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 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. ^{1 2 3 4 5}

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 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]

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]

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 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]

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]

Citations

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

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

2. Japan pubmed.ncbi.nlm.nih.gov

Current and future pharmacological therapies for NAFLD/NASH. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Treatment of non-alcoholic fatty liver disease. [2022]

4. England 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. [2021]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinical and prognostic value of metabolic disorders in non-alcoholic fatty liver disease]. [2021]