Nutritional Intervention With Table Olives in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
Olives and olive oil are typical components of the Mediterranean diet being part of its cultural and gastronomic heritage. Since ancient times, olives have been used either for both, oil extraction or whole fruit consumption as table olives. Olive oil stands out from both the nutritional and the health point of view. However, the effect of table olives consumption remains almost unknown. The beneficial properties of olive oil have been initially ascribed to the high concentration of oleic acid. Nowadays, these positive effects have been attributed also to minor compounds such as polyphenols or pentacyclic triterpenes. Table olives contain a higher amount of both polyphenols and pentacyclic triterpenes than their oil, with the same healthy fatty acid profile. Therefore, the present intervention aims at investigating the pharmacokinetic of polyphenols and pentacyclic triterpenes after a single olive intake as well as the assessment of the effect of the consumption of olives during 30 days on the overall health status playing particular attention to the anti-inflammatory, antioxidant and cardiovascular biomarkers.

Official Title
-----------------
Table Olives Nutritional Intervention: Pharmacokinetics of Polyphenols and Pentacyclic Triterpenes and Assessment of Antioxidant, Cardiovascular and Anti-inflammatory Biomarkers

Conditions
-----------------
Healthy, Biological Availability, Nutritional Intervention, Functional Food, Nutrition Physiology

Intervention / Treatment
-----------------
* Other: Table Olives
* Other: Table Olives
* Other: Table Olives


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body Mass Index between 19 and 30 kg/m2. Healthy on the basis of physical examination and routine biochemical and hematological laboratory determinations. Free acceptance to participate in the study by obtains signed informed consent. Exclusion Criteria: Smoking. Alcohol or drug abuse. Heavy consumer of stimulating beverages (>5 coffees, teas, chocolate or cola drinks per day) and grapefruit juice. Background of allergy, idiosyncrasy or hypersensitivity to drugs. Intake of any medication within 2 weeks prior taking the study intervention (except for use of paracetamol in short-term symptomatic treatments), including over-the-counter products (including natural food supplements, vitamins and medicinal plants products), or any enzymatic inductor or inhibitor within 3 months before the drug administration. Positive serology for hepatitis B, C or HIV. Background or clinical evidence of cardiovascular, respiratory, renal, hepatic, endocrine, gastrointestinal, hematological or neurological disease or other chronic diseases. Having undergone major surgery during the previous 6 months. Pregnancy or lactation status (if applied). Participation in another clinical trial during the 3 months preceding the drug administration. Donation of blood during the 4 weeks preceding the drug administration. Acute illness four weeks before drug administration.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study involve two stages, the first one corresponding to the pharmacokinetic study of the single administration of table olives in healthy male volunteers and the second one corresponding to the study of a nutritional intervention with 30 table olives during 30 days.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 60 Arbequina Table Olives<br>Pharmacokinetics Study | Other: Table Olives<br>* At early morning (08:00 h e.g.) and after 10 hours of fasting conditions, the olives of the Arbequina variety will be administered to each subject. The 60 olives will be weighted before the ingestion and the remaining stones will be subsequently weighted to keep a record of the amount of olive pulp that has been consumed. The subjects will have a period of 5 minutes to ingest 60 olives with 240 mL of water. Blood samples will be collected from 1 hour prior to administration until 24 hours after dosing. Urine samples will also be collected and blood pressure will be measured.<br>|
| Experimental: 120 Arbequina Table Olives<br>Pharmacokinetics Study | Other: Table Olives<br>* At early morning (08:00 h e.g.) and after 10 hours of fasting conditions, the olives of the Arbequina variety will be administered to each subject. The 120 olives will be weighted before the ingestion and the remaining stones will be subsequently weighted to keep a record of the amount of olive pulp that has been consumed. The subjects will have a period of 10 minutes to ingest 120 olives with 240 mL of water. Blood samples will be collected from 1 hour prior to administration until 24 hours after dosing. Urine samples will also be collected and blood pressure will be measured.<br>|
| Experimental: 60 Table Olives<br>Table Olives Nutritional Intervention | Other: Table Olives<br>* All the subjects will perform two experimental sessions of 30 days with 15 days of washout periods within experimental periods. In one experimental session subjects will ingest table olives and in the other session they will act as their own controls following their normal dietary habits. During all the experiment participants will avoid the consumption of products rich in phenolic and triterpenic compounds. Subjects will include the dose of 60 table olives within their normal dietary habits. Consequently, the olives will be consumed two times daily within each main meal; 30 olives before lunch and 30 olives before dinner. Blood samples will be collected at baseline and 15 and 30 days of each experimental session. Tolerability variables and blood pressure will also be measured.<br>|
| No Intervention: Control<br>Control of Table Olives Nutritional Intervention | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 1: Maximum plasma concentration (Cmax) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Concentration at the end of the dosing interval (Ct) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Time until Cmax is reached (Tmax) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Area under the curve from administration to last observed concentration at time (AUC (0-t) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: AUC extrapolated to infinite time (AUC (0-∞) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Percentage of AUC extrapolated (AUC%) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Terminal elimination rate constant (Kel) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Plasma concentration half-life (t ½) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Volume of distribution (Vd/ F) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Clearance (Cl/F) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Peak trough fluctuation over one dosing interval at steady state (PTF) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Cmax dose normalized (Cmax/Dose) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: AUC (0-t) dose normalized (AUC (0-t)/Dose) | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Urine polyphenols concentration | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 1: Urine triterpenes concentration | 24 hour dosing period; 2 dosing periods each separated by 7 days washout | 24 hours | 
| Stage 2: Plasma polyphenols concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Plasma triterpenes concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Urine polyphenols concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Urine triterpenes concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Malondialdehyde concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Catalase concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Glutathione peroxidase concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Superoxide dismutase concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: F2A isoprostane concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: 8 isoprostane concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Oxidized low-density lipoprotein concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: C-Reactive Protein concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Lipoprotein-associated phospholipase A2 concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Apolipoprotein A1 concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Apolipoprotein B100 concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Tumor necrosis factor alpha concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Interleukin 6 concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Interleukin 1 concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 1 and 2: Number of participants with treatment-related adverse events | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 1 and 2: Systolic and diastolic blood pressure | Stage 1: 24 hours, Stage 2: 30 days | Stage 1: 24 hour dosing period; 2 dosing periods each separated by 7 days washout, Stage 2: 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 1 and 2: Heart rate | Stage 1: 24 hours, Stage 2: 30 days | Stage 1: 24 hour dosing period; 2 dosing periods each separated by 7 days washout, Stage 2: 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 1 and 2: Respiratory rate | Stage 1: 24 hours, Stage 2: 30 days | Stage 1: 24 hour dosing period; 2 dosing periods each separated by 7 days washout, Stage 2: 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Body weight | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: High-density lipoprotein cholesterol concentration (HDL-C) | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Low-density lipoprotein cholesterol concentration (LDL-C) | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Very low-density lipoprotein cholesterol concentration (VLDL-C) | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Triglyceride concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Total cholesterol concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Sodium concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Glucose concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Urea concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Creatinine concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Aspartate aminotransferase concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Alanine aminotransferase concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Alkaline phosphatase concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 
| Stage 2: Total proteins concentration | 30 days | 30 days dosing period or 30 days as control group separated by 15 days washout | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polyphenols, Triterpenes, Olea europaea, Table Olives, Pharmacokinetics, Functional Food, Antioxidant, Cardiovascular Disease, Anti-inflammatory