A Randomized, Double-blind, Placebo Controlled Study to Investigate the Efficacy of Oleuropein on Skeletal Muscle Energy Metabolism and Fatigue in Humans
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
This is a single-centre, double-blind, placebo controlled, randomised 2-arms parallel group study.
入排标准
- 年龄范围
- 50 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Control arm
The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.
干预措施: Placebo (Other)
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).
干预措施: Olive leaf extract (Other)
结局指标
主要结局
Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups
时间窗: Chronic effect (after 36 days of supplementation)
measured by western blotting
Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose
时间窗: Acute effect after first product intake + chronic effect after 36 days of intake
measured by biochemical assay analysis
Exploratory outcomes- to evaluate the changes of fatigue between oleuropein and placebo groups following 1 single dose
时间窗: After 4 weeks of supplementation
measured using Biodex dynamometer
Exploratory outcomes - to evaluate the changes of fatigue between oleuropein and placebo groups
时间窗: Chronic effect (after 29 days of supplementation)
measured using Biodex dynamometer
Exploratory outcomes - to evaluate the changes Mitocondrial respiration between oleuropein and placebo groups following 1 single dose
时间窗: Acute effect after first product intake + chronic effect after 36 days of intake
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 Mitochondrial respiration between oleuropein and placebo groups
时间窗: Chronic effect (after 36 days of supplementation)
measured the rates of oxygen consumption (respiration or JO2) using Oroboros Oxygraph 2K systems with physiological ADP concentrations using permeabilized muscle fibres.
Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose
时间窗: Chronic effect after 36 days of intake
measured by western blotting
次要结局
- Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups(Chronic effect (after 29 days of supplementation))
- Exploratory outcomes - to evaluate the changes in Strength between oleuropein and placebo groups(After 4 weeks of supplementation)
- Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups(Chronic effect (after 36 days of supplementation))
- Exploratory outcomes - to evaluate the changes in the fatigue perception and mood state pre/post Biodex measurement between oleuropein and placebo groups(Chronic effect (after 29 days of supplementation))
- Exploratory outcomes - to evaluate the changes of glucose concentration between oleuropein and placebo groups following 1 single dose(Acute effect after first product intake + chronic effect after 36 days of intake)
- Exploratory outcomes - to evaluate the changes of oleuropein metabolites between oleuropein and placebo groups following 1 single dose(Acute effect after first product intake + chronic effect after 36 days of intake)
- Exploratory outcomes - to evaluate the changes in glucose concentration between oleuropein and placebo groups(Chronic effect (after 29 days of supplementation))
- Exploratory outcomes - to evaluate the changes Blood glucose, insulin, free fatty acid concentrations -between oleuropein and placebo groups following 1 single dose(Acute effect after first product intake + chronic effect after 36 days of intake)
- Exploratory outcomes - to evaluate the changes of blood pressure between oleuropein and placebo groups following 1 single dose(Acute effect after first product intake + chronic effect after 36 days of intake)
- Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups following 1 single dose(Acute effect after first product intake + chronic effect after 36 days of intake)
- Exploratory outcomes - to evaluate the changes of anti-inflammatory markers between oleuropein and placebo groups(Chronic effect (after 29 days of supplementation))
- Exploratory outcomes - to evaluate the changes of Antioxidant markers between oleuropein and placebo groups(Chronic effect (after 29 days of supplementation))
- Exploratory outcomes - to evaluate the changes of insulin concentration between oleuropein and placebo groups(Chronic effect (after 29 days of supplementation))
- Exploratory outcomes to evaluate the changes in body composition between oleuropein and placebo groups(Chronic effect (after 29 days of supplementation))
- Exploratory outcomes - to evaluate the changes of whole body respiratory exchange ratio (RER) between oleuropein and placebo groups following 1 single dose(Acute effect after first product intake+ chronic effect after 36 days of intake)
- Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups(Chronic effect (after 29 days of supplementation))
- Exploratory outcomes - Whole body respiratory exchange ratio - To evaluate the changes of Whole body respiratory exchange ratio (RER) between oleuropein and placebo groups(Chronic effect (after 36 days of supplementation))
- Exploratory outcomes - To evaluate the changes of oleuropein metabolites between oleuropein and placebo groups(Chronic effect (after 36 days of supplementation))
- Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators of muscle metabolism between oleuropein and placebo groups(Chronic effect (after 36 days of supplementation))
- Exploratory outcomes to evaluate the changes of strenght between oleuropein(Chronic effect (after 29 days of supplementation))