- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05217433
Oleuropein and Muscle Energy Metabolism
March 16, 2023 updated by: Société des Produits Nestlé (SPN)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Luc van Loon
- Phone Number: +31 43 388 2222
- Email: l.vanloon@maastrichtuniversity.nl
Study Locations
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Maastricht, Netherlands
- Maastricht University Medical Centre +
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
50 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Male
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Investigational product
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).
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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).
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Placebo Comparator: Control arm
The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.
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The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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measured by western blotting
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Chronic effect after 36 days of intake
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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
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measured by biochemical assay analysis
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Acute effect after first product intake + chronic effect after 36 days of intake
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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
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measured the rates of oxygen consumption (respiration or JO2) using Oroboros Oxygraph 2K systems with physiological ADP concentrations using permeabilized muscle fibres.
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Acute effect after first product intake + chronic effect after 36 days of intake
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Exploratory outcomes- to evaluate the changes of fatigue between oleuropein and placebo groups following 1 single dose
Time Frame: After 4 weeks of supplementation
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measured using Biodex dynamometer
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After 4 weeks of supplementation
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Exploratory outcomes - to evaluate the changes of fatigue between oleuropein and placebo groups
Time Frame: Chronic effect (after 29 days of supplementation)
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measured using Biodex dynamometer
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Chronic effect (after 29 days of supplementation)
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Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
Time Frame: Chronic effect (after 36 days of supplementation)
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measured by western blotting
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Chronic effect (after 36 days of supplementation)
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Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
Time Frame: Chronic effect (after 36 days of supplementation)
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measured by biochemical assay analysis
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Chronic effect (after 36 days of supplementation)
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Exploratory outcomes - To evaluate the changes of Mitochondrial respiration between oleuropein and placebo groups
Time Frame: Chronic effect (after 36 days of supplementation)
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measured the rates of oxygen consumption (respiration or JO2) using Oroboros Oxygraph 2K systems with physiological ADP concentrations using permeabilized muscle fibres.
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Chronic effect (after 36 days of supplementation)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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measured the oxygen and carbon dioxide volume using indirect calorimetry with ventilated hood
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Acute effect after first product intake+ chronic effect after 36 days of intake
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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
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measured by the analyze of oleuropein metabolites in blood
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Acute effect after first product intake + chronic effect after 36 days of intake
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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
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measured by the analyze glucose in blood
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Acute effect after first product intake + chronic effect after 36 days of intake
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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
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measured by the analyze of Insulin in blood
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Acute effect after first product intake + chronic effect after 36 days of intake
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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
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measured by the analyze of free fatty acid concentration (FFA, TG) in blood
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Acute effect after first product intake + chronic effect after 36 days of intake
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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
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measured using automated inflatable cuff
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Acute effect after first product intake + chronic effect after 36 days of intake
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Exploratory outcomes - to evaluate the changes of anti-inflammatory markers between oleuropein and placebo groups
Time Frame: Chronic effect (after 29 days of supplementation)
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measured by the analyze of anti-inflammatory markers in blood
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Chronic effect (after 29 days of supplementation)
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Exploratory outcomes - to evaluate the changes of Antioxidant markers between oleuropein and placebo groups
Time Frame: Chronic effect (after 29 days of supplementation)
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measured by the analyze of antioxidant markers in blood
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Chronic effect (after 29 days of supplementation)
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Exploratory outcomes - to evaluate the changes in glucose concentration between oleuropein and placebo groups
Time Frame: Chronic effect (after 29 days of supplementation)
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measured by the analyze glucose in blood
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Chronic effect (after 29 days of supplementation)
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Exploratory outcomes - to evaluate the changes of insulin concentration between oleuropein and placebo groups
Time Frame: Chronic effect (after 29 days of supplementation)
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measured by the analyze of insulin in blood
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Chronic effect (after 29 days of supplementation)
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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)
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measured by the analyze of free fatty acid concentration (FFA, TG) in blood
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Chronic effect (after 29 days of supplementation)
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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)
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measured with the World Health Organisation quality of life questionnaire (WHOQOL-BREF) (rating 0 for 'not at all' and 5 for 'an extreme amount')
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Chronic effect (after 29 days of supplementation)
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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)
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measured with the Profile of Mood States - short-form (POMS-SF) - scale (rating 0 for 'not at all' and 4 for 'extremely')
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Chronic effect (after 29 days of supplementation)
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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)
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measured with the Quality of Life (QoL) questionnaires
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Chronic effect (after 29 days of supplementation)
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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)
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measured with the current mood questionnaire (rating 0 for 'not at all' - 4 for 'extremely')
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Chronic effect (after 29 days of supplementation)
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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)
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RPE visual analog scale Questionnaire - BORG scale (6 for 'no exertion - 20 for 'maximal exertion'
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Chronic effect (after 29 days of supplementation)
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Exploratory outcomes to evaluate the changes in body composition between oleuropein and placebo groups
Time Frame: Chronic effect (after 29 days of supplementation)
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measure the whole body muscle and fat content using Magnetic resonance imaging (MRI)
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Chronic effect (after 29 days of supplementation)
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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)
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measure the oxygen and dioxygen volume using Indirect calorimetry with ventilation hood
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Chronic effect (after 36 days of supplementation)
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Exploratory outcomes - To evaluate the changes of oleuropein metabolites between oleuropein and placebo groups
Time Frame: Chronic effect (after 36 days of supplementation)
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measure by analyzing Oleuropein metabolites in blood
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Chronic effect (after 36 days of supplementation)
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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)
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measured by analyzing RNAseq and MS-based proteomics
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Chronic effect (after 36 days of supplementation)
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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)
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measured using Western Blot
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Chronic effect (after 36 days of supplementation)
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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)
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measured by analyzing polymerase chain reaction
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Chronic effect (after 36 days of supplementation)
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Exploratory outcomes - to evaluate the changes in Strength between oleuropein and placebo groups
Time Frame: After 4 weeks of supplementation
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measured using biodex dynanometer
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After 4 weeks of supplementation
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Exploratory outcomes to evaluate the changes of strenght between oleuropein
Time Frame: Chronic effect (after 29 days of supplementation)
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measured using biodex dynanometer
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Chronic effect (after 29 days of supplementation)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Luc van Loon, Maastricht University Medical Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 4, 2021
Primary Completion (Actual)
March 10, 2023
Study Completion (Actual)
March 10, 2023
Study Registration Dates
First Submitted
November 25, 2021
First Submitted That Met QC Criteria
January 19, 2022
First Posted (Actual)
February 1, 2022
Study Record Updates
Last Update Posted (Actual)
March 17, 2023
Last Update Submitted That Met QC Criteria
March 16, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20.22.NRC
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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