcomes (PRO) self-rating scale score, syndrome score of TCM, and adverse events. Mechanistic outcome is the correlation analysis of intestinal flora and metabolites from healthy individuals and NERD participants before and after the treatment respectively. Discussion The goal of this trial is to investigate the efficacy and safety of HWJNR in the treatment of NERD with cold-heat complex syndrome, and to study the composition structure and metabolite expression profile of intestinal flora in patients with NERD through 16SrRNA sequencing and metabonomic correlation analysis of fecal flora, which makes us identify the dominant links of treatment and reveal the potential mechanism of HWJNR.ChiCTR2000041225. Registered on 22 December 2020http://www.chictr.org.cn/showproj.aspx?proj=66217