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

NAFLD Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05424003
• Other study ID #: HM20024306
• Status: Recruiting
• Phase: Phase 2
• Start date: February 22, 2024
• Est. completion date: February 2026

Study information

• Verified date: April 2024
• Source: Virginia Commonwealth University
• Contact: Sherry Boyett, RN
• Phone: 804-828-5434
• Email: sherry.boyett[@]vcuhealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

• 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

Related Conditions & MeSH terms

• NAFLD
• Weight Gain

Intervention

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
• Placebo
Placebo solution injected weekly for 72 weeks

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in weight	Weight measured in kilograms	Baseline to week 72
Secondary	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
Secondary	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
Secondary	Change in insulin resistance	Frequently Sampled IV Glucose Tolerance Test (FSIVGTT) will be used to measure insulin resistance	Baseline to week 72
Secondary	Change in inflammation - C-reactive protein (CRP)	Level of CRP will be assessed using a standard blood test.	Baseline to week 72
Secondary	Change in inflammation - adiponectin	Level of adiponectin will be assessed using a standard blood test.	Baseline to week 72
Secondary	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
Secondary	Change in serum lipid profile	Cardiovascular risk factors will be assessed using a standard lipid panel blood test.	Baseline to week 72