Oleuropein and Muscle Energy Metabolism

Muscular Fatigue Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05217433
• Other study ID #: 20.22.NRC
• Status: Completed
• Phase: N/A
• Start date: November 4, 2021
• Est. completion date: March 10, 2023

Study information

• Verified date: March 2023
• Source: Société des Produits Nestlé (SPN)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 10, 2023
• Est. primary completion date: March 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 50 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatigue
• Muscular Fatigue

Intervention

Other:
• Olive leaf extract
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
The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Centre +	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Société des Produits Nestlé (SPN)	Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose	measured by western blotting	Chronic effect after 36 days of intake
Primary	Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose	measured by biochemical assay analysis	Acute effect after first product intake + chronic effect after 36 days of intake
Primary	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.	Acute effect after first product intake + chronic effect after 36 days of intake
Primary	Exploratory outcomes- to evaluate the changes of fatigue between oleuropein and placebo groups following 1 single dose	measured using Biodex dynamometer	After 4 weeks of supplementation
Primary	Exploratory outcomes - to evaluate the changes of fatigue between oleuropein and placebo groups	measured using Biodex dynamometer	Chronic effect (after 29 days of supplementation)
Primary	Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups	measured by western blotting	Chronic effect (after 36 days of supplementation)
Primary	Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups	measured by biochemical assay analysis	Chronic effect (after 36 days of supplementation)
Primary	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.	Chronic effect (after 36 days of supplementation)
Secondary	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	Acute effect after first product intake+ chronic effect after 36 days of intake
Secondary	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	Acute effect after first product intake + chronic effect after 36 days of intake
Secondary	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	Acute effect after first product intake + chronic effect after 36 days of intake
Secondary	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	Acute effect after first product intake + chronic effect after 36 days of intake
Secondary	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	Acute effect after first product intake + chronic effect after 36 days of intake
Secondary	Exploratory outcomes - to evaluate the changes of blood pressure between oleuropein and placebo groups following 1 single dose	measured using automated inflatable cuff	Acute effect after first product intake + chronic effect after 36 days of intake
Secondary	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	Chronic effect (after 29 days of supplementation)
Secondary	Exploratory outcomes - to evaluate the changes of Antioxidant markers between oleuropein and placebo groups	measured by the analyze of antioxidant markers in blood	Chronic effect (after 29 days of supplementation)
Secondary	Exploratory outcomes - to evaluate the changes in glucose concentration between oleuropein and placebo groups	measured by the analyze glucose in blood	Chronic effect (after 29 days of supplementation)
Secondary	Exploratory outcomes - to evaluate the changes of insulin concentration between oleuropein and placebo groups	measured by the analyze of insulin in blood	Chronic effect (after 29 days of supplementation)
Secondary	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	Chronic effect (after 29 days of supplementation)
Secondary	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')	Chronic effect (after 29 days of supplementation)
Secondary	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')	Chronic effect (after 29 days of supplementation)
Secondary	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	Chronic effect (after 29 days of supplementation)
Secondary	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')	Chronic effect (after 29 days of supplementation)
Secondary	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'	Chronic effect (after 29 days of supplementation)
Secondary	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)	Chronic effect (after 29 days of supplementation)
Secondary	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	Chronic effect (after 36 days of supplementation)
Secondary	Exploratory outcomes - To evaluate the changes of oleuropein metabolites between oleuropein and placebo groups	measure by analyzing Oleuropein metabolites in blood	Chronic effect (after 36 days of supplementation)
Secondary	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	Chronic effect (after 36 days of supplementation)
Secondary	Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups	measured using Western Blot	Chronic effect (after 36 days of supplementation)
Secondary	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	Chronic effect (after 36 days of supplementation)
Secondary	Exploratory outcomes - to evaluate the changes in Strength between oleuropein and placebo groups	measured using biodex dynanometer	After 4 weeks of supplementation
Secondary	Exploratory outcomes to evaluate the changes of strenght between oleuropein	measured using biodex dynanometer	Chronic effect (after 29 days of supplementation)