Abstract
BACKGROUND: Irritable bowel syndrome (IBS) is a common gut-brain interaction disorder, prevalent in the general population. Current medication treatments often leave patients undertreated. Therefore, more and more IBS patients are choosing complementary and alternative medicines for treatment, especially Chinese medicine (CM). However, the therapeutic benefits of CM for IBS have not been well-accepted, and some scholars have attributed the effects of CM to a "placebo effect". It is generally recognized that different placebos could lead to different effects, and that the CM placebo effect is especially high. We think CM treatment responses may be obscured by high, non-specific placebo responses in clinical trials, and thus it is difficult to demonstrate successful treatment effects in a research setting. Thus, ascertaining the magnitude of the CM placebo effect will provide valuable support for accurately understanding CM therapeutic benefits. This study aims to evaluate the placebo and nocebo effects of CM (Tiao-Chang Ke-Min granules, TCKM) in diarrhea-predominant IBS (IBS-D) treatment. METHODS: We plan to use a balanced experimental design embedded in a randomized controlled trial to investigate CM placebo and nocebo effects. This design involves two essential factors: participants' expectations regarding their treatment and the treatment that they actually receive. This balanced design enables the researchers to control the factor of participants' treatment expectations. We use a semi-scripted description of group assignment to elicit participants' expectations regarding IBS-D treatment. Eligible participants will be randomized into 4 groups at a ratio of 1:1:1:1, and receive either TCKM granules or placebo granules. The treatment duration will be 4 weeks. The primary outcome is the proportion of IBS Severity Scoring System responders at the end-of-treatment. The secondary outcomes include individual symptoms, adequate relief, quality of life, and anxiety and depression. This trial has been reviewed and approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (BF2021-082-01). DISCUSSION: To our knowledge, this will be the first trial to investigate CM placebo and nocebo effects in the IBS population. Therefore, this trial may have a real impact on clinical studies and routine practice in the relevant fields. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300067549), registered on 11 January 2023.