Role of Statin on the Gastric Inflammation in Patients at High Risk of Gastric Cancer

Statins are commonly used as cholesterol-lowering medications and have shown effectiveness in the primary and secondary prevention of heart attack and stroke. In addition, several recent studies of human cancer cell lines and animal tumor models indicate that statins may have chemopreventive properties through the arresting of cell-cycle progression. The chemopreventive effect of statins was demonstrated in some kind of human tumors including colorectal cancer. In addition, recent one large epidemiologic study showed that statins decreased risk of gastric cancer. On the other hands, it has been well known that Helicobacter pylori infection induces gastric atrophy and intestinal metaplasia, which are premalignant lesions of gastric cancer. Progression of these premalignant lesions could be limited by H. pylori eradication. In addition, a recent double blind randomization study revealed that simvastatin as adjuvant to standard therapy improves significantly the H. pylori eradication rate. Therefore, investigators conjecture that statins may have an adjuvant role for inhibition of gastric carcinogenesis. investigators aim to evaluate the role of statins in gastric carcinogenesis by observing the changes of gastric inflammation under statins.

Study Overview

• Status: Completed
• Conditions: Early Gastric Cancer or Gastric Adenoma
• Intervention / Treatment: Drug: Arm2: Placebo; Drug: Arm1: Statin

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age, between 20 and 70
2. Early gastric cancer or adenoma which is achieved curative resection by endoscopic submucosal dissection
3. ECOG performance status 0 or 1

Exclusion Criteria:

1. Previous subtotal gastrectomy or gastrostomy
2. Repeated endoscopic submucosal dissection
3. Two or more synchronous lesions
4. Presence of gastric or duodenal ulcer except artificial ulcer due to endoscopic submucosal dissection
5. History of drugs which are able to induce gastric ulcer including aspirin, NSAIDs, and steroid (30 days or more, within 1 year at the time of screening
6. Indication of statins, including dyslipidemia, myocardial infarction, and heart failure.
7. Develop of complications caused by endoscopic submucosal dissection, including bleeding, perforation, and pneumonia
8. LDL < 70 mg/dL
9. Allergy to statins
10. Pregnancy or breast milk feeding
11. Active infection
12. Significant cardiopulmonary disease
13. Active hepatitis or severe hepatic dysfunction
14. Severe renal dysfunction
15. Severe bone marrow dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; Without simvastatin	Drug: Arm2: Placebo; Study1 (only H. pylori infected patients) Arm2: All patients undergo H. pylori eradication therapy after 2 weeks from the endoscopic submucosal dissection. In this arm2, all patients take placebos for 6 months. Then, follow-up endoscopy for gastric biopsy and CLO test will be performed after 6.5 months from the endoscopic submucosal dissection. Study2 (only H. pylori non-infected patients) Arm2: In this arm2, all patients start taking placebos after 2 weeks from the endoscopic submucosal dissection. Follow-up endoscopy for gastric biopsy will be performed after 6.5 months from the endoscopic submucosal dissection.; Other Names: C10AA-Hmg coa reductase inhibitors
Experimental: Statin group; With simvastatin	Drug: Arm1: Statin; Study1 (only H. pylori infected patients) Arm1: All patients undergo H. pylori eradication therapy after 2 weeks from the endoscopic submucosal dissection. In this arm2, all patients take statins for 6 months. Then, follow-up endoscopy for gastric biopsy and CLO test will be performed after 6.5 months from the endoscopic submucosal dissection. Study2 (only H. pylori non-infected patients) Arm1: In this arm2, all patients start taking statins after 2 weeks from the endoscopic submucosal dissection. Follow-up endoscopy for gastric biopsy will be performed after 6.5 months from the endoscopic submucosal dissection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of the patients with high-risk (III/IV) OLGA stages	patients with high-risk OLGA stages will be assessed by histologic examinations	6 months from the start of taking the statins

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): June 19, 2018
• Study Completion (Actual): June 19, 2018

Study Registration Dates

• First Submitted: March 7, 2013
• First Submitted That Met QC Criteria: March 14, 2013
• First Posted (Estimate): March 19, 2013

Study Record Updates

• Last Update Posted (Actual): March 29, 2019
• Last Update Submitted That Met QC Criteria: March 27, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Statin; Gastric inflammation; Gastric cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Adenoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Other Study ID Numbers: 4-2012-0889