DLBS2411 Treatment for Ulcer Healing in Non-Bleeding Peptic Ulcers

Study Overview
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Brief Summary
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This is a 2-arm, prospective, double-blind, double-dummy, randomized-controlled study using DLBS2411 at a dose of 250 mg twice daily (before morning and evening meals), or omeprazole at a dose of 40 mg once daily (before morning meal), for an 8-week course of therapy, for the treatment of patients with any non-bleeding peptic ulcers. DLBS2411 is a bioactive fraction of an Indonesian native herbal, Cinnamomum burmanii, locally known as kayu manis have been proven at cellular and genetic levels to have an antiulcer effect through both suppressing the gastric acidity and enhancing gastric mucosal protection. The anti-secretory effect of DLBS2411 is exerted through the inhibition of H+/K+ ATPase 'pump' as well as down-regulation of the H+/K+ ATPase gene expression, thus suppressing gastric acid secretion; while its gastro-protective defense mechanism works through the promotion of COX-2 derived prostaglandin (PgE2) synthesis, stimulating gastric-epithelial mucous and bicarbonate secretion; anti-oxidative activity; and endothelial-nitric oxide (NO) formation. Recent study of DLBS2411 in healthy volunteers demonstrated the effective role and safety of DLBS2411 in suppressing intragastric acidity. Having such mechanisms of action, DLBS2411 is hypothesized to benefit in peptic ulcers.

Detailed Description
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A total of 140 subjects will be allocated into 2 groups of treatment; each group will consist of 70 subjects with the treatment regimens: Treatment I : 2 capsules of Omeprazole 20 mg, once daily and 1 placebo caplet of DLBS2411, twice daily Treatment II : 1 caplet of DLBS2411 250 mg, twice daily and 2 placebo capsules of omeprazole, once daily DLBS2411 will be administered twice daily at least 30 minutes before morning and evening meals, while omeprazole, once daily before morning meals, for 8 weeks of study period. The eligible subjects will receive either study medication (Treatment 1 or Treatment 2), for 8 weeks of treatment; and will be instructed to come to the clinic every 4-week interval throughout the study period. Subjects will be evaluated for treatment efficacy at baseline and at interval of 4 weeks over the 8-week course of therapy. The safety profile of study medication other than vital signs and adverse event will be measured at baseline and end of study. Vital signs and adverse event will be measured at baseline and every follow-up visit including end of study.

Official Title
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DLBS2411 Treatment for Ulcer Healing in Non-Bleeding Peptic Ulcers

Conditions
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Non-Bleeding Peptic Ulcers

Intervention / Treatment
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* Drug: Omeprazole
* Drug: Placebo caplet of DLBS2411
* Drug: DLBS2411
* Drug: Placebo capsule of Omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged 18-75 years old. Diagnosed as non-bleeding peptic ulcers who do not require endoscopic therapy, as confirmed by : The presence of endoscopically confirmed gastric or duodenal ulcer(s) at size(s) of at least 3 mm or larger. Subjects with low-risk of recurrent bleeding, defined as both: Complete Rockall score of ≤ 7. Endoscopic stigmata (lesion) of grade II-C or III based on Forrest classification. Able to take oral medication. Exclusion Criteria: For females of childbearing potential: pregnancy, breast-feeding, the intention of becoming pregnant during the study participation. Patients must accept pregnancy tests during the trial if menstrual cycle is missed Fertile patients must use a reliable and effective contraceptive History of or known or suspected Zollinger Ellison syndrome. History of endoscopic therapy for bleeding ulcer within the past 4 weeks. Indication for endoscopic hemostasis therapy. Presence of Helicobacter pylori infection History of or known coronary artery disease (CAD), congestive heart failure, pulmonary disease, and any other uncontrolled chronic diseases. History of or known gastrointestinal malignancy or ulcers associated to malignancy. Currently known being afflicted by serious infection(s). Inadequate liver function Inadequate renal function Subjects being under therapy with any herbal medicines. Known hypersensitivity or idiosyncratic reaction or adverse drug reactions to proton pump inhibitors (PPIs). Participation in any other clinical studies within 30 days prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment I<br>2 Omeprazole capsules 20 mg once daily and 1 placebo caplet of DLBS2411, twice daily | Drug: Omeprazole<br>* 2 Omeprazole capsules 20 mg, once daily<br>Drug: Placebo caplet of DLBS2411<br>* 1 placebo caplet of DLBS2411, twice daily<br>* Other names: Placebo caplet of Redacid;|
| Experimental: Treatment II<br>1 DLBS2411 caplet 250 mg twice daily and 2 placebo capsules of Omeprazole once daily | Drug: DLBS2411<br>* 1 DLBS2411 caplet 250 mg, twice daily<br>* Other names: Redacid;Drug: Placebo capsule of Omeprazole<br>* 2 placebo capsules of Omeprazole, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endoscopic ulcer healing rate | Endoscopic ulcer healing rate after 8 weeks of treatment. Ulcer healing rate is defined as the proportion of subjects with complete ulcer-healing (referring to S1 or S2 Scarring stage according to Sakita-Fukutomi classification) as confirmed by endoscopic finding. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The improvement rate of each of gastric symptoms | The improvement rate of each of gastric symptoms at each of the follow-up visits (after 4 and 8 weeks of treatment): abdominal or epigastric pain (middle or upper stomach) nausea or vomiting, bloating | 4 and 8 weeks | 
| The quality of ulcer healing | The quality of ulcer healing as measured by the levels of gastric mucosal bFGF (basic fibroblast growth factor) and COX-2 (cyclo-oxygenase), at baseline and Week 8 of treatment. | 8 weeks | 
| Mucosal thickness | Gastric mucosal thickness will be measured quantitatively as the expression of MUC5AC by immunohistochemistry (IHC) method, at baseline and Week 8 of treatment. | 8 weeks | 
| Patients' global evaluation for their symptoms | Patients' global evaluation for their symptoms categorized as: no improvement or slightly improved or moderately improved or markedly improved, at Week 4 and 8 (end of study). | 4 and 8 weeks | 
| Liver function | Liver function (serum ALT (alanine-aminotransferase), serum AST (aspartate-aminotransferase), alkaline phosphatase, total bilirubin) at baseline and at the end of study | 8 weeks | 
| Renal function | Renal function (serum creatinine and BUN (blood urea nitrogen) level) at baseline and at the end of study | 8 weeks | 
| Adverse events | Adverse event, will be observed throughout the study conduct | 4 and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Bleeding Peptic Ulcers, DLBS2411, Ulcer Healing