BIOLIVA: Nutritional Intervention With Table Olives in Healthy Volunteers

Sponsor

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau (Other)

Overall Status

Completed

CT.gov ID

NCT03886597

Collaborator

Ministerio de Economía y Competitividad (Spain) AGL 2013-41188R (Other), University of Barcelona (Other)

Enrollment

Location

Arms

2.7

Actual Duration (Months)

21.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Biological Availability Nutritional Intervention Functional Food Nutrition Physiology	Other: Table Olives Other: Table Olives Other: Table Olives	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

58 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention 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.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)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Mar 25, 2019

Actual Primary Completion Date :

May 25, 2019

Actual Study Completion Date :

Jun 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 60 Arbequina Table Olives Pharmacokinetics Study	Other: Table Olives 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.
Experimental: 120 Arbequina Table Olives Pharmacokinetics Study	Other: Table Olives 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.
Experimental: 60 Table Olives Table Olives Nutritional Intervention	Other: Table Olives 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.
No Intervention: Control Control of Table Olives Nutritional Intervention

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institut de Recerca Hospital de la Santa Creu i Sant Pau - CIM Sant Pau	Barcelona		Spain	08041

Sponsors and Collaborators

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Ministerio de Economía y Competitividad (Spain) AGL 2013-41188R
University of Barcelona

Investigators

Study Director: Joana M Planas, PhD Prof., Departament de Bioquímica i Fisiologia. Facultat de Farmàcia i Ciències de l´Alimentació. Universitat de Barcelona