Effects of Enzymatic Digestion and Probiotic on Oleuropein Bioavailability

Study Overview
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Brief Summary
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This is a 3-arms randomized-controlled, parallel group, single center, double-blind study investigating the bioavailability of olive oil extract (OLE) in two different OLE formulations (enzymatically treated and co-administered with a probiotic) compared to original OLE formulation in healthy adult subjects.

Detailed Description
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Male or female healthy adults between 25 and 65 years of age will be randomized into one of the 3 following groups to receive: Capsule of OLE + 1 stick of maltodextrin Capsule of OLE enzymatically treated + 1 stick of maltodextrin Capsule OLE + 1 stick of probiotic 52 subjects will be randomized to achieve 15 subjects per group to complete the trial. The study will involve 3 phases: PK1 (all subjects will receive one capsule of OLE in the morning and blood samples will be collected at different timepoints for 24h) followed by a washout period of 1 day 3 weeks intervention (subjects will receive the product thy have benn assigned to) followed by a wash-out period of 3 days PK2 period (subjects will receive one capsule the product thy have benn assigned to

Official Title
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Effects of Enzymatic Digestion and Probiotic on Oleuropein Bioavailability

Conditions
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Healthy Subjects

Intervention / Treatment
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* Dietary Supplement: OLE enzymatically treated
* Dietary Supplement: OLE + probiotic
* Dietary Supplement: OLE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to sign written informed consent prior to trial entry Male or female healthy adults between 25 and 65 years of age Body Mass Index (BMI) within the range 18.5 - 29.9 (both inclusive) In good health as determined by medical judgment and medical history Exclusion Criteria: Any food allergy/intolerance Subjects not willing and/or not able to comply with scheduled visits and the requirements of the study protocol Taking or anticipated initiation of any lipid-modifying or blood-clotting medication e.g. statins, cholesterol lowering Smokers Alcohol intake higher than 2 servings per day (one serving is 0.4 dL of strong alcohol, 1 dL of wine, or 3 dL of beer) or drug abuse Receiving or having received antibiotics in the past 4 weeks prior to the day of inclusion Overly imbalanced or restrictive diet (e.g. hyperproteic, vegan, ketogenic, etc.) Hormonal treatment for women linked to menopause (contraceptive treatment accepted) Pregnancy or breastfeeding Supplements or foods containing probiotics (yogurts allowed) Currently participating or having participated in another clinical trial within 4 weeks prior to trial start

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 3-arms randomized-controlled, parallel group, single center, double-blinded study investigating 3 different formulations of the investigational product
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OLE enzymatically treated<br>Participants will receive 1 capsule of OLE enzymatically treated + 1 stick of maltodextrin each day in the morning for 21 days | Dietary Supplement: OLE enzymatically treated<br>* OLE (Olive leaf extract ) enzymatically treated + maltodextrin<br>|
| Experimental: OLE + probiotic<br>Participants will receive 1 capsule of OLE + 1 stick of probiotic each day in the morning for 21 days | Dietary Supplement: OLE + probiotic<br>* OLE (Olive leaf extract) co-administered with probiotic<br>|
| Active Comparator: OLE<br>Participants will receive 1 capsule of OLE + 1 stick of maltodextrin each day in the morning for 21 days | Dietary Supplement: OLE<br>* OLE (Olive leaf extract) + maltodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-24h of individual blood oleuropein metabolites during PK2 period | AUC0-24h (concentration/time curve) of individual blood oleuropein metabolites during PK2 period | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax during PK2 period | Cmax of total and individual oleuropein metabolites during PK2 period | 24 hours | 
| Tmax during PK2 period | Tmax of total and individual oleuropein metabolites during PK2 period | 24 hours | 
| T1/2 during PK2 period | T1/2 of total and individual oleuropein metabolites during PK2 period | 24 hours | 
| Levels of total and individual oleuropein metabolites in urine at PK2 | Levels of total and individual oleuropein metabolites excreted in the urine collected over 24 hours during PK2 | 24 hours | 
| AUC0-24h during PK1 | AUC0-24h (concentration/time curve) of individual blood oleuropein metabolites during PK1 period | 24 hours | 
| Cmax during PK1 | Cmax of total and individual blood oleuropein metabolites during PK1 period | 24 hours | 
| Tmax during PK1 | Tmax of total and individual blood oleuropein metabolites during PK1 period | 24 hours | 
| T1/2 during PK1 | T1/2 of total and individual blood oleuropein metabolites during PK1 period | 24 hours | 
| Levels of total and individual oleuropein metabolites in urine at PK1 | Levels of total and individual oleuropein metabolites excreted in the urine collected over 24 hours during PK1 | 24 hours | 
| Change in gut microbiota bacterial population diversity | Change from baseline to end of the 3-week intervention period of gut microbiota bacterial population diversity (16SrDNA sequencing) | 3 weeks | 
| Change in levels of faecal oleuropein metabolites | Change from baseline to end of the 3-week intervention period of faecal oleuropein metabolites | 3 weeks |