Back to resultsOleuropein and Muscle Energy Metabolism
Primary Purpose
Muscular Fatigue
Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Olive leaf extract
Placebo
Sponsored by
About this trial
This is an interventional other trial for Muscular Fatigue focused on measuring Skeletal muscle energy and fatigue
Eligibility Criteria
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
Sites / Locations
- Maastricht University Medical Centre +
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Investigational product
Control arm
Arm Description
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).
The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.
Outcomes
Primary Outcome Measures
Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose
measured by western blotting
Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose
measured by biochemical assay analysis
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.
Exploratory outcomes- to evaluate the changes of fatigue between oleuropein and placebo groups following 1 single dose
measured using Biodex dynamometer
Exploratory outcomes - to evaluate the changes of fatigue between oleuropein and placebo groups
measured using Biodex dynamometer
Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
measured by western blotting
Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
measured by biochemical assay analysis
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.
Secondary Outcome Measures
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
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
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
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
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
Exploratory outcomes - to evaluate the changes of blood pressure between oleuropein and placebo groups following 1 single dose
measured using automated inflatable cuff
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
Exploratory outcomes - to evaluate the changes of Antioxidant markers between oleuropein and placebo groups
measured by the analyze of antioxidant markers in blood
Exploratory outcomes - to evaluate the changes in glucose concentration between oleuropein and placebo groups
measured by the analyze glucose in blood
Exploratory outcomes - to evaluate the changes of insulin concentration between oleuropein and placebo groups
measured by the analyze of insulin in blood
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
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')
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')
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
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')
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'
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)
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
Exploratory outcomes - To evaluate the changes of oleuropein metabolites between oleuropein and placebo groups
measure by analyzing Oleuropein metabolites in blood
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
Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups
measured using Western Blot
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
Exploratory outcomes - to evaluate the changes in Strength between oleuropein and placebo groups
measured using biodex dynanometer
Exploratory outcomes to evaluate the changes of strenght between oleuropein
measured using biodex dynanometer
Full Information
NCT ID
NCT05217433
First Posted
November 25, 2021
Last Updated
March 16, 2023
Sponsor
Société des Produits Nestlé (SPN)
Collaborators
Maastricht University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT05217433
Brief Title
Oleuropein and Muscle Energy Metabolism
Official Title
A Randomized, Double-blind, Placebo Controlled Study to Investigate the Efficacy of Oleuropein on Skeletal Muscle Energy Metabolism and Fatigue in Humans
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
November 4, 2021 (Actual)
Primary Completion Date
March 10, 2023 (Actual)
Study Completion Date
March 10, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Société des Produits Nestlé (SPN)
Collaborators
Maastricht University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Fatigue
Keywords
Skeletal muscle energy and fatigue
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This is a single-centre, double-blind, placebo controlled, randomised 2-arms parallel group study.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
This is a single-centre, double-blind, placebo controlled, randomised 2-arms parallel group study.
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Investigational product
Arm Type
Experimental
Arm Description
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).
Arm Title
Control arm
Arm Type
Placebo Comparator
Arm Description
The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.
Intervention Type
Other
Intervention Name(s)
Olive leaf extract
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.
Primary Outcome Measure Information:
Title
Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose
Description
measured by western blotting
Time Frame
Chronic effect after 36 days of intake
Title
Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose
Description
measured by biochemical assay analysis
Time Frame
Acute effect after first product intake + chronic effect after 36 days of intake
Title
Exploratory outcomes - to evaluate the changes Mitocondrial respiration between oleuropein and placebo groups following 1 single dose
Description
measured the rates of oxygen consumption (respiration or JO2) using Oroboros Oxygraph 2K systems with physiological ADP concentrations using permeabilized muscle fibres.
Time Frame
Acute effect after first product intake + chronic effect after 36 days of intake
Title
Exploratory outcomes- to evaluate the changes of fatigue between oleuropein and placebo groups following 1 single dose
Description
measured using Biodex dynamometer
Time Frame
After 4 weeks of supplementation
Title
Exploratory outcomes - to evaluate the changes of fatigue between oleuropein and placebo groups
Description
measured using Biodex dynamometer
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
Description
measured by western blotting
Time Frame
Chronic effect (after 36 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
Description
measured by biochemical assay analysis
Time Frame
Chronic effect (after 36 days of supplementation)
Title
Exploratory outcomes - To evaluate the changes of Mitochondrial respiration between oleuropein and placebo groups
Description
measured the rates of oxygen consumption (respiration or JO2) using Oroboros Oxygraph 2K systems with physiological ADP concentrations using permeabilized muscle fibres.
Time Frame
Chronic effect (after 36 days of supplementation)
Secondary Outcome Measure Information:
Title
Exploratory outcomes - to evaluate the changes of whole body respiratory exchange ratio (RER) between oleuropein and placebo groups following 1 single dose
Description
measured the oxygen and carbon dioxide volume using indirect calorimetry with ventilated hood
Time Frame
Acute effect after first product intake+ chronic effect after 36 days of intake
Title
Exploratory outcomes - to evaluate the changes of oleuropein metabolites between oleuropein and placebo groups following 1 single dose
Description
measured by the analyze of oleuropein metabolites in blood
Time Frame
Acute effect after first product intake + chronic effect after 36 days of intake
Title
Exploratory outcomes - to evaluate the changes of glucose concentration between oleuropein and placebo groups following 1 single dose
Description
measured by the analyze glucose in blood
Time Frame
Acute effect after first product intake + chronic effect after 36 days of intake
Title
Exploratory outcomes - to evaluate the changes Blood glucose, insulin, free fatty acid concentrations -between oleuropein and placebo groups following 1 single dose
Description
measured by the analyze of Insulin in blood
Time Frame
Acute effect after first product intake + chronic effect after 36 days of intake
Title
Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups following 1 single dose
Description
measured by the analyze of free fatty acid concentration (FFA, TG) in blood
Time Frame
Acute effect after first product intake + chronic effect after 36 days of intake
Title
Exploratory outcomes - to evaluate the changes of blood pressure between oleuropein and placebo groups following 1 single dose
Description
measured using automated inflatable cuff
Time Frame
Acute effect after first product intake + chronic effect after 36 days of intake
Title
Exploratory outcomes - to evaluate the changes of anti-inflammatory markers between oleuropein and placebo groups
Description
measured by the analyze of anti-inflammatory markers in blood
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes of Antioxidant markers between oleuropein and placebo groups
Description
measured by the analyze of antioxidant markers in blood
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes in glucose concentration between oleuropein and placebo groups
Description
measured by the analyze glucose in blood
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes of insulin concentration between oleuropein and placebo groups
Description
measured by the analyze of insulin in blood
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups
Description
measured by the analyze of free fatty acid concentration (FFA, TG) in blood
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups
Description
measured with the World Health Organisation quality of life questionnaire (WHOQOL-BREF) (rating 0 for 'not at all' and 5 for 'an extreme amount')
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups
Description
measured with the Profile of Mood States - short-form (POMS-SF) - scale (rating 0 for 'not at all' and 4 for 'extremely')
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups
Description
measured with the Quality of Life (QoL) questionnaires
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes in the fatigue perception and mood state pre/post Biodex measurement between oleuropein and placebo groups
Description
measured with the current mood questionnaire (rating 0 for 'not at all' - 4 for 'extremely')
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes in the fatigue perception and mood state pre/post Biodex measurement between oleuropein and placebo groups
Description
RPE visual analog scale Questionnaire - BORG scale (6 for 'no exertion - 20 for 'maximal exertion'
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes to evaluate the changes in body composition between oleuropein and placebo groups
Description
measure the whole body muscle and fat content using Magnetic resonance imaging (MRI)
Time Frame
Chronic effect (after 29 days of supplementation)
Title
Exploratory outcomes - Whole body respiratory exchange ratio - To evaluate the changes of Whole body respiratory exchange ratio (RER) between oleuropein and placebo groups
Description
measure the oxygen and dioxygen volume using Indirect calorimetry with ventilation hood
Time Frame
Chronic effect (after 36 days of supplementation)
Title
Exploratory outcomes - To evaluate the changes of oleuropein metabolites between oleuropein and placebo groups
Description
measure by analyzing Oleuropein metabolites in blood
Time Frame
Chronic effect (after 36 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators of muscle metabolism between oleuropein and placebo groups
Description
measured by analyzing RNAseq and MS-based proteomics
Time Frame
Chronic effect (after 36 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups
Description
measured using Western Blot
Time Frame
Chronic effect (after 36 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups
Description
measured by analyzing polymerase chain reaction
Time Frame
Chronic effect (after 36 days of supplementation)
Title
Exploratory outcomes - to evaluate the changes in Strength between oleuropein and placebo groups
Description
measured using biodex dynanometer
Time Frame
After 4 weeks of supplementation
Title
Exploratory outcomes to evaluate the changes of strenght between oleuropein
Description
measured using biodex dynanometer
Time Frame
Chronic effect (after 29 days of supplementation)
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
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
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luc van Loon
Organizational Affiliation
Maastricht University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maastricht University Medical Centre +
City
Maastricht
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Oleuropein and Muscle Energy Metabolism
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