Assessment of the Effects of Tongjiang Granule in Treating Nonerosive Reflux Disease Overlapping Epigastric Pain Syndrome: Study protocol for a multicenter, double-blind, randomized controlled trial

Abstract

Abstract Background Practice has shown good efficacy in treating overlapping nonerosive reflux disease (NERD) and epigastric pain syndrome (EPS) symptoms through the use of methods for dispersing the liver and draining heat, harmonizing the stomach and lowering rebelliousness, however, there is a lack of high-level clinical evidence. We intend to evaluate the efficacy and safety of a representative formula of this approach, Tongjiang Granule (TJG), in patients with NERD and EPS symptoms overlapping with liver-stomach disharmony syndrome or liver-stomach depression-heat syndrome (NE-LSDS/LSDHS) in a multicenter clinical randomized controlled trial. Methods/design: This study is designed as a prospective, randomized, double-blind, placebo-controlled clinical trial in which 228 subjects with NE-LSDS/LSDHS will be recruited from 4 research centers. All subjects will be randomized into two groups after signing the informed consent form, the experimental group will be treated with TJG and the control group will be treated with the placebo to mimic TJG (l sachet/dose, 3 times/day, orally, 4 weeks). Visits is scheduled at 6 time points, 2 weeks before dosing and weeks 2, 4, 6, 8, and 10 after dosing. The primary outcome indicator will be the primary symptoms VAS score, the secondary outcome indicators will be the score of atypical and other symptoms, score of traditional Chinese medicine syndrome, visceral sensitivity index scale, patient-reported outcome scale, 36-item short-form scale, and hospital anxiety and depression scale. The safety indicators will include pre- and postdose blood, urine routine, stool routine with occult blood, liver and renal function, electrocardiogram, 24-hour esophageal pH impedance (1/3 of subjects), predose urine pregnancy test, and gastroscopy. Adverse events will also be promptly recorded. Discussion This study will evaluate the efficacy and safety of TJG for the treatment of patients with NE-LSDS/LSDHS, and the results will provide high-level clinical research-based evidence for the application of TJG NE-LSDS/LSDHS. Trial registration: ClinicalTrial.gov NCT05312463. Registered on 3 March 2022. All items from the World Health Organization Trial Registration Data Set can be found at https://classic.clinicaltrials.gov/ct2/show/NCT05312463.