Actively Recruiting
Non-Alcoholic Fatty Liver Disease, the Hepatic Response to Oral Glucose, and the Effect of Semaglutide (NAFLD HEROES)
Led by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · Updated on 2026-05-12
84
Participants Needed
1
Research Sites
4 weeks
Total Duration
On this page
Sponsors
N
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic steatohepatitis (NASH), involve fat buildup in the liver that can cause damage. Researchers want to understand how the liver responds to eating in people with NAFLD and how this relates to their reaction to the drug semaglutide, which is being studied to assess its effects on this condition. This study focuses on exploring liver responses and identifying predictors for treatment response in NAFLD patients. Participants include adults with NAFLD and healthy volunteers. The study involves screening with medical history, physical exams, blood tests, and imaging. NAFLD participants undergo liver biopsies before and after an oral glucose load, followed by treatment with weekly semaglutide injections for 30 weeks. Healthy volunteers complete initial assessments but do not receive treatment. There are multiple clinic visits for testing, biopsies, and monitoring throughout the study. During participation, individuals will stay in the clinic several times for blood, urine, heart, and imaging tests, including breathing tests during a 5-hour observation. Blood samples are collected multiple times, and biopsies are taken for NAFLD patients. Follow-up visits include blood and urine tests after treatment ends. Researchers measure liver tissue changes, gene expression, and clinical improvement, with safety and response monitored throughout the study period up to 12 weeks after treatment stops.
CONDITIONS
Brief Title
Non-Alcoholic Fatty Liver Disease, the HEpatic Response to Oral Glucose, and the Effect of Semaglutide (NAFLD HEROES)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Male or female aged 18 years or older
- Histological evidence of hepatic steatosis on liver biopsy within 12 months or fatty liver disease confirmed by imaging within 12 months
- Average alcohol consumption less than 30 g/day for men or less than 20 g/day for women in the past 6 months without binge drinking
- Ability and willingness to sign informed consent
- Presence of NAFLD with steatosis grade ≥1 on baseline liver biopsy for treatment phase
- Liver fat content ≥10% by 1H-MRS on initial admission
- Healthy volunteers must be 18 or older with no liver disease, normal BMI (≤25 kg/m2), non-diabetic, and normal liver enzyme and glucose levels
- Ability and willingness to sign informed consent
You will not qualify if you...
- Pregnant or breastfeeding
- Chronic hepatitis B or C infection or ongoing antiviral therapy
- HIV infection
- Other liver diseases such as autoimmune hepatitis or Wilson's disease
- Drug-induced liver injury or unstable liver enzyme levels due to medication
- Advanced liver disease with specific lab or clinical criteria
- Use of medications causing fatty liver disease
- Uncontrolled thyroid disorders or suspicious thyroid nodules
- Active coronary artery disease or congestive heart failure
- Chronic kidney disease with reduced kidney function
- Uncontrolled diabetes with HbA1c over 9%
- Use of certain diabetes medications unless discontinued 3 months prior
- Contraindications to liver biopsy or MRI
- History of bariatric surgery or malabsorption
- Use of orlistat or treatment for NAFLD unless stable or withdrawn 3 months prior
- Recent liver biopsy unless willing to undergo study biopsies
- Allergy to study medication
- Alcohol or substance abuse within past 12 months
- Women of childbearing potential unwilling to use contraception
- Personal or family history of medullary thyroid carcinoma or MEN-2
- Active intensive weight loss efforts or recent significant weight loss
- Recent investigational drug use
- Investigator judgment of unsuitability for study participation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Within 1 week
Participants undergo liver biopsies in fasting state and 2 hours after an oral 75g glucose load to assess liver tissue response.
2 visits (in-person liver biopsies)
Duration - 30 weeks
Participants receive semaglutide injection once weekly to treat NAFLD for 30 weeks.
Weekly visits for medication administration and monitoring
Duration - Within 2 weeks after treatment
Participants undergo a final liver biopsy and assessments to evaluate clinical response and liver changes after treatment.
1 visit (in-person liver biopsy and assessments)
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
Y
Yaron Rotman, M.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
BASIC_SCIENCE
Number of Arms
3
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