The objective of the study is to obtain information on the bioavailability and pharmacokinetics of the phenolics present in an olive leaf extract (Bonolive®, dose 250 mg), standardized on 40% oleuropein, and to identify the composition of the…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Bone disorders (excl congenital and fractures)
- Vascular injuries
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary aim of the study is to evaluate the bioavailability and
pharmacokinetics of the phenolics present in the olive leaf extract and the
metabolites which are formed upon administration of a dose which was previously
shown to have biological activity. Assessment and evaluation will be done by
analyzing the plasma and urinary concentrations of the main study parameter:
the olive phenolics oleuropein, hydroxytyrosol, tyrosol and their human
metabolites in the plasma and urine following a single oral consumption of the
olive leaf extract. To do this, blood samples will be collected pre-dose and
after 30 min, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 16h and 24h. Urine will be collected
and pooled as follows: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h.
Secondary outcome
Secondary study parameter 1: A first secondary aim, the bioavailability will be
compared for premenopausal and postmenopausal women, as differences in
circulating levels have been shown for specific phenolic compounds. As both
populations are of interest as target population for the olive extract under
study, comparison of potential differences in circulating metabolites is
important for extrapolation of the observed biological activity towards both
groups. To do this, pharmacokinetic parameters of the main circulating phenolic
metabolites in plasma will be compared for both groups.
Secondary study parameter 2: As second secondary study aim, the effect of the
bioavailable phenolics on the processes of osteoblastogenesis and adipogenesis
will be investigated in mesenchymal stem cells (MSCs) from human bone marrow.
To do this, blood samples collected from the individuals will be combined with
MSC cells in an ex vivo approach. This additional aim is included to obtain a
mechanistic link between the circulating levels of phenolics upon ingestion of
the product and the previously observed biological activity in relation to bone
formation processes.
Background summary
Olives, olive oils and products derived from olive trees (e.g. leaf extracts)
have generated significant interest due to their association with various
health-protective and therapeutic activities, into a large extent related to
the presence of high amounts of phenolic micronutrients such as oleuropein,
hydroxytyrosol and tyrosol. However, previous research has also shown that the
final bioavailability and biological activity greatly depends on the matrix in
which the olive phenolics are ingested (e.g. oil versus extract). Within a
certain matrix, e.g. olive leaf extracts, bioavailability may further be
influenced by the physical properties of the matrix, such as solubility under
aquatic conditions and the concentration in which the product is administered.
As only the bioavailable fraction of the olive phenolics may have biological
activity in the body, the amount of activity which reach systemic circulation
may have final health effects. Furthermore, as bioavailability of specific
phenolics has been shown to depend on circulating levels of female estrogens,
this may influence the final bioactivity of the olive phenolics, and therefore
selection of the study population can be of great importance.
Study objective
The objective of the study is to obtain information on the bioavailability and
pharmacokinetics of the phenolics present in an olive leaf extract (Bonolive®,
dose 250 mg), standardized on 40% oleuropein, and to identify the composition
of the metabolites which circulate in the body. This information will be used
to support the previously generated data regarding biological activity of the
extract in view of European Food Safety Authority (EFSA) health claim
submission. Moreover, differences in these parameters depending on the target
population will be assessed.
Study design
Parallel study design in which the olive leaf extract is administered to two
study groups of equal size (8 complete datasets per group). The intervention
will comprise the oral intake of a single capsule containing 250 mg of the
olive leaf extract.
Intervention
The study will consist of 1 study day in which each subject will consume the
olive leaf extract once.
Study burden and risks
After an overnight fasting, a catheter is placed in the arm of each subject for
repeated blood collection. During the study day, 11 times 12mL blood sample
will be taken. The participants are to refrain from products containing olives
or olive-derived products (e.g. olive oil or olive fruit or leaf extracts), all
sorts of alcohol, tea and vinegars for a period starting 3 days prior to the
start of each study day. The participants are asked not to change their normal
dietary habits before the study period. No adverse effects are expected.
Participants will not benefit directly from participation.
Oxfordlaan 70
6229 EV Maastricht
NL
Oxfordlaan 70
6229 EV Maastricht
NL
Listed location countries
Age
Inclusion criteria
-Female adults between 18 and 75 years old
-The study will consist of 8 premenopausal and 8 postmenopausal women.
-Only non*smoking individuals can participate. Non*smoking individuals are hereby defined as individuals who did not smoke during at least 6 months before the start of the study. Individuals who did not smoke for minimum 3 months prior to the study could also be included, upon evaluation and decision by the investigators.
-The participants are capable and willing to sign the Informed Consent Form at voluntary basis, after having received detailed information.
-The volunteers are considered healthy based on their medical history as questioned by the investigator during an interview and a general physical examination by the investigator.
-Female volunteers do not intend to become pregnant prior to or during the study and using adequate contraception.
-Premenopausal women should be on monophasic oral anti conception and the test day should not be in the pause week or in the first 3 days of pill use, in order to obtain a constant level of estrogen.
-The postmenopausal women should be at least 2 years post menopausal to ensure a homogeneous population
Exclusion criteria
-Clinically significant abnormal liver functioning (serum alanine and aspartate aminotransferase).
-Clinically significant abnormal serum creatinin.
-Abnormal BMI (i.e. lower than 18 or higher than 30).
-Use of concomitant medications or supplements.
-Blood donation during the last 4 weeks prior to the first dosing till 4 weeks after the last dosing.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| Other | 10566 |
| CCMO | NL38388.068.11 |
| OMON | NL-OMON21153 |