Randomized Double Blinded Placebo-Controlled w/Semaglutide to Prevent Weight Gain After Liver Transplant

A Randomized Double Blinded Placebo-Controlled Trial of Semaglutide to Prevent Weight Gain Following Liver Transplantation

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.

Study Overview

• Status: Recruiting
• Conditions: NAFLD
• Intervention / Treatment: Drug: Semaglutide Pen Injector; Drug: Placebo

Detailed Description

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
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sherry Boyett, RN; Phone Number: 804-828-5434; Email: sherry.boyett@vcuhealth.org
• Study Contact Backup: Name: Mohammad S Siddiqui, MD; Email: mohammad.siddiqui@vcuhealth.org

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female age 18-75 years who received LT for any indication (i.e. NASH, hepatitis C, alcohol-induced cirrhosis, autoimmune hepatitis, etc.)
• Liver transplant surgery within 8-24 weeks prior to randomization
• Fasting glucose > 125 mg/dL or presence of diabetes (HbA1c≥6.5% or use of diabetes medications) or pre-diabetes (HbA1c >5.7%)
• Ability to provide informed consent
• Discharged from the hospital following LT surgery
• Tolerating diet
• Normal graft function* (determined by treating hepatologist/surgeon based on clinical status and hepatic panel)
• Stable immunosuppression according the VCU (Virginia Commonwealth University) post-LT protocols ** (i.e. calcineurin inhibitors + mycophenolate)
• Eligible female patients will be (1) non-pregnant, evidenced by a negative urine pregnancy test, (2) non-lactating, (3)surgically sterile or post-menopausal, or they will agree to continue to use an accepted method of birth control during the study

Exclusion Criteria:

• BMI≤ 27kg/m2
• GFR (Glomerular Filtration Rate) ≤ 25 ml/min/1.73m2
• Type 1 autoimmune diabetes (by anti-GAD (glutamic acid decarboxylase) or history of ketoacidosis)
• History of gastroparesis
• Familial or personal history of medullary thyroid cancer or MEN (Multiple Endocrine Neoplasia) 2
• History of pancreatitis
• History of active malignancy post- LT with the exception of non-melanoma skin cancers
• History of uncontrolled or unstable diabetic retinopathy or maculopathy
• Acute cellular rejection
• Hepatic artery thrombosis
• Medical non-compliance
• Active treatment with GLP (glucagon-like peptide)-1RA (receptor agonist) or SGLT (sodium-glucose cotransporter)-2 inhibitors at time of screening
• History of hypersensitivity to semaglutide or its excipients
• Women who are nursing, pregnant, or planning to become pregnant during the study, or are not using adequate contraceptive measures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide; Semaglutide administered subcutaneously (under the skin) once weekly. There will be a 20 week lead in period of dose escalation before reaching the target dose of 2.4mg weekly. Semaglutide will then be administered at the maximum tolerated dose for 52 weeks.	Drug: Semaglutide Pen Injector; 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; Other Names: Wegovy
Placebo Comparator: Placebo; Placebo administered subcutaneously (under the skin) once weekly.	Drug: Placebo; Placebo solution injected weekly for 72 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in weight	Weight measured in kilograms	Baseline to week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline to week 72
Change in insulin resistance	Frequently Sampled IV Glucose Tolerance Test (FSIVGTT) will be used to measure insulin resistance	Baseline to week 72
Change in inflammation - C-reactive protein (CRP)	Level of CRP will be assessed using a standard blood test.	Baseline to week 72
Change in inflammation - adiponectin	Level of adiponectin will be assessed using a standard blood test.	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.	Baseline to week 72
Change in serum lipid profile	Cardiovascular risk factors will be assessed using a standard lipid panel blood test.	Baseline to week 72

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: Novo Nordisk A/S
• Investigators: Principal Investigator: Mohammad S Siddiqui, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Liver Transplant
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide
• Other Study ID Numbers: HM20024306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No