None listed
Conditions
Brief summary
Metabolic (dysfunction)-associated steatotic liver disease (MASLD) is increasing in prevalence worldwide and is becoming one of the most common indications of liver transplant. Obesity rates are also rising globally and is a common comorbidity in liver transplant recipients. As medical management improves for liver transplant recipients, many achieve long-term survival well beyond 20 years. Obesity-related complications such as cardiovascular disease and cancer are now responsible for an ever-increasing proportion of post-transplant deaths. Development of de novo obesity and metabolic complications including hepatic steatosis is becoming an increasing medical issue following liver transplant, however there is currently no proven intervention to successfully mitigate post-liver transplant hepatic steatosis and obesity, despite aggressive nutritional interventions. The purpose of this study is to identify patients with post-transplant hepatic steatosis and to intervene with pharmacotherapy in the form of subcutaneous semaglutide. We aim to not only reduce hepatic steatosis but also improve the metabolic and cardiovascular risk profile and thereby reduce the incidence of related health conditions that are frequently observed in this population. This study will be a double-blinded randomized controlled trial in post-liver transplant patients with obesity and/or metabolic risk factors. We will study the impact of subcutaneous semaglutide in reducing hepatic steatosis and the impact on body composition, metabolic and cardiovascular disease outcomes.
Interventions
Semaglutide subcutaneous injection up to a maximum of 2.4mg weekly for up to 68 weeks.
Semaglutide will be started at 0.25mg subcutaneous injection weekly, and titrated no sooner than every 4 weeks and until reaching maximal tolerated dose, not exceeding 2.4mg weekly. Dose titration will occur after clinical review with a trial doctor every 4 weeks for the first 16 weeks of the trial to ensure tolerability and no safety concerns prior to each dose escalation.
Trial participants will be taug
Semaglutide subcutaneous injection up to a maximum of 2.4mg weekly for up to 68 weeks. Semaglutide will be started at 0.25mg subcutaneous injection weekly, and titrated no sooner than every 4 weeks and until reaching maximal tolerated dose, not exceeding 2.4mg weekly. Dose titration will occur after clinical review with a trial doctor every 4 weeks for the first 16 weeks of the trial to ensure tolerability and no safety concerns prior to each dose escalation. Trial participants will be taught to self-inject semaglutide by an experienced nurse at the beginning of the study. All participants will undergo supervised nutrition and lifestyle modification by trained dieticians and physiotherapists to assist with weight loss. Adherence to semaglutide will be assessed at frequent follow up phone and face-to-face reviews by study doctors.
Sponsors
Austin Health
Novo Nordisk
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Patients who have undergone liver transplant between 6 months and 5 years prior to enrolment with: • BMI >30 • BMI >27 in conjunction with any additional risk factor for metabolic disease (index liver transplant for NAFLD, diabetes mellitus, hyperlipidemia, personal or first degree family history of coronary artery disease, HTN or past or active smoking status)
Exclusion criteria
• Active cancer • Active infection • Frailty (hand grip strength <2 standard deviations below the age and gender-specified mean) • Age <18 years or >70 years • Prior pancreatitis • Previous bariatric surgery • Use of anti-obesity medication 90 days before enrollment • Use of GLP-1 analogue 90 days before enrollment • Stage 4 chronic kidney disease (eGFR <30mL/min) • Symptomatic New York Heart Association stage III or IV heart failure • Child Pugh B or C cirrhosis • Unable to provide consent
Outcome results
None listed