Trial Information

Randomized Multi-Intervention Trial to Inhibit Precancerous Gastric Lesions in Lingu, Shandong Province, China

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.