Clinical trial NCT05217433: 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
Overall status: COMPLETED
Phase: NA
Conditions: Muscular Fatigue
Keywords: Skeletal muscle energy and fatigue
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
Collaborators: name: Maastricht University Medical Center
First posted: 2022-02-01
Enrollment: 40
Sex: MALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a single-centre, double-blind, placebo controlled, randomised 2-arms parallel group study.
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

1. Male
2. 50 to 70 years old
3. BMI 18.5-29.9 kg/m2
4. Healthy as per medical history and investigator's/ physician's judgement
5. Having given informed consent

Exclusion Criteria:

1. Allergy/intolerance to the study product
2. \>5% body mass change in the previous 3 months
3. HbA1c ≥ 6.5%
4. Blood pressure \>140/90 mmHg
5. Participating in a structured (progressive) exercise program
6. Smoking
7. Diagnosed acute or chronic medical conditions that, in the opinion of the investigator, could impact study outcomes
8. Diagnosed musculoskeletal disorders
9. Chronic use of gastric acid suppressing medication
10. 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
11. 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
12. Overly imbalanced or restrictive diet (e.g. hyperproteic, vegan, ketogenic, etc.)
13. Subjects not willing and/or not able to comply with scheduled visits and the requirements of the study protocol
14. Any implants that would be a contra-indication for performing an MRI scan.
15. Participation in another study at the same time
16. Blood donation in the past 2 months

Primary outcomes:
measure: Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose
timeFrame: Chronic effect after 36 days of intake
measure: Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose
timeFrame: Acute effect after first product intake + chronic effect after 36 days of intake
measure: Exploratory outcomes - to evaluate the changes Mitocondrial respiration between oleuropein and placebo groups following 1 single dose
timeFrame: Acute effect after first product intake + chronic effect after 36 days of intake
measure: Exploratory outcomes- to evaluate the changes of fatigue between oleuropein and placebo groups following 1 single dose
timeFrame: After 4 weeks of supplementation
measure: Exploratory outcomes - to evaluate the changes of fatigue between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
timeFrame: Chronic effect (after 36 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
timeFrame: Chronic effect (after 36 days of supplementation)
measure: Exploratory outcomes - To evaluate the changes of Mitochondrial respiration between oleuropein and placebo groups
timeFrame: Chronic effect (after 36 days of supplementation)
Secondary outcomes:
measure: Exploratory outcomes - to evaluate the changes of whole body respiratory exchange ratio (RER) between oleuropein and placebo groups following 1 single dose
timeFrame: Acute effect after first product intake+ chronic effect after 36 days of intake
measure: Exploratory outcomes - to evaluate the changes of oleuropein metabolites between oleuropein and placebo groups following 1 single dose
timeFrame: Acute effect after first product intake + chronic effect after 36 days of intake
measure: Exploratory outcomes - to evaluate the changes of glucose concentration between oleuropein and placebo groups following 1 single dose
timeFrame: Acute effect after first product intake + chronic effect after 36 days of intake
measure: Exploratory outcomes - to evaluate the changes Blood glucose, insulin, free fatty acid concentrations -between oleuropein and placebo groups following 1 single dose
timeFrame: Acute effect after first product intake + chronic effect after 36 days of intake
measure: Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups following 1 single dose
timeFrame: Acute effect after first product intake + chronic effect after 36 days of intake
measure: Exploratory outcomes - to evaluate the changes of blood pressure between oleuropein and placebo groups following 1 single dose
timeFrame: Acute effect after first product intake + chronic effect after 36 days of intake
measure: Exploratory outcomes - to evaluate the changes of anti-inflammatory markers between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes of Antioxidant markers between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes in glucose concentration between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes of insulin concentration between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes in the fatigue perception and mood state pre/post Biodex measurement between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes in the fatigue perception and mood state pre/post Biodex measurement between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes to evaluate the changes in body composition between oleuropein and placebo groups
timeFrame: Chronic effect (after 29 days of supplementation)
measure: Exploratory outcomes - Whole body respiratory exchange ratio - To evaluate the changes of Whole body respiratory exchange ratio (RER) between oleuropein and placebo groups
timeFrame: Chronic effect (after 36 days of supplementation)
measure: Exploratory outcomes - To evaluate the changes of oleuropein metabolites between oleuropein and placebo groups
timeFrame: Chronic effect (after 36 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators of muscle metabolism between oleuropein and placebo groups
timeFrame: Chronic effect (after 36 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups
timeFrame: Chronic effect (after 36 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups
timeFrame: Chronic effect (after 36 days of supplementation)
measure: Exploratory outcomes - to evaluate the changes in Strength between oleuropein and placebo groups
timeFrame: After 4 weeks of supplementation
measure: Exploratory outcomes to evaluate the changes of strenght between oleuropein
timeFrame: Chronic effect (after 29 days of supplementation)
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre +
Study officials:
affiliation: Maastricht University Medical Center
name: Luc van Loon
role: PRINCIPAL_INVESTIGATOR
References: