Clinical trial NCT06983171: Semaglutide Effectiveness in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease in the Real World Practice
Official title: Real-World Clinical Practice Study on the Effectiveness of Semaglutide Over 154 Weeks in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: MAFLD
Keywords: CTT-003
Semaglutide in MAFLD
Lead sponsor: Center of target therapy
Sponsor class: OTHER
First posted: 2025-05-21
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will enroll adults aged 18-70 years with obesity (BMI \>30 kg/m²) and hepatic steatosis (CAP \>238 dB/m) confirmed within 3 months. Eligible participants must have metabolic dysfunction-associated fatty liver disease (MAFLD) without other chronic liver conditions (e.g., viral hepatitis, cirrhosis complications like ascites, or MELD score \>12).

Brief summary: This real-world clinical trial evaluates the effectiveness of semaglutide (target dose is 2.4 mg/week) over 154 weeks (3 years) prescribed to the patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis (stages 0-4) as a part of routine clinical practice. MAFLD is a common liver condition linked to obesity, type 2 diabetes (T2DM), and metabolic syndrome, which can progress to severe liver damage (cirrhosis) and heart disease. Currently, there are no approved medications for MAFLD, and treatment relies on lifestyle changes. Semaglutide, a GLP-1 receptor agonist, has shown promise in improving liver health and metabolic markers in earlier studies.

Detailed description: - What is this study about?

This real-world clinical trial evaluates the effectiveness of semaglutide (in target dose of 2.4 mg/week) over 154 weeks (3 years) prescribed to the patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis (stages 0-4) as a part of routine clinical practice.. MAFLD is a common liver condition linked to obesity, type 2 diabetes (T2DM), and metabolic syndrome, which can progress to severe liver damage (cirrhosis) and heart disease. Currently, there are no approved medications for MAFLD, and treatment relies on lifestyle changes. Semaglutide, a GLP-1 receptor agonist, has shown promise in improving liver health and metabolic markers in earlier studies.

- Why is this study important? MAFLD affects 24% of adults globally, with 20% progressing to advanced stages (MASH/cirrhosis).

MAFLD increases risks of liver failure, cardiovascular disease, and is a leading cause for liver transplants.

- Semaglutide may help by: Reducing liver fat and inflammation. Improving weight, blood sugar, and cholesterol. Slowing liver fibrosis progression.

* Study Details Participants: 70 adults with MAFLD and liver fibrosis (stages 0-4).
* Treatment: Semaglutide (target dose is 2.4 mg/week; however, the dose may be lower in case of poor tolerance or safety concerns).
* Duration: 154 weeks.
* Assessments:

Liver biopsies (to measure inflammation/fibrosis). MRI and elastography (non-invasive liver fat/stiffness tests). Blood tests (liver enzymes, cholesterol, HbA1c). Weight and cardiovascular health monitoring.

- Patient Participation Patients will attend the clinic per the routine clinical practice (it is anticipated that there will be approx. 10 visits over 3 years, with phone check-ins between visits).

Treatment will be conducted in accordance with the local label and routine clinical practice.

* Potential Benefits Access to a promising therapy for MAFLD. Close monitoring of liver and metabolic health. Contribution to advancing MAFLD treatment options.
* Risks and Considerations Semaglutide may cause nausea, diarrhea, or other side effects (typically mild). Liver biopsy carries minimal risks (e.g., pain, bleeding).

Eligibility criteria: Inclusion Criteria:

* Informed consent obtained before performing any research-related action. Research-related procedures include any procedures conducted within the framework of this study, including activities to assess eligibility criteria for participation in the study.
* Body Mass Index (BMI) \> 30 kg/m².
* CAP test result \> 238 dB/m based on steatometry performed no later than 3 months before the patient is included in the study.
* Age 18-70 years at the time of signing the informed consent.

Exclusion Criteria:

* Any contraindication to the appointment of semaglutide.
* Documented reasons for chronic liver disease other than non-alcoholic fatty liver disease (NAFLD).
* Positive test result for HBsAg, HIV antibodies, or positive test result for HCV-RNA.
* Presence of ascites, bleeding from esophageal varices, hepatic encephalopathy, spontaneous bacterial peritonitis, or liver transplantation at the time of screening or a history of these conditions.
* ALT activity \> 5 times the upper limit of normal (ULN).
* AST activity \> 5 times the ULN.
* Alkaline phosphatase activity \> 2 times the ULN at screening.
* International Normalized Ratio (INR) of prothrombin time ≥ 1.35 at screening.
* MELD score \> 12 points at screening.
* Platelet count less than 150,000 per microliter of blood, unless it reflects the patient's usual platelet level, and the patient does not have a diagnosis of portal hypertension in the investigator's opinion.
* Treatment with GLP-1 receptor agonists within 90 days prior to the screening visit.
* Treatment with hypolipidemic drugs or weight loss medications, whose dosage has not been stable, in the investigator's opinion, for 90 days prior to the screening visit.
* Previous or planned (during the study period) treatment of obesity with surgical intervention or the installation of a special device for weight loss. However, the following procedures are allowed:

  1. Liposuction and/or abdominoplasty, if performed more than 1 year before screening.
  2. Laparoscopic gastric banding, if the band was removed more than 1 year before baseline liver biopsy and screening.
  3. Intragastric balloon placement, if the balloon was removed more than 1 year before baseline liver biopsy and screening.
  4. Duodenojejunal sleeve bypass, if the sleeve was removed more than 1 year before baseline liver biopsy and screening.
* Presence of malignant neoplasms currently or in history within the last 5 years prior to screening. Exceptions include only basal cell or squamous cell skin cancer and any carcinoma in situ.
* History of acute pancreatitis within 180 days prior to inclusion in the study.
* Presence of chronic pancreatitis currently or in history.
* Any of the following: myocardial infarction, stroke, heart failure of NYHA class IV, hospitalization for unstable angina, or transient ischemic attack within the last 90 days before the screening day.
* Any health disorder that, in the investigator's opinion, could jeopardize patient safety or affect compliance with the protocol requirements.

Primary outcomes:
measure: Evaluate the impact of semaglutide therapy on liver morphological changes based on liver histology using the NAFLD Activity Score (NAS).
timeFrame: 154 weeks
measure: Evaluate the impact of semaglutide therapy on the degree of steatosis change based on Controlled Attenuation Parameter (CAP score)
timeFrame: 154 weeks
measure: Evaluate the impact of semaglutide therapy on the degree and distribution of fat infiltration in the liver based on MR spectroscopy data
timeFrame: 154 weeks
measure: Evaluate the impact of semaglutide therapy on changes in liver elasticity based on elastography data
timeFrame: 154 weeks
Secondary outcomes:
measure: Evaluate the impact of semaglutide therapy on patients' body weight
timeFrame: 154 weeks
measure: Evaluate the impact of semaglutide therapy on changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels
timeFrame: 154 weeks
measure: Evaluate the impact of semaglutide therapy on changes in Total Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein (HDL) Cholesterol and Triglycerides levels
timeFrame: 154 weeks
measure: Evaluate the impact of semaglutide therapy on changes in High-sensitivity C-reactive Protein (hs-CRP) level
timeFrame: 154 weeks
measure: Evaluate the time to the first cardiovascular event during semaglutide therapy
timeFrame: 154 weeks
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Center of Target Therapy LLC.
Study officials:
affiliation: Center of target therapy
name: Pavel Bogomolov, Prof., PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: