TOTUM-448 for Fatty Liver Disease

(CARDIO-LIVER Trial)

Overseen By Véronique Sapone, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Valbiotis

Must not be taking: Study outcome affecting drugs

Disqualifiers: Metabolic disorders, Uncontrolled hypertension, ASCVD, others

Compensation: Varies

Number of Visits: 6

Duration: 16 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new blend of five plant extracts and choline, called TOTUM-448, might reduce liver fat and improve heart health and gut balance in people with fatty liver disease. Participants will take this mix twice a day to determine its effectiveness compared to a placebo. The trial seeks individuals diagnosed with fatty liver disease, with a BMI between 25 and 40, and stable weight over the last three months. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatments for fatty liver disease.

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.

Is there any evidence suggesting that TOTUM-448 is likely to be safe for humans?

Research has shown that TOTUM-448, a combination of plant extracts and choline, has been safe in earlier studies. These studies did not find any major side effects, and participants generally tolerated the treatment well. TOTUM-448 has been used to lower liver fat and reduce inflammation in people with liver problems without causing serious issues. This suggests the treatment could be safe for broader use. Participants have not experienced serious problems, which is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for fatty liver disease, which often focus on lifestyle changes or medications like vitamin E and pioglitazone, TOTUM-448 is derived from plant-based active ingredients. Researchers are excited about TOTUM-448 because it offers a new approach by potentially targeting the metabolic pathways involved in liver fat accumulation. This could provide a novel and natural option for managing fatty liver disease, setting it apart from conventional therapies that primarily address symptoms rather than the underlying causes.

What evidence suggests that TOTUM-448 might be an effective treatment for fatty liver disease?

Studies have shown that TOTUM-448, a combination of five plant extracts and choline, effectively reduces liver fat. Research indicates that it lowers liver inflammation and improves overall liver health. In animal studies, TOTUM-448 improved sugar metabolism and reduced high insulin levels, both crucial for metabolic health. Initial findings suggest it may help manage fatty liver disease by addressing these key areas. Although more human data is needed, these early results are promising for those with fatty liver disease. Participants in this trial will receive either TOTUM-448 or a placebo to further evaluate its effectiveness in managing the condition. ^{1 2 4 5 6}

Who Is on the Research Team?

André Marette, PhD

Principal Investigator

Laval University

Are You a Good Fit for This Trial?

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.

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• TOTUM-448

Trial Overview 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.

How Is the Trial Designed?

Group I: TOTUM-448 Experimental Treatment 1 Intervention

The experimental active arm will be supplemented with TOTUM-448 twice per day.

Group II: Placebo Placebo Group 1 Intervention

The placebo comparator arm will be supplemented with a placebo twice per day.

Who Is Running the Clinical Trial?

Valbiotis

Lead Sponsor

Trials

13

Recruited

2,000+

Valbiotis Canada inc.

Collaborator

Trials

2

Recruited

90+

Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Collaborator

Trials

26

Recruited

6,300+

CHU de Quebec-Universite Laval

Collaborator

Trials

177

Recruited

110,000+

Laval University

Collaborator

Trials

439

Recruited

178,000+

Published Research Related to This Trial

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the USA, primarily linked to insulin resistance and obesity, leading to conditions like steatosis and cirrhosis.

Weight loss and pharmacologic treatments targeting insulin resistance are key strategies for managing NAFLD, with bariatric surgery showing effectiveness; however, no specific medications are approved yet, though thiazolidinediones and statins show promise in improving liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of non-alcoholic fatty liver disease. Tolman, KG., Dalpiaz, AS.[2022]

In a study of 288 patients with non-alcoholic fatty liver disease (NAFLD), key prognostic criteria for diagnosing the disease and assessing the risk of progression to liver fibrosis were identified, including body mass index and atherogenicity coefficient, which showed high specificity (97.8%) and sensitivity (96.2%).

The study also found that elevated insulin and triglyceride levels were significant indicators for predicting the progression of NAFLD to liver fibrosis, with a specificity of 93.8% and sensitivity of 85.7%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical and prognostic value of metabolic disorders in non-alcoholic fatty liver disease]. Vakhrushev, YM., Suchkova, EV., Lukashevich, АР.[2021]

Vitamin E and pioglitazone have established efficacy in treating nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease (NAFLD), but there are currently no approved pharmacotherapies for NAFLD itself.

Several innovative therapies targeting different pathways of NASH are in development, including agents like obeticholic acid and elafibranor, with four promising candidates currently undergoing phase 3 trials, which may provide new treatment options in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future pharmacological therapies for NAFLD/NASH. Sumida, Y., Yoneda, M.[2023]

In a 36-week study involving 125 patients with biopsy-confirmed NASH, resmetirom significantly reduced hepatic fat compared to placebo, with a 32.9% reduction at 12 weeks and 37.3% at 36 weeks, indicating its efficacy in treating NASH.

The treatment was generally safe, with most adverse events being mild or moderate; however, there was a higher incidence of mild diarrhea and nausea in patients taking resmetirom.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Harrison, SA., Bashir, MR., Guy, CD., et al.[2021]

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder globally, often linked to obesity and insulin resistance, and is characterized by excess fat accumulation in the liver, primarily in the form of triglycerides.

Steatosis, the initial stage of NAFLD, is reversible through lifestyle changes, but if left untreated, it can progress to more severe liver conditions like steatohepatitis, fibrosis, and cirrhosis, highlighting the importance of early intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatty Acids and Effects on In Vitro and In Vivo Models of Liver Steatosis. Vergani, L.[2019]

Citations

1. nature.com nature.com/articles/s44355-025-00033-z

The polyphenol-rich plant extract Totum-448 decreases ... In the present study, we aimed to investigate the effects of Totum-448 on hepatic steatosis, liver inflammation, and metabolic homeostasis in a ...

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06704321

NCT06704321 | Effects of TOTUM-448 on Liver Fat ... Study Overview. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12403019/

Totum‐448 Improves MASLD and Modulates Microbiota in ... It is a progressive disease that begins with simple lipid infiltration in the hepatocytes (steatotic liver disease) before advancing to MASH ( ...

4. biorxiv.org biorxiv.org/content/10.1101/2025.03.24.644956v1.full.pdf

Totum-448, a polyphenol-rich plant extract, decreases ... We found that Totum-448 13 significantly lowered hyperinsulinemia and systemic glucose intolerance in MASLD mice 14 without affecting body weight, fat mass, ...

5. biospace.com biospace.com/valbiotis-will-present-significant-preclinical-results-for-its-active-substance-totum-448-against-fatty-liver-diseases-nafl-and-nash-at-the-annual-meeting-of-the-american-association-for-the-study-of-liver-diseases-aasld

448 Against Fatty Liver Diseases (NAFL and NASH), at the ... By the end of the study, TOTUM•448 had reduced the level of fat in the liver (steatosis), but also reduced immune markers of liver inflammation ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/562335

Effects of TOTUM-448 on Liver Fat Content ... 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 ...