Betaine vs. Placebo for Serologically Diagnosed Metabolic Dysfunction-associated Steatohepatitis (MASH)

Inclusion Criteria

• •Patients must satisfy all the following criteria to be eligible for enrollment.
• •1. Outpatient
• •2. Receiving health care at a clinical site that is participating in this trial.
• •3. A clinical diagnosis of metabolic dysfunction-associated steatotic liver disease based in having 1 or more components of the metabolic syndrome.
• •4. ALT ≥50 U/L on the most recent measurement and within 28 days prior to randomization
• •5. NIS2+ ≥0.6815 within 60 days prior to randomization
• •6. Age 18 to 75 years (inclusive).
• •7. BMI≥28.
• •8. MRI PDFF ≥10%.
• •9. Participants with type 2 diabetes must be receiving stable doses of medicines for the 4 months prior to randomization.
• •10. Ability to consume oral medication and willing to adhere to the study medicine regimen.
• •11. Stated willingness to comply with all study procedures, including returning study medicines at each clinic visit, and availability for the duration of the trial.
• •12. Agreement to adhere to comprehensive lifestyle modification (involving nutrition, exercise, and behavior modification) throughout study duration.
• •13. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 weeks after the end of study medicine administration (ie, after the Week 24 study visit).
• •14. Provision of a signed and dated informed consent form.
• •An individual who meets any of the following criteria will be excluded from participating in this trial.
• •1. Use of FDA-approved medications for the treatment of MASH within the prior 6 months or anticipated to use an FDA-approved medications for MASH during the next 12 months.
• •2. Use of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or GLP-1/GIP receptor agonist in the prior 6 months or anticipated use during the next 12 months.
• •3. Use of a medicine designed to reduce weight within the prior 6 months or anticipated use in the next 12 months.
• •4. Received insulin within the past 90 days or anticipation of needing insulin in the next 6 months.
• •5. Uncontrolled diabetes defined as HbA1c of 9.5% or higher within 60 days prior to enrollment.
• •6. Unstable body weight defined as \>5% self-reported (or documented) change in body weight in the period in the 90 days prior to screening.
• •7. Moderate or heavy alcohol more than 1 week/month during the 3 months prior to screening. Moderate alcohol use is defined as more than 20 g/day (\>14 drinks/week) in females or more than 30 g/day (\>21 drinks per week) in males. A drink is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80-proof spirits, or the equivalent amount of alcohol in other alcoholic drinks.
• •8. Phosphatidylethanol (PEth) test \> 50 ug/L. (NOTE: PEth will be performed at screening. Participants with PEth \>50 ug/L will be excluded. Repeat testing of PEth in participants with a PEth \>50 ug/L at screening is not permitted.)
• •9. Inability to reliably quantify alcohol consumption based upon local study physician judgement.
• •10. Use of corticosteroids at a does equal to or greater than 10 mg/day of prednisone, for more than 5 days within the prior 30 days.
• •11. Continued use of drugs historically associated with NAFLD (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins) for more than 2 weeks in the 6 months prior to randomization.
• •12. Cirrhosis of the liver, defined as any of the following: