Determination of Biological Activity of Enriched Serum Following TOTUM-448 Consumption

NCT06047847 | Completed

• 1 other identifier: 2023-A00579-36
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Dietary intakes of saturated fatty acids remain well above nutritional recommendations for most European countries. This may progressively lead to a pro-inflammatory context and the alteration of lipid metabolism in the liver. The hypothesis of this study is that TOTUM-448 promotes the normal function of hepatocytes in a mild inflammatory context. To determine the cellular and molecular effects of TOTUM-448, circulating bioactive molecules after TOTUM-448 intake will be collected and then studied in human hepatocytes using an innovative ex vivo clinical approach developed by Clinic'n'Cell.

Conditions

NAFLD; MASLD; Mild Inflammatory Context

Keywords

ex vivo; lipid metabolism; inflammation; hepatocytes; oxidative stress; plant extract; polyphenols; dietary/food supplement

Outcome Measures

Primary Outcomes (5)

• Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on viability of human hepatocytes in a hyperlipidic pro-inflammatory context.

  Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max.

  At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes.

• Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on cholesterol storage of human hepatocytes in a hyperlipidic pro-inflammatory context.

  Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max.

  At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes.

• Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on triglyceride storage of human hepatocytes in a hyperlipidic pro-inflammatory context.

  Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max.

  At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes.

• Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on oxidative stress status of human hepatocytes in a hyperlipidic pro-inflammatory context.

  Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max.

  At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes.

• Evaluate the influence of circulating bioactive metabolites in blood stream resulting from the intake of TOTUM-448 on pro-inflammatory cytokine expression of human hepatocytes in a hyperlipidic pro-inflammatory context.

  Naïve will be compared to enriched serum from the 10 healthy participants at the previously determined t-max.

  At phenolic compounds t-max obtained during kinetic phase. Note: According to previous studies, t-max is expected around 60 minutes.

Secondary Outcomes (1)

• Time to reach the maximum concentration in serum of detectable polyphenol metabolite concentrations by UPLC-MS/MS.

  From timepoint 0 minute to timepoint 240 minutes.

Study Arms (1)

TOTUM-448

EXPERIMENTAL

10 healthy men will consume an acute intake of 4.284g of TOTUM-448 on three separate occasions. Phase 1: once per galenic form (capsule and powder). Phase 2: once (capsule only).

Dietary Supplement: TOTUM-448

Interventions

TOTUM-448 DIETARY_SUPPLEMENT

The study is divided in two phases. The first clinical phase of the project is aimed at determining TOTUM-448's metabolites absorption peak (two galenic forms will be tested: capsules and powder). Then, human circulating metabolites from polyphenols will be quantified and characterized by ultra-high performance liquid chromatography hyphenated with tandem mass spectrometry (UPLC-MS/MS). Once the absorption profile is characterized, volunteers will visit once again the clinical center for the collection of serum fractions either naïve (before ingestion) or enriched (containing circulating metabolites following TOTUM-448 ingestion). The enriched fraction (circulating bioactive collection) will be collected at t-max as characterized in the first phase (absorption profil's peak). Finally, biological activity of TOTUM-448 on human hepatocytes will be studied by comparing naïve serum and serum containing circulating metabolites according to an in vitro protocol.

TOTUM-448

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Lipid profile within reference values
• Glycemia \< 100mg/dL
• Normal hepatic function
• Normal blood formulation
• Normal renal function
• BMI between 20 and 28kg/m2
• Non smoker or occasional smoker

You may not qualify if:

• All types of vaccination within one month
• Alcohol intakes superior to World Health Organization recommendations
• Ongoing pharmacological, dietary supplement and/or probiotic treatment
• Any known disease
• Allergy to ingredients of the study product
• With dietary habits incompatible with the study conduct

Sponsors & Collaborators

• Valbiotis: lead
• Clinic'n'Cell: collaborator
• University Hospital, Clermont-Ferrand: collaborator

Study Sites (1)

University Hospital Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

Related Publications (1)

• Wauquier F, Boutin-Wittrant L, Krisa S, Valls J, Langhi C, Otero YF, Sirvent P, Peltier S, Bargetto M, Cazaubiel M, Sapone V, Bouchard-Mercier A, Roux V, Macian N, Pickering G, Wittrant Y. Circulating Human Metabolites Resulting from TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons from an Original Ex Vivo Clinical Trial. Nutrients. 2023 Apr 14;15(8):1903. doi: 10.3390/nu15081903.

  PMID: 37111121 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Inflammation

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gisèle Pickering, PhD

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: An ex vivo clinical approach.

Study Record Dates

• First Submitted: September 5, 2023
• First Posted: September 21, 2023
• Study Start: September 27, 2023
• Primary Completion: January 8, 2024
• Study Completion: April 11, 2024
• Last Updated: May 31, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)