YQD Combined With Plant Lactobacillus for Slow Transit Constipation

This is a single-center, prospective, assessor-blinded, parallel-group, superiority randomized controlled trial with a 1:1:1:1 allocation ratio. The study is conducted at the Department of Colorectal Surgery, The First People's Hospital of Lin'an District, Hangzhou, China.

Study Population: Adult patients (aged 18-75 years) diagnosed with slow transit constipation (STC) according to Rome IV criteria, with delayed colonic transit confirmed by a colon transit study (retention of ≥20% of markers at 72 hours). Key exclusion criteria include outlet obstruction constipation, secondary constipation due to organic diseases, history of abdominal surgery (except appendectomy or cholecystectomy), severe systemic illness, pregnancy or lactation, known allergy to any herbal ingredient or Lactobacillus preparation, and use of medications affecting gastrointestinal motility within 4 weeks before screening.

Interventions: All four groups receive a background therapy of mosapride citrate 5 mg three times daily for 8 weeks. On top of that: (1) Group A receives YQD (one dose daily) + plant-derived Lactobacillus (compound Lactobacillus tablets, 3 tablets twice daily); (2) Group B receives YQD + placebo for Lactobacillus; (3) Group C receives Lactobacillus + placebo for YQD; (4) Group D receives placebo for both YQD and Lactobacillus. The herbal decoction consists of 12 herbs: Cistanche deserticola (Roucongrong) 15 g, Atractylodes macrocephala (Baizhu) 15 g, Astragalus membranaceus (Huangqi) 20 g, Cynanchum wilfordii (Geshangiao) 15 g, Scrophularia ningpoensis (Xuanshen) 12 g, Raphanus sativus (Laifuzi) 15 g, Dioscorea opposita (Shanyao) 12 g, Galli Gigerii Endothelium Corneum (Jineijin) 15 g, Sesamum indicum (Heizhima) powder 12 g, Cyathula officinalis (Chuanniuxi) 15 g, Massa Medicata Fermentata (Shenqu) 15 g, and Colla Corii Asini (Ejiao) 12 g. One dose is decocted and concentrated to 100 mL, taken once daily in the morning.

Outcome Measures: The primary outcome is the change from baseline to week 8 in the Constipation Severity Score (CSS), which evaluates stool frequency, consistency, straining, abdominal pain, and use of aids. Secondary outcomes include: (1) change in Patient Assessment of Constipation Quality of Life (PAC-QOL) scores; (2) colonic transit measured by percentage of retained markers at 72 hours; (3) gut microbiota quantification via 16S rRNA PCR for Escherichia coli, Lactobacillus, and Bifidobacterium; (4) relapse rate during 6-month follow-up (assessed at 1, 3, and 6 months post-treatment); and (5) adverse events graded per CTCAE v5.0.

Sample Size: Based on pilot data, the mean CSS reduction in the triple-combination group is expected to be 6.0 (SD 3.5), versus 3.5 (SD 3.0) in the mosapride-alone group. To detect a difference of 2.5 points with 80% power and a two-sided alpha of 0.05, accounting for a 20% dropout rate, 30 patients per group (total 120) are required.

Statistical Analysis: Primary analysis will be on an intention-to-treat (ITT) basis; per-protocol analysis will be sensitivity. Baseline characteristics will be compared using ANOVA or chi-square tests. The primary outcome (change in CSS) will be analyzed by ANCOVA with baseline CSS as covariate and treatment group as fixed factor, followed by post-hoc pairwise comparisons with Bonferroni correction. Secondary continuous outcomes will be analyzed similarly. Relapse rates will be compared using chi-square tests. Repeated measures will use mixed-effects models. Missing data will be handled by multiple imputation. Two-sided p < 0.05 will be considered statistically significant.

Ethics and Dissemination: The protocol has been approved by the Medical Ethics Committee of The First People's Hospital of Lin'an District, Hangzhou (approval number: LAYY-EC-2024-037). Written informed consent will be obtained from all participants. Results will be submitted for publication in a peer-reviewed journal and presented at national and international conferences.