A Nutrient Cocktail to Protect Against Physical Inactivity

Study Overview
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Brief Summary
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This experiment consists on a 20-day reduction in daily step in free-living active individuals to induce physical inactivity. This will be used to test the efficacy of the anti-oxidant cocktail we aim to test as a new countermeasure in 2016 during the 60-d bed rest planed by ESA/CNES. The objective of this study is to investigate whether the cocktail of natural antioxidants XXS-2A comprising vitamin E and coupled with omega-3 helps to prevent and / or reduce the glucose intolerance and improve oxidative defenses induced by 20 days of physical inactivity through daily step reduction Although physical inactivity is reported to affect glucose tolerance within days of inactivity, we selected a period of 20 days for the effect of the cocktail to take place and assess secondary molecular mechanisms. The effect of this short period of inactivity on metabolism will moreover be boosted during the last 10 days by taking fructose, a sugar found in abundance in fruits, honey and juices, which is known to quickly trigger metabolic deregulation.

Official Title
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Effects of a Cocktail XXS-2A/Omega-3 on Insulin Sensitivity and Oxidative Stress During a 20-day Period of Physical Inactivity: a Controlled, Randomized Pilot Study on 20 Healthy Men

Conditions
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Metabolic Disturbance, Glucose Intolerance, Physical Inactivity, Glucose Metabolism Disorders, Lipid Metabolism Disorders, Oxidative Stress

Intervention / Treatment
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* Dietary Supplement: XXS-2A + Omega-3 + Vitamin E + Selenium
* Dietary Supplement: control diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects, Aged 20-45 years, No obesity or excessive thinness with BMI (weight Kg / height m2) between 22 and 27, Height (cm) between 158 and 190 cm, Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination): in particular, free from any chronic disease or any acute infectious disease or ENT, neurological, orthopaedic, musculoskeletal and cardiovascular disorders, In the active range of population (10000 to 15000 steps/day) No contraindication to lidocaïne, No allergy to peanuts or soya, Non smokers or smoking less than 5 cigarettes/day, No alcohol, no drug dependence and no medical treatment, Regulations Having given written informed consent prior to any procedure related to the study, Covered by Health Insurance System, Not under any administrative or legal supervision, Not under guardianship or trusteeship. Exclusion Criteria: Any history or presence of clinically relevant cardiovascular, neurological or ENT, any chronic disease; any acute infectious disease, Obesity or excessive thinness, Not in the active range of population (<10000 steps/day), Ongoing medical treatment, Poor tolerance to blood sampling, Having given blood (more than 8ml/kg) in a period of 8 weeks or less before the start of the experiment, Subject with contraindication to lidocaïne, Special food diet, vegetarian or vegan or food supplementation, History of food allergy, especially allergy to peanuts or soya, A significant history of allergy, Positive reaction to any of the following tests: HVA IgM (hepatitis A), HBs antigen (hepatitis B), anti-HVC antibodies (hepatitis C), anti-HIV1+2 antibodies, History or presence of drug or alcohol abuse (alcohol consumption > 40 grams/day). General conditions Subject who, in the judgment of the Investigator, is likely to be non-compliant during the study, or unable to cooperate because of a language problem or poor mental development, Subject in the exclusion period of a previous study according to applicable regulations, Subject who has received more than 4500 Euros within 12 months for being a research subject, Subject who cannot be contacted in case of emergency, Incarcerated persons, Subject under guardianship or trusteeship.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control<br>Intervention: Reduction in daily steps up to 2000-3000 steps per day and no structured physical activity + High dose ingestion of fructose (3g/kg/day) glucose (0,5g/kg/day)in the last 10 days of the protocol No cocktail during the protocol Healthy male volunteers in the active range of population (10000 to 15000 steps per day) aged 20-45 years, 22 BMI 27 158 cm height 190 cm, Certified as healthy by a comprehensive clinical assessment. | Dietary Supplement: control diet<br>* habitual diet to be followed<br>|
| Experimental: Cocktail intervention<br>Intervention: Reduction in daily steps up to 2000-3000 steps per day and no structured physical activity + High dose ingestion of fructose (3g/kg/day) glucose (0,5g/kg/day)in the last 10 days of the protocol + Micronutrient cocktail supplementation with 560,7 mg/ day of polyphenols (3 pills/day), 2,1 g/day of omega-3 fatty-acids (3 pills/day), 168 mg/day of vitamin E and 80µg/day of selenium (1 pill/day) Healthy male volunteers in the active range of population (10000 to 15000 steps per day) aged 20-45 years, 22 BMI 27 158 cm height 190 cm, Certified as healthy by a comprehensive clinical assessment. | Dietary Supplement: XXS-2A + Omega-3 + Vitamin E + Selenium<br>* Micronutrient cocktail supplementation with 560,7 mg/ day of polyphenols (3 pills/day), 2,1 g/day of omega-3 fatty-acids (3 pills/day), 168 mg/day of vitamin E and 80µg/day of selenium (1 pill/day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lipid oxidation | change in lipid oxidation as measured by indirect calorimetry during a 4h-OGTT | 20 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glucose concentration | Change in plasma glucose concentration during a 4h-OGTT | 20 days | 
| Change in insulin concentration | Change in plasma insulin concentration during a 4h-OGTT | 20 days | 
| Change in NEFA | Change in fasting plasma NEFA | 20 days | 
| Change in triglycerides | Change in fasting plasma triglycerides | 20 days | 
| de novo lipogenesis | incorporation of labelled fructose in VLDL-TG | 20 days | 
| Change in fructose oxidation | Change in 13C recovery in breath samples from ingested 1-13C fructose | 20 days | 
| Change in oxidative stress | Change in fasting reduced and oxidized glutathione | 20 days | 
| Change in fat-free mass | Change in fat-free mass as measured by DXA | 20 days | 
| muscle pathways involved in intertwined protein synthesis / insulin sensitivity | western blots with Vastes lateralis samples obtained from muscle biopsy | 4h for each day of test. 12h for all the protocol | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolism, Lipid oxidation, micronutrient cocktail supplementation, physical inactivity, glucose intolerance, oxidative stress