Congrong Runtong Oral Liquid for Functional Constipation: A Multicenter, Placebo-controlled Phase II Trial

• Congrong Runtong Oral Liquid can significantly enhance the treatment response rate in adult patients suffering from functional constipation. • In this randomized clinical trial encompassing 180 participants with functional constipation of the Yang - deficiency type, those who were administered Congrong Runtong Oral Liquid demonstrated a significant increase in the treatment response rate when compared to the placebo group. • This trial offers a treatment alternative for patients with functional constipation who do not respond to lifestyle modifications. 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. To determine the efficacy of Congrong Runtong Oral Liquid (CROL) versus placebo in adults with functional constipation of Yang-deficiency type. 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 (3g 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. 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. CROL was effective and well-tolerated in adult patients with functional constipation of the Yang-deficiency type. NCT05803161.