Dietary Strategy to Tackle Sarcopenia in Early Elderly Subjects (FOOP-Sarc)

Study Overview
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Brief Summary
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The main objective of the present study is to add knowledge of the potential health effects and mechanism of action by a dietary strategy based on a VOO rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil) alone or combination with prebiotic supplementation based on fructooligosaccharides (FOS) and inulin to tackle sarcopenia by improving skeletal muscle mass and function and CVD risk factors in early elderly (60-80 years) home-dwelling sarcopenic subjects. The specific objectives: To determine the compliance food intake biomarkers of VOO in 24h urine samples and prebiotic intake in faecal samples. To evaluate the effect of the NFOC-diet supplemented by VOO rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil) alone or in combination with prebiotic supplementation (FOS and inulin) on the improvement of muscle mass, muscle performance, gait performance, cardiovascular disease risk factors (inflammation, oxidation and endothelial function), and gut microbiota, in sarcopenic young-elderly subjects. To assess the mechanisms of action of the NFOC-diet supplemented by VOO rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil) alone or in combination with prebiotic supplementation (FOS and inulin) involved in the development of sarcopenia and cardiovascular disease in vivo and in vitro cellular models. To determine if the effects achieved after the intervention (12 weeks of intervention) will be sustained 12 weeks after the FOOP-Sarc intervention cessation (12 weeks of intervention + 12 weeks of follow-up), by assessing the sarcopenia and CVD risk factors in sarcopenic early elderly subjects. To co-create nutritional and physical activity recommendations of FOOP-Sarc study based on sarcopenia improvement by a sample of volunteers of the FOOP-Sarc study, and to assess the adherence and the effectivity of the recommendations, in comparison to standard recommendations created by researchers, the satisfaction and engagement experience in a co-creation process, and the usability of recommendations.

Detailed Description
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The prebiotic supplementation about FOS and inulin was related to gut microbiota transformation an increase in handgrip strength and a reduction of exhaustion in older adults over 65 years old. In the role of a nutritional intervention for the treatment of sarcopenia, an adequate intake of protein, especially leucine, vitamin D and antioxidant nutrients are recommended. In particular, dietary protein is a key anabolic stimulus for muscle protein synthesis. Moreover, food such as, virgin olive oil (VOO) can be involved in sarcopenia, by modulation of pro-inflammatory cytokines and could attenuate sarcopenic symptomology. On the other hand, physical activity (PA) is an important aspect to avoid loss of muscle mass, for this reason, in sarcopenic subjects it is recommended to spend 150 min/week of moderate to vigorous physical activity. A total of 135 home-dwelling early elderly volunteers will be included in the intervention (45 in each arm of the intervention). The total duration of the study will be 24 weeks (12-week period of dietary-lifestyle treatment and a 12-week period of follow-up after intervention cessation). Additionally, a total of 36 home-dwelling early elderly volunteers will be included in the co-creation process. Specifically, 12 home-dwelling early elderly volunteers will participate in the co-ideation and co-design steps. Additionally, 24 home-dwelling early elderly volunteers will participate in the co-implementation and comparison of recommendations (12 in each arm of intervention). The sample of volunteers that will co-implement will be randomized and different from the sample of volunteers that will co-ideate and co-design the recommendations. The co-evaluation step will include all 36 volunteers from the different steps of the co-creation process. During the preliminary co-creation phase, there will be 5 visits over 5 weeks. The study visits will be the following: screening visit (V0): to check inclusion/exclusion criteria and, in case of satisfying the inclusion criteria; visits during the intervention (V1, V2, V3); and final study visit (V4). The volunteers that will co-ideate and co-design the recommendations will carry out only the V0, V1, V2, and V4. Instead, the co-implement volunteers will carry out only the visits V0, V3, and V4. Additionally, during the FOOP-Sarc study, there will be 7 visits in total (6 visits during the intervention period and 1 follow-up visit). Of these visits, 4 will be face-to-face and 3 by telephone. The study visits will be the following: screening visit (V0, face-to-face): to check inclusion/exclusion criteria and, in case of satisfying the inclusion criteria; basal visit (V1); visits during the intervention (V2, telephone; V3, telephone; V4, telephone); final study visit (V5, face-to-face); and follow-up visit (V6, face-to-face): follow-up visit 12-week after intervention cessation. In visits V0, V1, V5, and V6 volunteers must present themselves in fasting conditions of 8 hours to obtain blood. In visits V1, V5, and V6 volunteers must bring urine and feaces samples.

Official Title
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Foods Such as Virgin Olive Oil Rich in Phenolic Compounds, and Prebiotic Supplementation: Dietary Strategy to Tackle Sarcopenia in Early Elderly Subjects (FOOP-Sarc)

Conditions
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Sarcopenia

Intervention / Treatment
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* Dietary Supplement: Refined olive oil (38.6 mg hydroxytyrosol and tyrosol/kg oil)
* Dietary Supplement: Virgin olive oil rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil)
* Dietary Supplement: Maltodextrin
* Dietary Supplement: Prebiotic (FOS and inulin)
* Other: Nutritional and physical activity recommendations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women with and age equal to or greater than 60 years and until 80 years. Written informed consent provided before the initial visit. Sarcopenia assessment: low muscle strength based on grip dynamometry, kg (men <30 kg; women <20 kg) or low skeletal muscle mass index (SMI) based on bioimpedance analysis (BIA), kg/m2 (men <8,87 kg/m2; women <6,42 kg/m2) or low physical performance or physical function based on 4m gait speed, m/s (≤0,8 m/s) Exclusion Criteria: Type 2 or insulin-dependent diabetes diagnosed. Anemia (hemoglobin ≤13 g/dL in men and ≤12 g/dL in women). Intestinal malabsorption diseases. Fructose and/or sucrose intolerance. Malnutrition (assessed by albumin <3,5 g/dl). Renal diseases. Chronic alcoholism. Current or past participation in a clinical trial or consumption of a research product in the 30 days prior to inclusion in the study. Institutionalized elderly. Failure to follow the study guidelines.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, controlled, parallel and double-blind intervention study. The total duration of the study will be 24 weeks (12-weeks of intervention and 12-weeks of follow-up). The study will have three arms of intervention. The intervention products will be prebiotic supplement based on FOS and inulin or virgin olive oil rich in phenolic compounds with 156 mg hydroxytyrosol and tyrosol/kg oil. The placebo will be refined olive oil (38.6 mg hydroxytyrosol and tyrosol/kg oil) or maltodextrin. Both with the same format and appearance, to ensure the double-blind intervention. All the volunteers will receive NFOC-diet and physical activity recommendations co-created during the co-creation study. The nutritional recommendations are based on DASH diet and foods rich in protein (in particular, leucine), vitamin D, polyunsaturated acids, phosphorus and iron. The physical activity recommendations are 150 min/week of physical activity, with at least two sessions focused on motor strength.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group (Group A)<br>Refined olive oil (38.6 mg hydroxytyrosol and tyrosol/kg oil), maltodextrin, and nutritional and physical activity recommendations | Dietary Supplement: Refined olive oil (38.6 mg hydroxytyrosol and tyrosol/kg oil)<br>* The dosage will be 30 ml/day of refined olive oil (38.6 mg hydroxytyrosol and tyrosol/kg oil) used as a dressing (without heat).<br>Dietary Supplement: Maltodextrin<br>* The dosage will be 7,5 g/day of maltodextrin.<br>Other: Nutritional and physical activity recommendations<br>* The nutritional recommendations are based on DASH diet and foods rich in protein (in particular, leucine) and vitamin D, polyunsaturated acids, phosphorus and iron. The physical activity recommendations are 150 min/week of physical activity, with at least two sessions dedicated to the development of motor strength.<br>|
| Experimental: Intervention group (Group B)<br>Virgin olive oil rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil), maltodextrin, and nutritional and physical activity recommendations | Dietary Supplement: Virgin olive oil rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil)<br>* The dosage will be 30 ml/day of virgin olive oil rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil) used as a dressing (without heat).<br>Dietary Supplement: Maltodextrin<br>* The dosage will be 7,5 g/day of maltodextrin.<br>Other: Nutritional and physical activity recommendations<br>* The nutritional recommendations are based on DASH diet and foods rich in protein (in particular, leucine) and vitamin D, polyunsaturated acids, phosphorus and iron. The physical activity recommendations are 150 min/week of physical activity, with at least two sessions dedicated to the development of motor strength.<br>|
| Experimental: Intervention group (Group C)<br>Virgin olive oil rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil), prebiotic supplementation (FOS and inulin), and nutritional and physical activity recommendations | Dietary Supplement: Virgin olive oil rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil)<br>* The dosage will be 30 ml/day of virgin olive oil rich in phenolic compounds (156 mg hydroxytyrosol and tyrosol/kg oil) used as a dressing (without heat).<br>Dietary Supplement: Prebiotic (FOS and inulin)<br>* The dosage will be 7,5 g/day of prebiotic supplement (FOS and inulin).<br>Other: Nutritional and physical activity recommendations<br>* The nutritional recommendations are based on DASH diet and foods rich in protein (in particular, leucine) and vitamin D, polyunsaturated acids, phosphorus and iron. The physical activity recommendations are 150 min/week of physical activity, with at least two sessions dedicated to the development of motor strength.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle mass | The change in muscle mass will be assessed by Magnetic Nuclear Resonance (MNR) measured lumbar 3rd vertebra. | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body-weight | Measured with calibrated scale in kg | Visit 0 (week -1), visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Height | Measured with wall-mounted stadiometer in cm | Visit 0 (week -1), visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Body Mass Index | Calculated by weight (kg) divided to height (m2) | Visit 0 (week -1), visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Body weight composition | Measured by bioimpedance (Tanita SC 330-S) | Visit 0 (week -1), visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Waist circumference | Steel measuring tape at the umbilicus in cm. | Visit 0 (week -1), visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Sarcopenia assessment_skeletal muscle strength | grip strength, kg: Handheld dynamometer and the maximum value from either hand will be analyzed (Jamar dynamometer; Sammons Preston Rolyan, Bolingbrook, IL) | Visit 0 (week -1), visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Sarcopenia assessment_muscle mass | Muscle mass, wasting and turnover: assessed by Magnetic Nuclear Resonance (MNR) measured lumbar 3rd vertebra | Visit 0 (week -1), visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Sarcopenia assessment_muscle physical performance | Gait speed, m/s: length of the walking course divided by the time | Visit 0 (week -1), visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Compliance of physical activity recommendations | IPAQ-E Spanish version | Visit 1 (week 0), visit 2 (week 2), visit 3 (week 4), visit 4 (week 6) visit 5 (week 8), visit 6 (week 10), visit 7 (week 12), visit 8 (week 24) | 
| Compliance of the dietary recommendations | Dietary record: 3-day dietary record | Visit 1 (week 0), visit 2 (week 2), visit 3 (week 4), visit 4 (week 6) visit 5 (week 8), visit 6 (week 10), visit 7 (week 12), visit 8 (week 24) | 
| Dietary compliance markers | Folin-Ciocalteau method adjusted by creatinine values, measured in 24h urine samples | Visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Specific phenolic compounds_dietary compliance markers | Specific phenolic compounds and metabolites assessed by Ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS) in urine samples | Visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Phenolic metabolites_dietary compliance markers | Phenolic metabolites by UPLC-MS/MS in plasma | Visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Sarcopenia and Quality of life | SarQoL® test assessed by quality of life test adapted to sarcopenic subjects. It is scored from 0 to 100, where higher values indicate better quality of life. | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Fasting blood glucose (FBG) | by standardized methods in an automated analyzer (Beckman Coulter-Synchron, Galway, Ireland) in (mmol/L) | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Insulin | by standardized methods in an automated analyzer (Beckman Coulter-Synchron, Galway, Ireland) in (IU/mL) | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Homeostasis model assessment index (HOMA index) | Calculated by fasting insulin (μUI/mL) x fasting glucose (mmol/L) / 22,5 | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Lipid profile | Total cholesterol (TC), high density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc) and Total triglycerides (TG) in mmol/L by standardized enzymatic automated methods in an autoanalyzer (Beckman Coulter-Synchron, Galway, Ireland) | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Apolipoproteins | Apolipoprotein A1 (ApoA1) and apolipoprotein B100 (ApoB100) in mg/dL by standardized enzymatic automated methods in an autoanalyzer (Beckman Coulter-Synchron, Galway, Ireland) | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Apolipoproteins ratio | Calculated by ApoA1 divided to ApoB100 | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Vascular parameters_endothelial function | Ischemic reactive hyperemia (IRH) with Laser-Doppler Linear Periflux 5000 (Perimed AB, Järfälla, Stockholm, Sweden) | Visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Vascular parameters_blood pressure | Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) in mm Hg by automatic sphygmomanometer (OMRON HEM-907; Peroxfarma, Barcelona, Spain). | Visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Vascular parameters_pulse pressure | Calculated by SBP - DBP | Visit 1 (week 0), visit 3 (week 4), visit 5 (week 8), visit 7 (week 12), visit 8 (week 24) | 
| Endothelin | Endothelin in pg/mL assessed by Commercial ELISA | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Endothelial dysfunction markers | E-selectin (CD62E), P-selectin (CD62P), Intercellular Cell Adhesion Molecule 1 (ICAM-1 (CD54)) and Vascular Cell Adhesion Molecule 1 (VCAM-1 (CD106) assessed by multi-analyte ELISArray kits. | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Oxidative biomarkers_Oxidized LDL | Oxidized LDL (oxLDL) assessed by commercial ELISA. | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Oxidative biomarkers_Superoxide Dismutase | Superoxide Dismutase (SOD) in U/g Hb assessed by enzymatic assay | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Oxidative biomarkers_Glutathione peroxidase | Glutathione peroxidase (GSHPx) in nmol/mL assessed by enzymatic assay | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Inflammation biomarkers_High sensitivity C-reactive protein | High sensitivity C-reactive protein (hsCRP) in mg/L assessed by Immunoturbidimetry on an autoanalyzer (Roche Diagnostics Systems, Madrid, Spain) | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Inflammation biomarkers_interleukine-6 | Interleukine-6 (IL-6) in pg/mL assessed by Immunoturbidimetry on an autoanalyzer (Roche Diagnostics Systems, Madrid, Spain) | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Inflammation biomarkers_uric acid | Uric acid in mg/dL is assessed by Immunoturbidimetry on an autoanalyzer (Roche Diagnostics Systems, Madrid, Spain) | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Inflammation biomarkers_tumour necrosis factor-α | Tumour necrosis factor-α (TNF-α) in pg/mL is assessed by commercial ELISA kit. | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Renal function_creatinine | Creatinine in mg/dL is assessed by standardized methods in a Cobas Mira Plus autoanalyzer (Roche Diagnostics Systems, Madrid, Spain) in 24 h urine samples | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Renal function_glomerular filtration rate | Glomerular filtration rate (GFR) in mL/minutes/1.73m2 is assessed by equation Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Endocrine system | Testosterone (pg/mL) and growth hormone (GH) (pg/mL)) assessed by in a Cobas Mira Plus autoanalyzer (Roche Diagnostics Systems, Madrid, Spain) | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Proteome profiling | Whole proteome assessed by nano Liquid chromatography-mass spectrometry (nLC-MS) according to our previous work. | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Gut microbiota_phyla composition and functionality | Phyla composition and functionality assessed by whole genomic content sequencing. Illumina platform will be used to obtain the metagenomics and metatranscriptomics of each sample following previous protocols developed in Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO-Salud Pública (Valencia)). | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 
| Gut microbiota_short chain fatty acids | Short chain fatty acids (SCFA): bile acids, sterols, buthyrate, and branched chain amino acids and sterols assessed by gas chromatography (GC) | Visit 1 (week 0), visit 7 (week 12), visit 8 (week 24) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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early elderly, olive oil, prebiotic supplementation, muscle mass, muscle strength, physical performance