TOTUM-448 for Fatty Liver Disease
(CARDIO-LIVER Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Valbiotis
Must not be taking: Study outcome affecting drugs
Disqualifiers: Metabolic disorders, Uncontrolled hypertension, ASCVD, others
Trial Summary
What is the purpose of this trial?This clinical trial aims to investigate the effects of TOTUM-448, a mix of 5 plant extracts and choline, consumed at the daily regimen of two times per day, on liver fat content, cardiometabolic risk factors and gut microbiota among both men and women with MASLD.
Will I have to stop taking my current medications?
The trial requires that participants do not take medications that may affect the study outcomes, so you might need to stop certain medications. It's best to discuss your current medications with the trial team to see if they are allowed.
How is the treatment TOTUM-448 unique for fatty liver disease?
TOTUM-448 is unique because it is a novel treatment specifically being studied for fatty liver disease, a condition with no approved pharmacotherapy. Unlike other treatments that target insulin resistance or dyslipidemia, TOTUM-448 may offer a new approach, although specific details about its mechanism or components are not provided in the available research.
12345Eligibility Criteria
This trial is for men and women with MASLD, a condition related to Non-alcoholic Fatty Liver Disease. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study.Inclusion Criteria
Weight stable within ± 5% in the last three months
BMI ≥25 and <40 kg/m2 and WC thresholds according to the NAFLD Nomenclature consensus group
My liver is mostly healthy with minimal scarring.
+1 more
Exclusion Criteria
I have a history of heart and blood vessel disease.
Contraindications to MRI, Fibroscan® and DEXA
Suffering from a metabolic disorder susceptible to significantly affect glucose metabolism or plasma lipid levels or that might affect the study outcomes according to the investigator
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Baseline
Baseline measurements are taken before the start of supplementation
1 week
1 visit (in-person)
Treatment
Participants receive TOTUM-448 or placebo twice per day for 16 weeks
16 weeks
3 visits (in-person) at 8 weeks and 16 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
1 visit (in-person)
Participant Groups
The trial tests TOTUM-448, which is a combination of five plant extracts and choline taken twice daily, against a placebo. It aims to see if it can reduce liver fat content, improve cardiometabolic risk factors, and alter gut microbiota in MASLD patients.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: TOTUM-448Experimental Treatment1 Intervention
The experimental active arm will be supplemented with TOTUM-448 twice per day.
Group II: PlaceboPlacebo Group1 Intervention
The placebo comparator arm will be supplemented with a placebo twice per day.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Institut sur la nutrition et les aliments fonctionnels (INAF)Québec, Canada
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Who Is Running the Clinical Trial?
ValbiotisLead Sponsor
Valbiotis Canada inc.Collaborator
Institut universitaire de cardiologie et de pneumologie de Québec, University LavalCollaborator
CHU de Quebec-Universite LavalCollaborator
Laval UniversityCollaborator
References
Fatty Acids and Effects on In Vitro and In Vivo Models of Liver Steatosis. [2019]Fatty liver, or steatosis, is a condition of excess accumulation of lipids, mainly under form of triglycerides (TG), in the liver, and it is the hallmark of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disorder world-wide and it has frequently been associated with obesity, hyperlipidemia and insulin resistance. Free fatty acids (FA) are the major mediators of hepatic steatosis; patients with NAFLD have elevated levels of circulating FA that correlate with disease severity.
Current and future pharmacological therapies for NAFLD/NASH. [2023]Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. The efficacy of vitamin E and pioglitazone has been established in nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD. GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes, have shown early efficacy in NASH, and also have beneficial cardiovascular or renal effects. Innovative NASH therapies include four main pathways. The first approach is targeting hepatic fat accumulation. Medications in this approach include modulation of peroxisome proliferator-activator receptors (e.g., pemafibrate, elafibranor), medications targeting farnesoid X receptor axis [obeticholic acid; OCA)], inhibitors of de novo lipogenesis (aramchol, ACC inhibitor), and fibroblast growth factor-21 analogues. A second target is oxidative stress, inflammation, and apoptosis. This class of drug includes apoptosis signaling kinase 1 (ASK1) inhibitor and emricasan (an irreversible caspase inhibitor). A third target is intestinal microbiomes and metabolic endotoxemia. Several agents are in ongoing trials, including IMMe124, TLR4 antagonist, and solithromycin (macrolide antibiotics). The final target is hepatic fibrosis, which is strongly associated with all-cause or liver-related mortality in NASH. Antifibrotic agents are a cysteine-cysteine motif chemokine receptor-2/5 antagonist (cenicriviroc; CVC) and galectin 3 antagonist. Among a variety of medications in development, four agents such as OCA, elafibranor, ASK1 inhibitor, and CVC are currently being evaluated in an international phase 3 trial for the treatment of NASH. Within the next few years, the availability of therapeutic options for NASH will hopefully curb the rising trend of NASH-related diseases.
Treatment of non-alcoholic fatty liver disease. [2022]Non-alcoholic fatty liver disease, defined as the presence of macrovascular steatosis in the presence of less than 20 gm of alcohol ingestion per day, is the most common liver disease in the USA. It is most commonly associated with insulin resistance/type 2 diabetes mellitus and obesity. It is manifested by steatosis, steatohepatitis, cirrhosis, and, rarely, hepatocellular carcinoma.Hepatic steatosis results from an imbalance between the uptake of fat and its oxidation and export. Insulin resistance, predisposing to lipolysis of peripheral fat with mobilization to and uptake of fatty acids by the liver, is the most consistent underlying pathogenic factor. It is not known why some patients progress to cirrhosis; however, the induction of CYP 2E1 with generation of reactive oxygen species appears to be important.Treatment is directed at weight loss plus pharmacologic therapy targeted toward insulin resistance or dyslipidemia. Bariatric surgery has proved effective. While no pharmacologic therapy has been approved, emerging data on thiazolidinediones have demonstrated improvement in both liver enzymes and histology. There are fewer, but promising data, with statins which have been shown to be hepatoprotective in other liver diseases. The initial enthusiasm for ursodeoxycholic acid has not been supported by histologic studies.
Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. [2021]Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation, hepatocellular injury, and progressive liver fibrosis. Resmetirom (MGL-3196) is a liver-directed, orally active, selective thyroid hormone receptor-β agonist designed to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity. We aimed to assess the safety and efficacy of resmetirom in patients with NASH.
[Clinical and prognostic value of metabolic disorders in non-alcoholic fatty liver disease]. [2021]A comprehensive assessment of metabolic parameters in patients with non-alcoholic fatty liver disease and based on them the development of prognostic criteria for the development of liver fibrosis.