Nimsai Herbal for Grade 2-3 Hemorrhoids: A Quadruple-Blind Placebo-Controlled Mechanistic Trial

Overview

This randomized, quadruple-blind, placebo-controlled clinical trial evaluates the efficacy and safety of Nimsai Herbal, a proprietary oral phytotherapeutic formulation, in 50 participants aged 18-70 years with endoscopically confirmed Grade 2-3 internal hemorrhoids. Participants will be randomly assigned in a 1:1 ratio to receive either Nimsai Herbal (600 mg) or identical placebo once daily for 10 consecutive days. The primary endpoint is hemorrhoid regression at Day 10, defined as either a reduction in Goligher grade or a ≥75% reduction in composite hemorrhoid severity score. Secondary endpoints include change in symptom severity measured by Visual Analog Scale and complete symptom resolution rate. The study is designed as a mechanistic signal-detection investigation based on the War-Drill Model, which posits venous congestion as the primary initiating event in hemorrhoid pathogenesis.

This is a prospective, single-center, quadruple-blind, placebo-controlled, parallel-group randomized controlled trial designed as a mechanistic signal-detection study. The trial evaluates the War-Drill Model of hemorrhoid pathogenesis, which proposes that venous congestion, rather than primary vascular deformation, constitutes the indispensable initiating event in hemorrhoid formation. The model distinguishes two hemodynamic phenotypes: War Mode, associated with systemic inflammation and sustained venous congestion, and Drill Mode, characterized by hormonally mediated transient venous engorgement. A total of 50 participants with endoscopically confirmed Grade 2-3 internal hemorrhoids and symptom duration exceeding 6 weeks will be randomized 1:1 to Nimsai Herbal (600 mg once daily) or matching placebo for 10 consecutive days. The study employs quadruple blinding, with participants, care providers, investigators, and outcomes assessors all masked to treatment assignment. An independent Data Safety Monitoring Board will provide ongoing safety oversight. The primary outcome is hemorrhoid regression rate at Day 10, defined as either reduction in Goligher grade or ≥75% reduction in composite severity score. Secondary outcomes include mean change in self-reported symptom severity (VAS) and complete symptom resolution rate. Safety outcomes include incidence of mild gastrointestinal discomfort, serious adverse events, and withdrawals due to adverse events. Diabetic participants will be specifically monitored for transient diarrhea during Days 1-3. The Parola Phenomenon, a patient-reported clinical indicator, will be assessed at baseline to stratify participants into War Mode and Drill Mode phenotypes for exploratory subgroup analyses. The trial is prospectively registered on ClinicalTrials.gov and approved by the Nimsai Academia Ethics Committee. Written informed consent will be obtained from all participants. The complete study protocol, statistical analysis plan, and de-identified individual participant data will be made publicly available through the Dryad Digital Repository.