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Study Purpose:
We would like to see whether restoring leptin levels
to normal in eligible patients with fatty liver disease,
who have undergone our Phase I study, will improve
the disease process in these patients.
Research Abstract:
Nonalcoholic steatohepatitis (or NASH) is known to
be caused by deposition of fat in the liver and development
of scarring. This condition occurs more frequently
in overweight and obese persons. It is often associated
with resistance to the actions of insulin hormone.
Fat cells secrete a hormone called leptin. Recently,
we have learned that obese or overweight persons make
too much leptin, which may contribute to insulin resistance.
Paradoxically, patients who do not have any fat cells,
also have insulin resistance. In these patients, insulin
resistance is caused by the absence of leptin and
leptin replacement significantly improves insulin
resistance and fat deposition in the liver. In an
earlier study, we determined the leptin levels in
patients with NASH and how these levels are related
to body fat levels as well as responsiveness to insulin.
We saw that a subgroup of patients with NASH have
relatively low levels of leptin in contrast to the
amount of body fat they had. We now would like to
see if restoring leptin levels to normal will improve
the disease process in these patients. Our study patients
will be male patients, aged between 18 and 65 (inclusive),
who do not have any other cause for their liver disease.
We have put some restrictions in body size such that
a spectrum of patients from normal weight to obese
range would be included. They will also demonstrate
low leptin levels (levels similar to only 25% of normal
population). We will use a genetically engineered
form of leptin manufactured by Amylin Inc. given via
injections under the skin. We plan to continue therapy
for a period of one year and evaluate the change in
liver disease by a liver biopsy. We will also follow
the metabolic parameters and body composition characteristics
that we examined in our Phase I study. We expect that
patients with low blood leptin levels will show improvement
in their liver disease and insulin resistance when
their blood leptin levels are restored to normal.
Eligibility Criteria:
Must have undergone our Phase I study and have
biopsy proven NASH
Demonstrated low leptin levels
Male patients between the age of 18 and 65
We exclude all patients with other known causes
of liver disease
Patients with advanced liver disease are also
ineligible
We exclude patients with diabetes mellitus
and those who are pregnant or lactating
Patients with complicated diseases such as
kidney or heart failure are ineligible
Compensation: $30 per visit
Duration of study: 18 months for each subject
If you are interested in participating as a subject
in this study, please contact Dr. Oral's study coordinator,
Annie Boullion, at (734) 615-0539.
Contact Us:
We are located on the 3rd floor of the Taubman Center,
in the University of Michigan Hospital.
Our address is:
The Department of Internal Medicine
Division of Metabolism, Endocrinology and Diabetes
3920 Taubman Center, SPC 5354
1500 E. Medical Center Drive
Ann Arbor, MI 48109
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