Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01520259 |
| Other study ID # |
999912020 |
| Secondary ID |
12-C-N020 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 10, 2012 |
Study information
| Verified date |
August 8, 2019 |
| Source |
National Institutes of Health Clinical Center (CC) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background:
- Chile has the highest diagnosis and death rates of gallbladder cancer in the world.
Gallbladder cancer is also the leading cause of cancer death in Chilean women. High rates of
gallstones and obesity, as well as genetic concerns, may explain these high rates.
Researchers want to study gallbladder cancer in more depth in Chile. A small study must be
done to see if a full-scale study is feasible.
Objectives:
- To test the methods and procedures of a small-scale study of gallbladder cancer in Chile.
Eligibility:
- Individuals at least 18 years of age who have gallbladder cancer or gallstones, or are
healthy control volunteers.
- Participants will be recruited from four clinical centers in Chile.
Design:
- Participants will be screened with a physical exam and medical history. Because
gallbladder cancer has a high fatality rate, family members may be asked to provide
additional medical history information if study participants die or become too ill to
provide this information.
- Participants will provide blood, urine, stool, hair, fingernail, and saliva samples.
- Gallstones, bile, and tissue samples will be collected from those who have gallbladder
removal surgery. Normal and tumor tissue samples will be collected as needed.
- Treatment will not be provided as part of this protocol. This is a data collection study
only.
Description:
Gallbladder cancer is a leading cause of cancer death among women in Chile, which has among
the highest reported gallbladder cancer incidence and mortality rates in the world.
Gallbladder cancer provides a particularly good model for understanding the role of
inflammation in carcinogenesis since the major risk factor, gallstones, causes substantial
inflammation in the gallbladder. Chile also has a high prevalence of obesity, diabetes, and
metabolic syndrome, which are increasingly understood as inflammatory disorders, but the
extent to which their carcinogenic effects are mediated through inflammatory pathways is
unknown.
While the vast majority of gallbladder cancer cases have gallstones, only a small fraction of
gallstone patients ever develop gallbladder cancer. Since there is no way to identify this
small
proportion at risk, gallstone cases are cholecystectomized, which, given large absolute
numbers of individuals with gallstones, results in overtreatment of some and under-treatment
of others in a high-risk area like Chile. While cholecystectomy is standard treatment for
symptomatic relief, there are more people who need surgery than there are surgeons to perform
them, and individuals aged 34-49 are prioritized for treatment, regardless of symptoms. This
practice may lead to overtreatment among 34-49-year-olds and under treatment of individuals
aged 50 and above since they have to wait longer for surgery. At the same time, about 30% of
patients with a biliary colic attack will never have another attack, and cholecystectomy does
not always lead to the cessation of symptoms. In addition, cholecystectomy has been
associated with an increased risk of other digestive diseases. Thus, cholecystectomy may not
be needed in all gallstone patients and may in fact increase the risk of cancer in some.
Better predictors of risk are clearly needed.
As with other cancers, dysplasia is an important epidemiologic endpoint as the immediate
precursor to cancer since the vast majority of gallbladder cancers develop through a
histologic continuum of chronic cholecystitis, pseudopyloric metaplasia, incomplete
intestinal metaplasia, dysplasia, and cancer. Thus, our aim is to identify risk factors for
gallbladder dysplasia and cancer (GDC) and potential non-invasive risk stratification
methods, such as ultrasound characteristics alone or in combination with inflammatory markers
and patient characteristics, to better understand the etiology and natural history of GDC and
to help inform strategies for GDC prevention.
Together with collaborators at Pontifica Universidad Catolica (PUC), we successfully
completed a pilot study in Chile that was previously reviewed and approved by SAG and
provided baseline data for the proposed study. Our pilot demonstrated high recruitment rates
in the target enrollment area (80%) and high rates of questionnaire completion (100%), blood
collection (78% population-based controls), and participant retention (93% of eligible
completed a follow-up visit). Information from the pilot was used to optimize procedures for
the longitudinal study. We also found that both gallstones and gallbladder cancer were
associated with systemic immune alterations, which as we previously demonstrated, reflect
inflammatory changes in the gallbladder detectable in bile. The next step is to demonstrate
that these markers precedeGDC by longitudinally measuring their levels among gallstone
patients.
We propose to prospectively assess risk factors and early detection markers for GDC by
conducting the Chile Biliary Longitudinal Study (BiLS), a cohort study of 6250 individuals
with gallstones from the high- risk southern-central region of Chile. Because women are twice
as likely to have gallstones and twice as likely to have gallbladder cancer as men, we plan
to maximize our screening efficiency and number of outcomes by screening and enrolling women
only. Since Chile is conducting a general population cohort in a small town in the high-risk
area, will we benefit from the infrastructure that is already in place and be able to compare
the women in our study to a set of men with gallstones enrolled by the Chilean study. We plan
to enroll women with gallstones over 2 years and follow them for 6 years, conducting visits
every other year to collect data on the primary exposures of interest, inflammatory markers
and ultrasound characteristics, as well as additional exposures of interest, such as
infections, genetics, and environmental exposures (e.g., aflatoxin, pesticides). The cohort
will be complemented by an incident case-control study of 300 women with gallbladder cancer
and 600 controls with and without gallstones obtained from the cohort participants.
