In this study, semaglutide will be compared to placebo (a look-alike inactive substance, a "sugar pill") to determine if its use will prevent weight gain after liver transplantation (LT). In addition, researchers will be testing to determine if semaglutide prevents the development of Non-Alcoholic Fatty Liver Disease (NAFLD) after transplant through Magnetic Resonance Imaging (MRI) and laboratory results.
Weight gain following LT is common and a risk for cardiovascular disease and development of NAFLD. Developing NAFLD following LT can lead to patients developing scar tissue in the graft (transplanted liver), and graft-cirrhosis. These events can limit the benefit of the transplanted liver graft and reduce the benefit of LT as a therapy. Current weight management strategies have not been successful at the prevention of these events in most patients. This highlights a substantial unmet need for effective treatment to prevent or reduce post-LT weight gain and highlight the importance of new treatment strategies for reducing illness, death, and healthcare cost associated with post-LT weight gain. The purpose of this research study is to test the safety, tolerability, and effectiveness of semaglutide when used to prevent weight gain after liver transplant. Semaglutide is a drug that has been approved by the U. S. Food and Drug Administration (FDA) for treatment of obesity and Type 2 Diabetes. Semaglutide, has shown to be effective for not only weight loss but also long-term weight maintenance. Semaglutide has also shown to be helpful in treatment of nonalcoholic steatohepatitis (NASH) in the non-transplant population. This medication also is used to control blood sugar and prevent cardiovascular disease, which contributes to poor outcomes in LT recipients. Thus, the purpose of the present study is to determine if use of semaglutide early after LT can (1) reduce weight gain and (2) prevent development of NAFLD following LT.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Starting dose of 0.24 mg injected weekly and increased every 4 weeks to a potential maximum dose of 2.4 mg weekly at 20 weeks followed by 52 weeks of weekly injections at the maximum tolerable dose
Placebo solution injected weekly for 72 weeks
Virginia Commonwealth University
Richmond, Virginia, United States
RECRUITINGChange in weight
Weight measured in kilograms
Time frame: Baseline to week 72
Development of NAFLD
Number of participant who develop NAFLD by the end of treatment will be measured via MRI-PDFF (MRI-Proton Density Fat Fraction). A value of \>5.2% will be considered the threshold for development of NAFLD following LT.
Time frame: Week 72
Change in adiposity
Fat distribution of the body body (body composition) will be assessed via MRI (i.e. visceral adipose tissue, abdominal subcutaneous tissue, fat free muscle volume, and muscle fat infiltration, epicardial fat). Means of delta body composition measures after 72 weeks will be compared between the two arms.
Time frame: Baseline to week 72
Change in insulin resistance
Frequently Sampled IV Glucose Tolerance Test (FSIVGTT) will be used to measure insulin resistance
Time frame: Baseline to week 72
Change in inflammation - C-reactive protein (CRP)
Level of CRP will be assessed using a standard blood test.
Time frame: Baseline to week 72
Change in inflammation - adiponectin
Level of adiponectin will be assessed using a standard blood test.
Time frame: Baseline to week 72
Change in liver fibrosis markers
Fibrosis-4 (FIB-4) Index for Liver Fibrosis and NAFLD Fibrosis Score (NFS) will be assessed using a standard blood test.
Time frame: Baseline to week 72
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Enrollment
50
Change in serum lipid profile
Cardiovascular risk factors will be assessed using a standard lipid panel blood test.
Time frame: Baseline to week 72