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Muscular FatigueNCT05217433

Oleuropein and Muscle Energy Metabolism

A study testing Olive leaf extract in people with Muscular Fatigue, run by Société des Produits Nestlé (SPN) at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 50 to 70 years, men onlyHealthy volunteers can take part
Conditions the study is for
Muscular Fatigue
What is being tested?
Olive leaf extract
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
1 siteNetherlands
Study dates
4 Nov 2021to 10 Mar 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 70 years
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 16Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • Maastricht University Medical Centre +

    Maastricht

Other trials in Netherlands

About this study

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

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.

Being tested
Olive leaf extract, Placebo
Keywords
Skeletal muscle energy and fatigue
Medical subject headings
Fatigue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Olive leaf extractOther

    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).

  • PlaceboOther

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

Study groups in NCT05217433
Study groupRoleWhat they receive
Investigational productExperimentalThe 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).
Receives: Other: Olive leaf extract
Control armPlacebo comparatorThe control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    measured by western blotting

    Measured: Chronic effect after 36 days of intake

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

    measured by biochemical assay analysis

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

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

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

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

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

    measured using Biodex dynamometer

    Measured: After 4 weeks of supplementation

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

    measured using Biodex dynamometer

    Measured: Chronic effect (after 29 days of supplementation)

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

    measured by western blotting

    Measured: Chronic effect (after 36 days of supplementation)

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

    measured by biochemical assay analysis

    Measured: Chronic effect (after 36 days of supplementation)

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

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

    Measured: Chronic effect (after 36 days of supplementation)

Secondary outcomes (24)
  1. Exploratory outcomes - to evaluate the changes of whole body respiratory exchange ratio (RER) between oleuropein and placebo groups following 1 single dose

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

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

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

    measured by the analyze of oleuropein metabolites in blood

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

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

    measured by the analyze glucose in blood

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

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

    measured by the analyze of Insulin in blood

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

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

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

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

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

    measured using automated inflatable cuff

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

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

    measured by the analyze of anti-inflammatory markers in blood

    Measured: Chronic effect (after 29 days of supplementation)

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

    measured by the analyze of antioxidant markers in blood

    Measured: Chronic effect (after 29 days of supplementation)

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

    measured by the analyze glucose in blood

    Measured: Chronic effect (after 29 days of supplementation)

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

    measured by the analyze of insulin in blood

    Measured: Chronic effect (after 29 days of supplementation)

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

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

    Measured: Chronic effect (after 29 days of supplementation)

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

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

    Measured: Chronic effect (after 29 days of supplementation)

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

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

    Measured: Chronic effect (after 29 days of supplementation)

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

    measured with the Quality of Life (QoL) questionnaires

    Measured: Chronic effect (after 29 days of supplementation)

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

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

    Measured: Chronic effect (after 29 days of supplementation)

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

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

    Measured: Chronic effect (after 29 days of supplementation)

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

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

    Measured: Chronic effect (after 29 days of supplementation)

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

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

    Measured: Chronic effect (after 36 days of supplementation)

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

    measure by analyzing Oleuropein metabolites in blood

    Measured: Chronic effect (after 36 days of supplementation)

  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

    measured by analyzing RNAseq and MS-based proteomics

    Measured: Chronic effect (after 36 days of supplementation)

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

    measured using Western Blot

    Measured: Chronic effect (after 36 days of supplementation)

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

    measured by analyzing polymerase chain reaction

    Measured: Chronic effect (after 36 days of supplementation)

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

    measured using biodex dynanometer

    Measured: After 4 weeks of supplementation

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

    measured using biodex dynanometer

    Measured: Chronic effect (after 29 days of supplementation)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2022
  2. Study start4 Nov 2021
  3. Primary completion10 Mar 2023
  4. Study completion10 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a single-centre, double-blind, placebo controlled, randomised 2-arms parallel group study.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05217433
Sponsor's protocol ID
20.22.NRC
Status last verified
Mar 2023
First submitted
25 Nov 2021
Last updated
17 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Pinckaers PJ, Petrick HL, Horstman AM, Moreno-Asso A, De Marchi U, Hendriks FK, Kuin LM, Fuchs CJ, Grathwohl D, Verdijk LB, Zorenc AH, Senden JM, Migliavacca E, Metairon S, Poquet L, Morin-Rivron D, Karagounis LG, Holloway GP, Feige JN, van Loon LJ. Oleuropein Supplementation Increases Resting Skeletal Muscle Fractional Pyruvate Dehydrogenase Activity but Does Not Influence Whole-Body Metabolism: A Randomized, Double-Blind, and Placebo-Controlled Trial in Healthy, Older Males. J Nutr. 2025 May;155(5):1373-1386. doi: 10.1016/j.tjnut.2025.02.015. Epub 2025 Feb 22.

    PubMed 39993475

Questions about this trial

What is this clinical trial studying?

A study testing Olive leaf extract in people with Muscular Fatigue, run by Société des Produits Nestlé (SPN) at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05217433, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2023.

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