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Semaglutide Treatment in the Real-world for Fibrosis Due to NAFLD in Obesity and T2DM (SAMARA)

Primary Purpose

Fibrosis, Liver, Type 2 Diabetes Mellitus in Obese, Non-Alcoholic Fatty Liver Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Semaglutide
Placebo
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fibrosis, Liver

Eligibility Criteria

40 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria: Adult, age ≥ 40 and < 80 years Participant must meet at least one of following sets of conditions: BMI ≥ 27 kg/m² OR BMI ≥ 25 kg/m² AND presence of i) pre-diabetes (HbA1C ≥ 5.7) or ii) type 2 diabetes mellitus (T2DM), as defined by the American Diabetes Association (ADA) clinical practice recommendations. The ADA definition of T2DM is applicable if one of the following criteria is met: Presence of diabetes symptoms (polyuria, polydipsia, polyphagia, increased fatigue, weight loss, blurred vision) and casual plasma glucose ≥ 200 mg/dL (11.1 mmol/L) Fasting plasma glucose (FPG) ≥ 126 mg/dl (7.0 mmol/L) Plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test (OGTT)⁶⁸. If any of the above test results occur, testing should be repeated on a different day to confirm the diagnosis. OR • Hemoglobin A1C (HbA1C) ≥ 6.5% ⁶⁹. FAST score ≥ 0.5 and VCTE ≥ 8.0 kPa; FAST score threshold based on data from MAESTRO-NASH trial⁴²; VCTE cutpoint based on AASLD guidelines for identification of patients with significant fibrosis risk. Participants without a VCTE assessment in their medical record may qualify for the study if they have a FIB-4 ≥ 1.0, which is a cutpoint based on observations of patients with T2DM in Ajmera et al³⁰, and VCTE ≥ 8.0 kPa. The subject is fully informed and willing and able to perform all the procedures specified in the protocol and has signed a written informed consent to participate Exclusion criteria: Presence of regular and/or excessive use of alcohol, defined as > 30 g/day for males and > 20 g/day for females, for a period longer than 2 years at any time in the last 10 years Evidence of cirrhosis or previously known cirrhosis, based on the results from previous liver biopsy or history of portal hypertension presented by ascites, hepatic encephalopathy or varices VCTE ≥ 20 kPa Platelet count ≤ 140,000 per Ml Albumin < 3.6 g/dL INR > 1.35, unless on coumadin for another indication Serum creatinine > 2.0 mg/dL eGFR < 30 mL/min/1.73 m² as defined according to the CKDEPI creatinine equation⁷⁰ Use of other weight loss medications, including GLP1RA within the last 90 days Greater than 10% weight loss in the prior six months Known or suspected hypersensitivity to GLP1RA medications including semaglutide History of bariatric surgery within the past 5 years or expected bariatric surgery Evidence of other causes of chronic liver disease including: Hepatitis B, as defined as presence of hepatitis B surface antigen (HBsAg). Previous or current infection with Hepatitis C, as defined by presence of hepatitis C virus Ab in serum (anti-HCV Ab). Autoimmune hepatitis, as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy. Autoimmune cholestatic liver disorders, as defined by elevation of alkaline phosphatase and anti- mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis. Wilson disease, as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease deficiency, as defined by alpha-1-antitrypsin phenotype and liver histology consistent with alpha-1-antitrypsin deficiency.

Sites / Locations

  • University of California, San DiegoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Semaglutide

Placebo

Arm Description

2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing Semaglutide 3.0 mg/ml for subcutaneous use

2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing 3.0 mg/ml of a placebo solution for subcutaneous use

Outcomes

Primary Outcome Measures

Change in fibrosis due to NAFLD
Change in fibrosis due to Nonalcoholic fatty liver disease (NAFLD), as measured by change in FAST Score, which combines FibroScan results with aspartate aminotransferase (AST).

Secondary Outcome Measures

Change in liver stiffness
Change in liver stiffness, as measured by change in Vibration-Controlled Transient Elastography
Change in steatosis
Change in steatosis, as measure by a change in proton density fat fraction or controlled attenuation parameter
Change in ALT
Change in ALT, as measured by a change in patients with ALT >= 30 U/L at baseline

Full Information

First Posted
August 16, 2023
Last Updated
September 1, 2023
Sponsor
University of California, San Diego
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1. Study Identification

Unique Protocol Identification Number
NCT06005012
Brief Title
Semaglutide Treatment in the Real-world for Fibrosis Due to NAFLD in Obesity and T2DM
Acronym
SAMARA
Official Title
Semaglutide Treatment in the Real-world for Fibrosis Due to NAFLD in Obesity and T2DM
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 25, 2023 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Conduct a community intervention study that will 1) validate a screening approach to identify patients at risk for advanced NAFLD in the obese or T2DM population, and 2) test whether semaglutide treatment is effective for the management of significant fibrosis due to NAFLD in high-risk patients.
Detailed Description
Nonalcoholic fatty liver disease (NAFLD) affects approximately 25-30% of the global population and is projected to become the leading cause of liver transplantation in the United States by 2030. Development of efficient screening strategies for the identification and treatment of individuals who are at greatest risk for advanced disease in this population is an urgent and unmet medical need. Type 2 diabetes mellitus (T2DM) and obesity are critical risk factors for advanced NAFLD. In a prospective cross-sectional study of patients with type 2 diabetes, we screened 524 participants (50-80 years old) with type 2 diabetes mellitus for the presence of NAFLD and observed relative prevalences of 70% for steatosis and 15% for advanced fibrosis. The presence of obesity in this population further increased the odds of advanced fibrosis. These findings suggest that screening populations of individuals with obesity or T2DM may be an effective strategy for identifying high-risk patients with NAFLD. Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) that is FDA-approved for the treatment of obesity (as Wegovy) or T2DM (as Ozempic), conditions that are considered major risk factors for advanced fibrosis in the NAFLD population. It is unclear, however, whether semaglutide is effective for treatment of fibrosis due to NAFLD in these populations. Here, the investigators propose to conduct a community intervention study that will 1) validate a screening approach to identify patients at risk for advanced NAFLD in the obese or T2DM population, and 2) test whether semaglutide treatment is effective for the management of significant fibrosis due to NAFLD in high-risk patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibrosis, Liver, Type 2 Diabetes Mellitus in Obese, Non-Alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Semaglutide
Arm Type
Experimental
Arm Description
2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing Semaglutide 3.0 mg/ml for subcutaneous use
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing 3.0 mg/ml of a placebo solution for subcutaneous use
Intervention Type
Drug
Intervention Name(s)
Semaglutide
Intervention Description
Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) that is FDA-approved for the treatment of obesity (as Wegovy) or T2DM (as Ozempic).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Change in fibrosis due to NAFLD
Description
Change in fibrosis due to Nonalcoholic fatty liver disease (NAFLD), as measured by change in FAST Score, which combines FibroScan results with aspartate aminotransferase (AST).
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Change in liver stiffness
Description
Change in liver stiffness, as measured by change in Vibration-Controlled Transient Elastography
Time Frame
52 weeks
Title
Change in steatosis
Description
Change in steatosis, as measure by a change in proton density fat fraction or controlled attenuation parameter
Time Frame
52 weeks
Title
Change in ALT
Description
Change in ALT, as measured by a change in patients with ALT >= 30 U/L at baseline
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Adult, age ≥ 40 and < 80 years Participant must meet at least one of following sets of conditions: BMI ≥ 27 kg/m² OR BMI ≥ 25 kg/m² AND presence of i) pre-diabetes (HbA1C ≥ 5.7) or ii) type 2 diabetes mellitus (T2DM), as defined by the American Diabetes Association (ADA) clinical practice recommendations. The ADA definition of T2DM is applicable if one of the following criteria is met: Presence of diabetes symptoms (polyuria, polydipsia, polyphagia, increased fatigue, weight loss, blurred vision) and casual plasma glucose ≥ 200 mg/dL (11.1 mmol/L) Fasting plasma glucose (FPG) ≥ 126 mg/dl (7.0 mmol/L) Plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test (OGTT)⁶⁸. If any of the above test results occur, testing should be repeated on a different day to confirm the diagnosis. OR • Hemoglobin A1C (HbA1C) ≥ 6.5% ⁶⁹. FAST score ≥ 0.5 and VCTE ≥ 8.0 kPa; FAST score threshold based on data from MAESTRO-NASH trial⁴²; VCTE cutpoint based on AASLD guidelines for identification of patients with significant fibrosis risk. Participants without a VCTE assessment in their medical record may qualify for the study if they have a FIB-4 ≥ 1.0, which is a cutpoint based on observations of patients with T2DM in Ajmera et al³⁰, and VCTE ≥ 8.0 kPa. The subject is fully informed and willing and able to perform all the procedures specified in the protocol and has signed a written informed consent to participate Exclusion criteria: Presence of regular and/or excessive use of alcohol, defined as > 30 g/day for males and > 20 g/day for females, for a period longer than 2 years at any time in the last 10 years Evidence of cirrhosis or previously known cirrhosis, based on the results from previous liver biopsy or history of portal hypertension presented by ascites, hepatic encephalopathy or varices VCTE ≥ 20 kPa Platelet count ≤ 140,000 per Ml Albumin < 3.6 g/dL INR > 1.35, unless on coumadin for another indication Serum creatinine > 2.0 mg/dL eGFR < 30 mL/min/1.73 m² as defined according to the CKDEPI creatinine equation⁷⁰ Use of other weight loss medications, including GLP1RA within the last 90 days Greater than 10% weight loss in the prior six months Known or suspected hypersensitivity to GLP1RA medications including semaglutide History of bariatric surgery within the past 5 years or expected bariatric surgery Evidence of other causes of chronic liver disease including: Hepatitis B, as defined as presence of hepatitis B surface antigen (HBsAg). Previous or current infection with Hepatitis C, as defined by presence of hepatitis C virus Ab in serum (anti-HCV Ab). Autoimmune hepatitis, as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy. Autoimmune cholestatic liver disorders, as defined by elevation of alkaline phosphatase and anti- mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis. Wilson disease, as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease deficiency, as defined by alpha-1-antitrypsin phenotype and liver histology consistent with alpha-1-antitrypsin deficiency.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Egbert Madamba
Phone
(858) 246-2227
Email
emadamba@health.ucsd.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rohit Loomba
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Egbert Madamba
Phone
858-246-2227
Email
emadamba@health.ucsd.edu

12. IPD Sharing Statement

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Semaglutide Treatment in the Real-world for Fibrosis Due to NAFLD in Obesity and T2DM

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