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Completed

NCT Number: NCT05217433

Oleuropein and Muscle Energy Metabolism

Preclinical studies performed at Nestlé Research (NR) identified oleuropein as a novel activator of mitochondrial calcium import. This potentiated mitochondrial calcium uptake resulted in decreased phosphorylation of the enzyme pyruvate dehydrogenase (PDH), which is linked to its activation as a rate limiting enzyme for mitochondrial oxidation, as well as increasing mitochondrial oxygen consumption, resulting ultimately in decreases in muscle fatigue. In addition, NR demonstrated that during aging, mitochondrial calcium and oxygen consumption rates are decreased in isolated skeletal muscle fibers. The next step in the evidence development is to demonstrate efficacy of oleuropein for improved muscle energy and decreased physical fatigue in a healthy aging population.

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Key information

Conditions

Muscular Fatigue Fatigue Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

50 year–70 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Maastricht University Medical Centre +

Maastricht, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male
  • 50 to 70 years old
  • BMI 18.5-29.9 kg/m2
  • Healthy as per medical history and investigator's/ physician's judgement
  • Having given informed consent

Exclusion criteria

  • Allergy/intolerance to the study product
  • >5% body mass change in the previous 3 months
  • HbA1c ≥ 6.5%
  • Blood pressure >140/90 mmHg
  • Participating in a structured (progressive) exercise program
  • Smoking
  • Diagnosed acute or chronic medical conditions that, in the opinion of the investigator, could impact study outcomes
  • Diagnosed musculoskeletal disorders
  • Chronic use of gastric acid suppressing medication
  • Unauthorized concomitant medications such as calcium antagonists (e.g. valproate), oral corticosteroids, anything that will prevent subjects from safely completing the study according to the investigator or medications / drugs known interfering with the expected mechanism of action of IP or to affect the outcome parameters
  • Alcohol (intake higher than 3 servings per day. One serving is 0.4 dl of alcohol, 1 dl of wine, or 3 dl of beer) or drug abuse
  • Overly imbalanced or restrictive diet (e.g. hyperproteic, vegan, ketogenic, etc.)
  • Subjects not willing and/or not able to comply with scheduled visits and the requirements of the study protocol
  • Any implants that would be a contra-indication for performing an MRI scan.
  • Participation in another study at the same time
  • Blood donation in the past 2 months

Treatment and study plan

Olive leaf extract

Other

The investigational product is a capsule containing 100mg of the active ingredient oleuropein and will be provided once daily in the form of a 250mg olive leaf extract (i.e. 100mg of oleuropein per day) product for the duration of the intervention period (36 days).

Placebo

Other

The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.

Primary outcomes

  1. Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose

    Time frame: Chronic effect after 36 days of intake

    measured by western blotting

  2. Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose

    Time frame: Acute effect after first product intake + chronic effect after 36 days of intake

    measured by biochemical assay analysis

  3. Exploratory outcomes - to evaluate the changes Mitocondrial respiration between oleuropein and placebo groups following 1 single dose

    Time frame: Acute effect after first product intake + chronic effect after 36 days of intake

    measured the rates of oxygen consumption (respiration or JO2) using Oroboros Oxygraph 2K systems with physiological ADP concentrations using permeabilized muscle fibres.

  4. Exploratory outcomes- to evaluate the changes of fatigue between oleuropein and placebo groups following 1 single dose

    Time frame: After 4 weeks of supplementation

    measured using Biodex dynamometer

  5. Exploratory outcomes - to evaluate the changes of fatigue between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured using Biodex dynamometer

  6. Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups

    Time frame: Chronic effect (after 36 days of supplementation)

    measured by western blotting

  7. Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups

    Time frame: Chronic effect (after 36 days of supplementation)

    measured by biochemical assay analysis

  8. Exploratory outcomes - To evaluate the changes of Mitochondrial respiration between oleuropein and placebo groups

    Time frame: Chronic effect (after 36 days of supplementation)

    measured the rates of oxygen consumption (respiration or JO2) using Oroboros Oxygraph 2K systems with physiological ADP concentrations using permeabilized muscle fibres.

Secondary outcomes

  1. Exploratory outcomes - to evaluate the changes of whole body respiratory exchange ratio (RER) between oleuropein and placebo groups following 1 single dose

    Time frame: Acute effect after first product intake+ chronic effect after 36 days of intake

    measured the oxygen and carbon dioxide volume using indirect calorimetry with ventilated hood

  2. Exploratory outcomes - to evaluate the changes of oleuropein metabolites between oleuropein and placebo groups following 1 single dose

    Time frame: Acute effect after first product intake + chronic effect after 36 days of intake

    measured by the analyze of oleuropein metabolites in blood

  3. Exploratory outcomes - to evaluate the changes of glucose concentration between oleuropein and placebo groups following 1 single dose

    Time frame: Acute effect after first product intake + chronic effect after 36 days of intake

    measured by the analyze glucose in blood

  4. Exploratory outcomes - to evaluate the changes Blood glucose, insulin, free fatty acid concentrations -between oleuropein and placebo groups following 1 single dose

    Time frame: Acute effect after first product intake + chronic effect after 36 days of intake

    measured by the analyze of Insulin in blood

  5. Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups following 1 single dose

    Time frame: Acute effect after first product intake + chronic effect after 36 days of intake

    measured by the analyze of free fatty acid concentration (FFA, TG) in blood

  6. Exploratory outcomes - to evaluate the changes of blood pressure between oleuropein and placebo groups following 1 single dose

    Time frame: Acute effect after first product intake + chronic effect after 36 days of intake

    measured using automated inflatable cuff

  7. Exploratory outcomes - to evaluate the changes of anti-inflammatory markers between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured by the analyze of anti-inflammatory markers in blood

  8. Exploratory outcomes - to evaluate the changes of Antioxidant markers between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured by the analyze of antioxidant markers in blood

  9. Exploratory outcomes - to evaluate the changes in glucose concentration between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured by the analyze glucose in blood

  10. Exploratory outcomes - to evaluate the changes of insulin concentration between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured by the analyze of insulin in blood

  11. Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured by the analyze of free fatty acid concentration (FFA, TG) in blood

  12. Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured with the World Health Organisation quality of life questionnaire (WHOQOL-BREF) (rating 0 for 'not at all' and 5 for 'an extreme amount')

  13. Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured with the Profile of Mood States - short-form (POMS-SF) - scale (rating 0 for 'not at all' and 4 for 'extremely')

  14. Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured with the Quality of Life (QoL) questionnaires

  15. Exploratory outcomes - to evaluate the changes in the fatigue perception and mood state pre/post Biodex measurement between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measured with the current mood questionnaire (rating 0 for 'not at all' - 4 for 'extremely')

  16. Exploratory outcomes - to evaluate the changes in the fatigue perception and mood state pre/post Biodex measurement between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    RPE visual analog scale Questionnaire - BORG scale (6 for 'no exertion - 20 for 'maximal exertion'

  17. Exploratory outcomes to evaluate the changes in body composition between oleuropein and placebo groups

    Time frame: Chronic effect (after 29 days of supplementation)

    measure the whole body muscle and fat content using Magnetic resonance imaging (MRI)

  18. Exploratory outcomes - Whole body respiratory exchange ratio - To evaluate the changes of Whole body respiratory exchange ratio (RER) between oleuropein and placebo groups

    Time frame: Chronic effect (after 36 days of supplementation)

    measure the oxygen and dioxygen volume using Indirect calorimetry with ventilation hood

  19. Exploratory outcomes - To evaluate the changes of oleuropein metabolites between oleuropein and placebo groups

    Time frame: Chronic effect (after 36 days of supplementation)

    measure by analyzing Oleuropein metabolites in blood

  20. Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators of muscle metabolism between oleuropein and placebo groups

    Time frame: Chronic effect (after 36 days of supplementation)

    measured by analyzing RNAseq and MS-based proteomics

  21. Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups

    Time frame: Chronic effect (after 36 days of supplementation)

    measured using Western Blot

  22. Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups

    Time frame: Chronic effect (after 36 days of supplementation)

    measured by analyzing polymerase chain reaction

  23. Exploratory outcomes - to evaluate the changes in Strength between oleuropein and placebo groups

    Time frame: After 4 weeks of supplementation

    measured using biodex dynanometer

  24. Exploratory outcomes to evaluate the changes of strenght between oleuropein

    Time frame: Chronic effect (after 29 days of supplementation)

    measured using biodex dynanometer

Sponsors and collaborators

Lead sponsor

Société des Produits Nestlé (SPN)

Industry

Collaborators

  • Maastricht University Medical Center

Registry information

Official study title

A Randomized, Double-blind, Placebo Controlled Study to Investigate the Efficacy of Oleuropein on Skeletal Muscle Energy Metabolism and Fatigue in Humans

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Feb 1, 2022
Registry last updated
Mar 17, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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