Congrong Runtong oral liquid for functional constipation: A multicenter, placebo-controlled phase II trial

BACKGROUND: This study aimed to evaluate the efficacy and safety of Congrong Runtong Oral Liquid (CROL) in treating functional constipation of Yang-deficiency type in adults. OBJECTIVE: To determine the efficacy of Congrong Runtong Oral Liquid (CROL) versus placebo in adults with functional constipation of Yang-deficiency type. METHODS: In this multicenter, double-blind, placebo-controlled randomized clinical trial, 180 participants aged 18-70 years, diagnosed with functional constipation meeting the Rome IV and Yang-deficiency type TCM criteria, were randomized 1:1:1 to receive CROL (3 g or 6g/day) or placebo for 8 weeks. The primary outcome was treatment response (≥ 3 complete spontaneous bowel movements [CSBMs] per week plus increase of ≥ 1 CSBMs per week from baseline for ≥ 4 weeks during the 8-week treatment period). Secondary outcomes included CSBMs, spontaneous bowel movements [SBMs], fecal characteristics, stool passage difficulty, PAC-QOL scores, rescue medication use and adverse events. Outcomes were assessed over 8 weeks. RESULTS: Among participants (mean age 44.5 years; 80% female), the response rate was 60.7% (37/61) with 6g/d CROL, 35.0% (21/60) with 3g/d CROL, and 18.6% (11/59) with placebo (p < 0.0001 for 6g/d vs placebo; p = 0.044 for 3g/d vs placebo). Weekly CSBMs were 2.0 (1.3) (6g/d), 1.5 (1.4) (3g/d), and 1.2 (1.2) (placebo) (p = 0.001 for 6g/d vs placebo). There was no statistically significant difference in weekly SBMs among the three groups, although the 6g/d CROL group showed a numerical trend toward higher SBMs (3.7 [1.9]) compared with the placebo group (3.1 [1.8], p = 0.0735). The rate of treatment-related AEs was 1.6% in the 6g/day group, 0.0% in the 3g/day group, and 3.4% in the placebo group, respectively (p = 0.3241). No severe events were reported. CONCLUSION: CROL was effective and well-tolerated in adult patients with functional constipation of the Yang-deficiency type. REGISTRATION NUMBER: NCT05803161.