A Randomized Multi-Intervention Trial to Inhibit Precancerous Gastric Lesions in Lingu, Shandong Province
Condition: Precancerous Gastric Lesions
Study type: Interventional
Phase: Phase 3

Summary: 
      The Division of Cancer Epidemiology and Genetics is conducting a collaborative randomized
      multi-intervention trial with the Beijing Institute for Cancer Research to evaluate the
      etiologic role of Helicobacter pylori, garlic, and certain micronutrients in the multi-step
      process of gastric carcinogenesis. The primary endpoint will not be cancer, but rather the
      precancerous lesions severe chronic atrophic gastritis, intestinal metaplasia, and dysplasia.
      The study is designed to detect a stabilizing or mild decrease in the expected age-related
      progression of precancerous lesions over the course of the trial. Thus the trial can be
      considered a study of the potential inhibitors of the process of gastric carcinogenesis. The
      trial will also provide an evaluation of therapy for H. pylori, including an assessment of
      reinfection rates, a critical need for formulating strategies for infection control in China
      and other developing countries. Participating in the trial are approximately 3400 adults aged
      35-70 who were part of an ongoing survey of precancerous gastric lesions in 13 Linqu villages
      in Shandong Province. Linqu appears to be an ideal setting for the trial since stomach cancer
      rates are among the highes in the world, precancerous gastric lesions are prevalent, and the
      population is stable and well characterized. These individuals will be randomly assigned
      (taking H. pylori positivity into account) into 8 intervention groups according to a 2(3)
      factorial design. The interventions are: 1) initial treatment of H. pylori infection with
      ameprazole and amoxicillin followed by 2) daily supplementation with a combination of
      alpha-tocopherol, vitamin C, and selenium; and 3) daily supplementation with garlic extracts.
      No serious side effects have been seen from any of the interventions to date. The study staff
      will continue to monitor for possible adverse reactions and the population will receive
      routine medical care follow-up throughout the course of the trial.

      As part of the ongoing study in Linqu, all participants received an endoscopic exam in the
      fall of 1994. Repeat gastroscopic exams with biopsies at 7 standard gastric sites will be
      conducted during March to May, 1999 and March to May, 2003 to detect early cancers and to
      evaluate gasatric mucosal status. The subjects will be categorized according to the most
      advanced lesions detected in all biopsies and assigned a severity score. The three major
      endpoints for analysis will be: 1) prevalence of dysplasia or cancer 2) prevalence of sever
      chronic atrophic gastritis, intestinal metaplasia, dysplasia, or cancer; and 3) average
      severity score.
    

Detailed description: 
      The Division of Cancer Epidemiology and Genetics is conducting an 8-year collaborative
      randomized multi-intervention trial with the Beijing Institute for Cancer Research to
      evaluate the etiologic role of Helicobacter pylori, garlic, and certain micronutrients in the
      multi-step process of gastric carcinogenesis. The primary endpoint will not be cancer, but
      rather the precancerous lesions severe chronic atrophic gastritis, intestinal metaplasia, and
      dysplasia. The study is designed to detect a stabilizing or mild decrease in the expected
      age-related progression of precancerous lesions over the course of the trial. Thus the trial
      can be considered a study of the potential inhibitors of the process of gastric
      carcinogenesis. The trial will also provide an evaluation of therapy for H. pylori, including
      an assessment of reinfection rates, a critical need for formulating strategies for infection
      control in China and other developing countries. Participating in the trial are approximately
      3400 adults aged 35-70 who were part of an ongoing survey of precancerous gastric lesions in
      13 Linqu villages in Shandong Province. Linqu appears to be an ideal setting for the trial
      since stomach cancer rates are among the highest in the world, precancerous gastric lesions
      are prevalent, and the population is stable and well characterized. These individuals will be
      randomly assigned (taking H. pylori positivity into account) into 8 intervention groups
      according to a 2(3) factorial design. The interventions are: 1) initial treatment of H.
      pylori infection with omeprazole and amoxicillin followed by 2) daily supplementation with a
      combination of alpha-tocopherol, vitamin C, and selenium; and 3) daily supplementation with
      garlic extracts. Compliance was excellent and no serious side effects were seen from any of
      the interventions.

      As part of the ongoing study in Linqu, all participants received an endoscopic exam in the
      fall of 1994. Repeat gastroscopic exams with biopsies at 7 standard gastric sites conducted
      during March to May, 1999 and March to April, 2003 to detect early cancers and to evaluate
      gastric mucosal status. The subjects will be categorized according to the most advanced
      lesions detected in all biopsies and assigned a severity score. The three major endpoints for
      analysis will be: 1) prevalence of dysplasia or cancer 2) prevalence of severe chronic
      atrophic gastritis, intestinal metaplasia, dysplasia, or cancer; and 3) average severity
      score.

      The major endpoint paper was published in JNCI in 2006. Additional analyses of the trial data
      are underway. A continuation study is proceeding that will allow for follow-up of the
      approximately 3070 remaining trial participants through 2010 on the long-term effects of the
      previous treatments on gastric cancer incidence and on cause-specific death rates and allow
      approximately 364 participants in the previous study with advanced gastric lesions in 2003 an
      opportunity for annual endoscopic screening for gastric cancer.
    

Intervention name(s): Amoxicillin/omeprazole
Intervention type(s): Drug
Intervention description(s): To treat Helicobacter pylori infections. 2 week course of amoxicillin 1gm bid, omeprazole 20mg bid. This factorial trial also investigated a supplement of vitamin C, vitamin E and selenium and a garlic supplement.
Intervention MeSH terms: Amoxicillin; Omeprazole
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Helicobacter Pylori; Gastric Cancer Prevention; Precancerous Gastric Lesions