Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)Phase 2SAMeMASLDc-02NCT07495995
SAMe for Prevention of Liver Cancer in MASLD-Related Cirrhosis
A Phase 2 study testing S-adenosyl-L-methionine (SAMe) and Placabo in people with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), run by Cedars-Sinai Medical Center.
Trial summary
This study will evaluate the safety, feasibility, and preliminary effects of S-adenosyl-L-methionine (SAMe) compared with placebo in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
- What is being tested?
- S-adenosyl-L-methionine (SAMe) and Placabo
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 94 participants
- Where
- No sites listed yet
- Study dates
- 15 Apr 2026to 31 Dec 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- individuals 18 years old or above.
- Understand the study procedures and able to provide informed consent.
- Clinical diagnosis of MASLD per American Association for the Study of Liver Diseases (AASLD) guideline: Patients with hepatic steatosis identified by imaging or biopsy, AND have at least one of five cardiometabolic risk factors:
- BMI ≥25 kg/m2 (23 kg/m2 for Asian) OR waist circumference >94 cm for male or >80 cm for female.
- Fasting serum glucose ≥5.6 mmol/L (100 mg/dL) OR 2-hour post-load glucose levels ≥7.8 mmol/L (140 mg/dL) OR HbA1c ≥5.7% (39 mg/dL) OR type 2 diabetes OR treatment for type 2 diabetes (iii) Blood pressure ≥130/85 mmHg OR specific antihypertensive drug treatment. (iv) Plasma triglycerides ≥1.7 mmol/L (150 mg/dL) OR lipid lowering treatment (v) Plasma HDL-cholesterol ≤1.0 mmol/L (40 mg/dL) for male or ≤1.3 mmol/L (50 mg/dL) for female OR lipid lowering treatment.
- Current weekly intake of alcohol <210 g (7.41 oz) for male or weekly intake of alcohol <140 g (4.76 oz) for female, [1 oz/30 mL of alcohol is present in one 12 oz/360 mL beer, 4 oz/120 mL glass of wine, and a 1oz/30 mL measure of 40 proof (20%) alcohol]
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- Diagnosis of cirrhosis confirmed via histopathology OR at least two of the following measures:
- Transient elastography (FibroScan® ≥ 12 kPa) (ii) Computed tomography (iii) MRI including MR elastography (stiffness ≥ 4.71 kPa) (iv) Abdominal Ultrasound
- Patient had imaging for HCC screening (Ultrasound or MRI or CT) within 3 months prior to screening.
Who cannot join
- Confirmed diagnosis of HCC prior to screening, any suspicious nodules identified prior or during screening must be followed with documentation of HCC negative confirmed prior to randomization.
- History of other causes of liver disease, including but not limited to alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (primary biliary cholangitis, primary sclerosing cholangitis, or autoimmune hepatitis), drug-induced hepatotoxicity, Wilson's disease, iron overload, or alpha-1-antitrypsin deficiency.
- Most recent serum creatinine >1.5 mg/dl within 3 months prior to screening.
- Active infection with positive urine culture, blood culture, or pneumonia at screening.
- History of gastrointestinal bleeding within the prior 28 days
- History of liver transplantation.
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- Women who are pregnant or nursing at screening.
- Significant systemic illness including chronic obstructive pulmonary disease, congestive heart failure, and renal failure that in the opinion of the investigator would preclude the patient from participating in the study or poses a significant risk of mortality during the study period, such as conditions that are interfering with the absorption, distribution, metabolism, or excretion of S-adenosyl-L-methionine (SAMe) such as those with gastric bypass surgery.
- HIV infection or patients who are immunocompromised.
- Participation in another investigational drug, biologic, or medical device trial within 30 days prior to screening.
- Systemic antibiotic use or use of rifaximin for 10 days or more within the last 2 months prior to screening.
- Actively taking investigational or over-the-counter SAMe within 28 days prior to screening.
- Subjects with psychiatric illnesses such as bipolar disorders and Parkinson's disease as SAMe may interfere with the levels of anti-psychotic drugs and might interact with drugs and dietary supplements that increase levels of serotonin (a chemical produced by nerve cells), such as antidepressants, L-tryptophan, and St. John's wort.
- Members from the same family of study participant.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Single-center, Phase II Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Effect of S-adenosyl-L-methionine (SAMe) in Prevention of Hepatocellular Carcinoma Among Patients With Metabolic Dysfunction-associated Steatotic Liver Diseases (MASLD)-Related Cirrhosis
This study will evaluate the safety, feasibility, and preliminary effects of S-adenosyl-L-methionine (SAMe) compared with placebo in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis. Investigators will assess whether treatment is associated with changes in liver-related clinical measures, biologic markers, and other study outcomes relevant to disease progression. The goal of this study is to generate early data to determine whether SAMe should be studied further as a potential therapeutic strategy in patients with MASLD cirrhosis.
Read the detailed description
Patients with MASLD cirrhosis are at risk for progressive liver dysfunction and liver-related complications, and additional treatment strategies are needed. SAMe is a biologically relevant methyl donor with potential effects on liver metabolism, inflammation, and cellular injury pathways. In this study, eligible patients will be assigned to receive SAMe or placebo according to the study protocol. Investigators will evaluate safety, tolerability, study adherence, and changes in prespecified clinical and laboratory outcomes over the treatment period. Results from this study are intended to support the design of future trials and to clarify the potential role of SAMe in patients with MASLD cirrhosis.
- Being tested
- S-adenosyl-L-methionine (SAMe), Placabo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S-adenosyl-L-methionine (SAMe)Drug
Oral S-adenosyl-L-methionine (SAMe) administered at 1,200 mg/day in two divided doses for 12 months. Each tablet provides 400 mg of SAMe (from 800 mg SAMe tosylate disulfate). Participants are instructed to take 2 tablets in the morning before breakfast and 1 tablet in the evening before dinner, approximately 30 minutes before meals.
PlacaboOther
Matching placebo tablets for oral administration, administered on the same schedule as active SAMe for 12 months. Participants are instructed to take 2 tablets in the morning before breakfast and 1 tablet in the evening before dinner, approximately 30 minutes before meals. Placebo tablets are identical or similar to active SAMe tablets in size, color, shape, taste, and odor/appearance to maintain blinding.
| Study group | Role | What they receive |
|---|---|---|
| SAMe | Experimental | Participants will receive oral S-adenosyl-L-methionine (SAMe) 1,200 mg/day in two divided doses for 12 months. Receives: Drug: S-adenosyl-L-methionine (SAMe) |
| Placebo | Placebo comparator | Participants will receive matching placebo for 12 months. Receives: Other: Placabo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Prognostic Liver Secretome signature (PLSec) score
Prognostic Liver Secretome signature (PLSec) is a continuous serum biomarker score used to assess hepatocellular carcinoma risk. Higher PLSec scores indicate higher hepatocellular carcinoma risk, and lower PLSec scores indicate lower hepatocellular carcinoma risk. The primary analysis compares change from baseline to Month 12 between the SAMe and placebo groups. The protocol does not specify a fixed theoretical minimum or maximum PLSec score.
Measured: Baseline to Month 12
Secondary outcomes (1)
Incidence of adverse events and serious adverse events
Safety and tolerability of SAMe will be assessed by collection of adverse events and serious adverse events, graded and monitored per protocol and NCI CTCAE version 5.0.
Measured: Day 0 through 30 days after the last dose of study intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2026
- Study start15 Apr 2026 (estimated)
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)Studies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized 1:1 to receive oral SAMe 1,200 mg/day in two divided doses or matching placebo for 12 months.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 94 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ju Dong Yang, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07495995
- Sponsor's protocol ID
- STUDY00004355
- Acronym
- SAMeMASLDc-02
- Status last verified
- Mar 2026
- First submitted
- 22 Mar 2026
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Phase II Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Effect of S-adenosyl-L-methionine (SAMe) in Prevention of Hepatocellular Carcinoma Among Patients With Metabolic Dysfunction-associated Steatotic Liver Diseases (MASLD)-Related Cirrhosis
- ClinicalTrials.gov ID
- NCT07495995
- Acronym / sponsor ID
- SAMeMASLDc-02 / STUDY00004355
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 94 participants (estimated)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Study start
- 15 Apr 2026 (estimated)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 27 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety, feasibility, and preliminary effects of S-adenosyl-L-methionine (SAMe) compared with placebo in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis. Investigators will assess whether treatment is associated with changes in liver-related clinical measures, biologic markers, and other study outcomes relevant to disease progression. The goal of this study is to generate early data to determine whether SAMe should be studied further as a potential therapeutic strategy in patients with MASLD cirrhosis.
Detailed description
Patients with MASLD cirrhosis are at risk for progressive liver dysfunction and liver-related complications, and additional treatment strategies are needed. SAMe is a biologically relevant methyl donor with potential effects on liver metabolism, inflammation, and cellular injury pathways. In this study, eligible patients will be assigned to receive SAMe or placebo according to the study protocol. Investigators will evaluate safety, tolerability, study adherence, and changes in prespecified clinical and laboratory outcomes over the treatment period. Results from this study are intended to support the design of future trials and to clarify the potential role of SAMe in patients with MASLD cirrhosis.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Participants will be randomized 1:1 to receive oral SAMe 1,200 mg/day in two divided doses or matching placebo for 12 months.
| Arm | Type | Receives |
|---|---|---|
| SAMe | Experimental | Drug: S-adenosyl-L-methionine (SAMe)Participants will receive oral S-adenosyl-L-methionine (SAMe) 1,200 mg/day in two divided doses for 12 months. |
| Placebo | Placebo comparator | Other: PlacaboParticipants will receive matching placebo for 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- individuals 18 years old or above.
- Understand the study procedures and able to provide informed consent.
- Clinical diagnosis of MASLD per American Association for the Study of Liver Diseases (AASLD) guideline: Patients with hepatic steatosis identified by imaging or biopsy, AND have at least one of five cardiometabolic risk factors:
- Current weekly intake of alcohol <210 g (7.41 oz) for male or weekly intake of alcohol <140 g (4.76 oz) for female, [1 oz/30 mL of alcohol is present in one 12 oz/360 mL beer, 4 oz/120 mL glass of wine, and a 1oz/30 mL measure of 40 proof (20%) alcohol]
- Diagnosis of cirrhosis confirmed via histopathology OR at least two of the following measures:
Key exclusion criteria (14 listed)
- Confirmed diagnosis of HCC prior to screening, any suspicious nodules identified prior or during screening must be followed with documentation of HCC negative confirmed prior to randomization.
- History of other causes of liver disease, including but not limited to alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (primary biliary cholangitis, primary sclerosing cholangitis, or autoimmune hepatitis), drug-induced hepatotoxicity, Wilson's disease, iron overload, or alpha-1-antitrypsin deficiency.
- Most recent serum creatinine >1.5 mg/dl within 3 months prior to screening.
- Active infection with positive urine culture, blood culture, or pneumonia at screening.
- History of gastrointestinal bleeding within the prior 28 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| S-adenosyl-L-methionine (SAMe)Oral S-adenosyl-L-methionine (SAMe) administered at 1,200 mg/day in two divided doses for 12 months. Each tablet provides 400 mg of SAMe (from 800 mg SAMe tosylate disulfate). Participants are instructed to take 2 tablets in the morning before breakfast and 1 tablet in the evening before dinner, approximately 30 minutes before meals. | Drug | SAMe |
| PlacaboMatching placebo tablets for oral administration, administered on the same schedule as active SAMe for 12 months. Participants are instructed to take 2 tablets in the morning before breakfast and 1 tablet in the evening before dinner, approximately 30 minutes before meals. Placebo tablets are identical or similar to active SAMe tablets in size, color, shape, taste, and odor/appearance to maintain blinding. | Other | Placebo |
Primary outcome
Change in Prognostic Liver Secretome signature (PLSec) score
Time frame: Baseline to Month 12
Prognostic Liver Secretome signature (PLSec) is a continuous serum biomarker score used to assess hepatocellular carcinoma risk. Higher PLSec scores indicate higher hepatocellular carcinoma risk, and lower PLSec scores indicate lower hepatocellular carcinoma risk. The primary analysis compares change from baseline to Month 12 between the SAMe and placebo groups. The protocol does not specify a fixed theoretical minimum or maximum PLSec score.
1 secondary outcome
Incidence of adverse events and serious adverse events
Time frame: Day 0 through 30 days after the last dose of study intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing S-adenosyl-L-methionine (SAMe) and Placabo in people with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), run by Cedars-Sinai Medical Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ju Dong Yang, MD (3109677454, judong.yang@cshs.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Prognostic Liver Secretome signature (PLSec) score (time frame: Baseline to Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026; AzTrials last refreshed its copy on 8 Nov 2026.