Background:
In non-alcoholic fatty liver disease (NAFLD), fat accumulates in the liver and can cause damage. Researchers want to learn what causes the damage NAFLD, and to see if a medication can help.
Objective:
To find out how the liver in people with NAFLD responds to feeding, and how this relates to their response to the drug semaglutide.
Eligibility:
People with NAFLD and healthy volunteers ages 18 and older
Design:
Participants will be screened with:
Medical history
Physical exam
Blood tests
Imaging: A machine will take pictures of the participant s body.
Within 2-8 weeks of enrollment, participants will stay in the clinic for several days. This includes:
Blood, urine, heart, and imaging tests
For NAFLD participants only: A needle-like device will remove a small biopsy of the liver and fatty tissue.
Participants will be alone in a special room for 5 hours. They will breathe through a tube under the nostrils. They will have blood drawn several times.
The baseline visit concludes participation for healthy volunteers but NAFLD participants will contine.
About 6 weeks after discharge, participants will stay in the clinic again and repeat the tests. They will get their first semaglutide dose by injection.
Participants will have visits weeks 1, 2, 4, 8, 12, 16, 20, and 24 of treatment. Visits include blood tests.
Participants will inject semaglutide once a week at home.
At week 30, participants will stay in the clinic again and repeat the tests.
Participants will have a final visit 12 weeks after stopping treatment. This includes blood and urine tests.
...
Male or female Aged >= 18 years of age.
Histological evidence of hepatic steatosis on a liver biopsy within 12 months OR evidence of fatty liver disease, as documented by imaging (ultrasound, CT, MRI, MRI-PDFF, MR spectroscopy, or Fibroscan CAP >= 285 db/M25) within 12 months.
Estimated average alcohol consumption < 30 g/d for men or < 20 g/d for women in the 6 months prior to enrollment and no binge-drinking behavior.
Ability of subject to understand and the willingness to sign a written informed consent document.
Pregnant or breast-feeding
Chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who were treated successfully for HCV and achieved sustained virological response can be eligible for enrollment > 18 months after treatment cessation. Patients receiving antiviral therapy are ineligible.
HIV infection.
Concomitant liver disease such as autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson s disease, alpha-1 antitrypsin deficiency, hereditary hemochromatosis.
Parallel
Semaglutide
DrugSemaglutide injection once weekly
Histological Improvement
\>= point decrease in NAFLD activity score (range 0-8, high scores indicate more activity)
Clinical Improvement
Reduction of liver fat content (measure with 1H-magnetic resonance spectroscopy) by \>= 25% and reduction of ALT by \>=25% or normalization of ALT
Change in hepatic gene expression
Change in hepatic gene expression for biopsies performed at baseline and 2 hours after an oral 75g glucose load
Click on the lead sponsor to view all of their trials.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Lead sponsor
National Cancer Institute (NCI)
Collaborator
