Efficacy and safety of modified Gwakjeongtang (herbal medicine) for diarrhea-predominant irritable bowel syndrome: A randomized, double-blind, placebo-controlled trial

BACKGROUND: Irritable bowel syndrome (IBS) significantly impairs quality of life, and current treatments often provide insufficient symptom relief. Gwakjeongtang is the most frequently prescribed herbal medicine for IBS patients in Korea. We aimed to explore the efficacy and safety of modified Gwakjeongtang (mGJT) compared with placebo in patients with diarrhea‐predominant IBS (IBS‐D). METHODS: This pilot double‐blind, placebo‐controlled, parallel‐group randomized clinical trial was conducted at a single academic medical center from September 2023 to January 2025. Adults with IBS‐D meeting Rome IV criteria were enrolled. Of 63 participants screened, 60 were randomized 1:1 to receive mGJT granules (10 g) or placebo administered orally three times daily for 4 weeks. The primary outcome was overall response rate, defined as achieving daily response criteria (≥30% reduction in worst daily abdominal pain intensity from baseline and Bristol Stool Scale ≤5 for all bowel movements) on ≥50% of treatment days over 4 weeks. RESULTS: Among 60 randomized participants (16 male; mean age 46.0 years), 59 (98.3%) completed primary outcome assessment. The overall response rate was significantly higher with mGJT than placebo (55.2% vs. 26.7%; odds ratio 3.4; 95% confidence interval 1.1‐10.1; P=.03). Sensitivity analysis assuming the missing participant was a nonresponder showed consistent results (53.3% vs. 26.7%; odds ratio 3.1; 95% confidence interval 1.1‐9.3; P=.04). No intervention‐related adverse events occurred. CONCLUSION: These pilot findings suggest mGJT may benefit patients with IBS‐D. Confirmation in a larger definitive trial is warranted given the pilot study limitations and small sample size. TRIAL REGISTRATION: Clinical Research Information Service of Korea (KCT0008523).