Study of the Effectiveness and Safety of a Herbal Formulation Containing Trachyspermum ammi and Mentha spp. as an Adjunct to Pantoprazole, Compared with Placebo Plus Pantoprazole, on Gastric Ulcer Healing in Patients with Gastric Ulcer

Evaluation of the Efficacy and Safety of a Herbal Product Containing Trachyspermum ammi and Mentha as an Adjunctive Therapy to Pantoprazole, Compared with Placebo Plus Pantoprazole, in the Healing of Gastric Ulcers in Patients with Gastric Ulcer Disease

This is a randomized, triple-blind, placebo-controlled, parallel-group Phase II trial. A total of 134 eligible patients will be allocated by block randomization to intervention and control groups (67 per group).

This clinical trial will be conducted at Loghman Hakim Hospital and, if needed, Modarres Hospital. Eligible patients will be randomized by block randomization into intervention and control groups after informed consent. The study will be triple-blind; participants, investigators, and outcome assessors will be blinded to allocation, with KDS syrup/placebo administered alongside pantoprazole and ulcer healing assessed by endoscopy after 3 months

Inclusion criteria: Patients aged 16–75 years with Helicobacter pylori-negative gastric ulcer. Exclusion criteria: Pregnancy, breastfeeding, recent use of bismuth-containing drugs or antibiotics (within 2 weeks), GI bleeding requiring invasive intervention, gastric ulcer complications, ethanol consumption/substance abuse, and suspected gastric cancer.

Intervention: Pantoprazole 40 mg daily plus KDS syrup 10 mL three times daily for 1 month. Control: Pantoprazole 40 mg daily plus placebo syrup 10 mL three times daily for 1 month.

The primary outcome variable is complete gastric ulcer healing at 3 months after treatment initiation.

Participants will be randomly allocated to either the intervention or control group using block randomization. They will receive one of the following treatment regimens: • Control group: Pantoprazole 40 mg once daily plus placebo syrup, 10 mL three times daily for one month. • Intervention group: Pantoprazole 40 mg once daily plus KDS syrup, 10 mL three times daily for one month. Three months after the initial endoscopy, a follow-up endoscopy will be performed by the same gastroenterologist to reassess ulcer healing. Ulcer stage will be evaluated using the Sakita–Miwa Classification: • Active stage (A): A1 (fresh ulcer with inflamed and edematous margins) and A2 (reduced marginal inflammation). • Healing stage (H): H1 (initial epithelialization from the ulcer margin) and H2 (reduction in ulcer size with convergence of mucosal folds). • Scar stage (S): S1 (red scar, indicating complete healing with residual redness) and S2 (white scar, indicating complete healing with normal mucosal color). Complete healing will be defined as progression to S1 or S2, or complete disappearance of the ulcer. Treatment compliance and adverse events will be assessed by telephone at 2 weeks and 1 month after initiation of treatment. Statistical analysis will be performed using SPSS version 16. Data will be analyzed using the independent t-test and chi-square test, and a p-value < 0.05 will be considered statistically significant.

This study will be conducted as a randomized, triple-blind clinical trial. The participants, investigators, and data analyst will be blinded to treatment allocation. The herbal formulation and placebo will be identical in appearance, color, odor, volume, packaging, and labeling, and will be identified only by unique codes. The randomization codes will be securely maintained by an independent person and will not be disclosed until completion of data analysis, except in the event of a medical emergency requiring unblinding .