Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02692911 |
| Other study ID # |
999916070 |
| Secondary ID |
16-C-N070 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 11, 2017 |
| Est. completion date |
June 15, 2020 |
Study information
| Verified date |
June 2020 |
| Source |
National Institutes of Health Clinical Center (CC) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background:
The gallbladder is a small organ below the liver. Gallbladder cancer is a leading cause of
cancer death among women in Chile. Chile also has among the highest rates of gallbladder
cancer and death in the world. Researchers in a high-risk region of Chile want to find out
more about this type of cancer. They especially want to know how inflammation affects the way
it develops.
Objective:
To better understand the causes of gallbladder diseases and factors that may be associated
with them.
Eligibility:
Women ages 50 74 with gallbladder cancer who are covered by the Chilean national health
system.
Other people over age 21 with gallbladder disease.
Healthy adults over age 21.
Design:
Participants may be screened with an ultrasound. They may be asked questions about their
health.
Participants will have an ultrasound of the abdomen. This can be done at the study clinic or
in the hospital or at home. The ultrasound uses sound waves to take pictures of the
gallbladder.
Participants will have a physical exam.
Participants will have their mouths looked at for tooth loss, dentures, and gum redness.
Participants will give a blood sample or saliva sample.
Participants will be asked for access to their medical history. They may be asked to allow
researchers to keep any samples taken during gallbladder surgery.
Participants will answer questions about their medical history. This will include illnesses,
surgeries, medicine use, and family history. It will also include diet and lifestyle habits,
such as places where they have lived and worked.
Some participants will have 3 follow-up visits over 6 years.
...
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 precede GDC 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. This approach is reasonable given that the female gender bias for gallbladder cancer is
largely thought to be due to the gender bias for gallstones,1-3 suggesting that in the
presence of gallstones, the risk of gallbladder cancer is the same for men and women. In
addition, Chile is conducting a general population cohort in a small town in the high-risk
area, and we can use the men with gallstones enrolled by the Chilean study to compare to the
women in our 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).
