Determination of Biological Activity of Enriched Serum Following TOTUM-448 Consumption (CnC-TOTUM448)

Determination of Biological Activity of Enriched Serum Among Healthy Participants After Consumption of the Food Supplement TOTUM-448

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.

Study Overview

• Status: Completed
• Conditions: NAFLD; MASLD; Mild Inflammatory Context
• Intervention / Treatment: Dietary supplement: TOTUM-448

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • University Hospital Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Main Inclusion Criteria:

• 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

Main Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TOTUM-448; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to reach the maximum concentration in serum of detectable polyphenol metabolite concentrations by UPLC-MS/MS.	After ingestion of TOTUM-448 the concentration in serum of detectable polyphenol metabolites will be assessed every 20 minutes during 240 minutes.	From timepoint 0 minute to timepoint 240 minutes.

Collaborators and Investigators

• Sponsor: Valbiotis
• Collaborators: University Hospital, Clermont-Ferrand; Clinic'n'Cell
• Investigators: Principal Investigator: Gisèle Pickering, PhD, University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2023
• Primary Completion (Actual): January 8, 2024
• Study Completion (Actual): April 11, 2024

Study Registration Dates

• First Submitted: September 5, 2023
• First Submitted That Met QC Criteria: September 14, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2024
• Last Update Submitted That Met QC Criteria: May 29, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: lipid metabolism; inflammation; oxidative stress; polyphenols; plant extract; hepatocytes; ex vivo; dietary/food supplement
• Other Study ID Numbers: 2023-A00579-36

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No