HealthyNCT02273622
Human Study of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects
A study testing hydroxytyrosol in people with Healthy, run by IMDEA Food at 1 site in Spain.
Trial summary
Explore the detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver). Read more about this study
- Who is it for?
- Ages 20 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- hydroxytyrosol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteSpain
- Study dates
- Oct 2014to Jan 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male gender with age range 20-40 years
- Signed patient informed consent
Who cannot join
- BMI < 19 and >26
- Subjects with a diagnosis of diabetes mellitus, dyslipidemia, hypertension and other cardiometabolic diseases.
- Subjects with dementia, mental illness or diminished cognitive function.
- Subjects with serious diseases (hepatic, renal, cardiovascular, etc.)
- Subjects who refuse to make the 24 hour urine collection and blood samples under study.
- Subjects with allergy or intolerance to olive and derivatives.
- Subjects with drug treatment of any kind.
- Current smoking.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Nutritional Intervention Study to Evaluate the Effect of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects
Explore the detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver).
Read the detailed description
Hydroxytyrosol is peculiar to olives (and, hence, to olive oil) and is being exploited as a potential supplement or preservative to be employed in the nutraceutical, cosmeceutical, and food industry. One of the properties described for the hydroxytyrosol is its high antioxidant activity. Also, hydroxytyrosol is able to modulate several enzymatic activities linked to cardiovascular disease. Animal experiments confirm hydroxytyrosol retains its antioxidant activity once ingested (though the human metabolic pathway has been elucidated and shows extensive glucuronidation and subsequent urinary excretion), protects from second hand smoke-induced oxidative damage, inhibits platelet aggregation, ameliorates lipid profile and decreases atherosclerosis development, increases brain cell resistance to oxidation and mitochondrial membrane potential Several mechanisms have been proposed to explain how biologically polyphenols protect against degenerative diseases. It is now thought more likely that some phytochemicals, including polyphenols, are processed by the body as xenobiotics. They stimulate stress- related cell signalling pathways that result in increased expression of genes encoding cytoprotective genes. Nrf2 (NF-E2-related factor 2) is a transcription factor which binds to the Antioxidant Response Element (ARE) in cells and thus regulates enzymes involved in antioxidant functions or detoxification (e.g. thioredoxin reductase-1 and glutathione peroxidases). Polyphenols might increase gene transcription of Nrf2 mediated by such response elements. This provides grounds for the theory of hormesis, i.e. when mild stress triggers defense mechanisms. In the case of polyphenols it indicates how they could have an indirect antioxidant action.
That is why plans to carry this study to explore the detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver). It´ll be a randomized crossover, pilot study examining the effects of two doses of hydroxytyrosol, in the form of a commercially-available raw mixture: 1) providing 5 mg/d; 2) 25 mg/d, for one week with a one-week washout period in between, during 6 weeks.
The investigators will recruit 20 healthy volunteers, from within those who participate in the Genyal Platform studies AT IMDEA-Food Institute.
- Conditions
- Healthy
- Being tested
- hydroxytyrosol, placebo
- Keywords
- hydroxytyrosol, dietary supplement, gene expression regulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hydroxytyrosolDietary supplement
Pilot study with 20 participants, each participant will alternately by the two arms of the study (hydroxytyrosol 5 mg and 20 mg) and control, during 6 weeks.
placeboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| hydroxytyrosol 5 mg | Experimental | each participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo Receives: Dietary Supplement: hydroxytyrosol |
| hydroxytyrosol 20 mg | Experimental | each participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo Receives: Dietary Supplement: hydroxytyrosol |
| placebo | Placebo comparator | each participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo Receives: Dietary Supplement: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver).
The analyses of gene expression will be carried out at the ad-hoc platform in use at IMDEA-Food (see www.food.imdea.org for details). Total RNA will be extracted from mononuclear cells with TRI Reagent (Sigma-Aldrich, Inc., St. Louis, MO, USA) and purified with RNeasy MiniElute Cleanup Kit (Qiagen, Hilden, Germany). Recovered RNA will be quantified using a Nanodrop ND-1000 v3.5.2 spectrophotometer (Nanodrop TechnologyR, Cambridge, UK). RNA integrity will be assessed using 1.6% agarose gel, 1× TBE. RNA will be judged suitable for array hybridization only if samples exhibited intact bands corresponding to 18S and 28S ribosomal RNAs. During the study blood samples will be obtained from venous puncture and blood samples will be collected in tubes containing EDTA, maintained on ice and rapidly centrifuged to obtain plasma. Plasma will be immediately distributed in aliquots for the different determinations and stored at -70 °C until analysis.
Measured: Change of Baseline and after one week hydroxytyrosol and placebo administration
Secondary outcomes (3)
Number of participants with change in different anthropometrics parameters
The different anthropometrics parameters are: weight, height, body mass index, fat mass, lean mass
Measured: Change of Baseline and after one week hydroxytyrosol and placebo administration
Number of participants with change in different biochemical parameters
The different biochemical parameters are: Lipid profile (TG, CT, LDL-C, HDL-C), oxidation (LDL-ox, 8-iso PGF2α), inflammatory (PCRu, TNFα, IL1β, VCAM1, ICAM; TXB2).
Measured: Change of Baseline and after one week hydroxytyrosol and placebo administration
Concentration of hydroxytyrosol and metabolites in urine
Urine sampling will be performed before administration of the substance (t=0) and after 24 h post dose. Urinary HT and metabolites will be measured by mass spectrometry
Measured: Change of Baseline and after one week hydroxytyrosol and placebo administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2014
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- IMDEA Food
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Francesco Visioli, Prof, Principal investigator, IMDEA Food
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02273622
- Sponsor's protocol ID
- IMD PI011
- Status last verified
- Oct 2014
- First submitted
- 15 Oct 2014
- Last updated
- 24 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Visioli F, Galli C, Plasmati E, Viappiani S, Hernandez A, Colombo C, Sala A. Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress. Circulation. 2000 Oct 31;102(18):2169-71. doi: 10.1161/01.cir.102.18.2169.
PubMed 11056087Visioli F, Galli C, Bornet F, Mattei A, Patelli R, Galli G, Caruso D. Olive oil phenolics are dose-dependently absorbed in humans. FEBS Lett. 2000 Feb 25;468(2-3):159-60. doi: 10.1016/s0014-5793(00)01216-3.
PubMed 10692578Visioli F, Caruso D, Plasmati E, Patelli R, Mulinacci N, Romani A, Galli G, Galli C. Hydroxytyrosol, as a component of olive mill waste water, is dose- dependently absorbed and increases the antioxidant capacity of rat plasma. Free Radic Res. 2001 Mar;34(3):301-5. doi: 10.1080/10715760100300271.
PubMed 11264904Visioli F, Bellosta S, Galli C. Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages. Life Sci. 1998;62(6):541-6. doi: 10.1016/s0024-3205(97)01150-8.
PubMed 9464466Crespo MC, Tome-Carneiro J, Burgos-Ramos E, Loria Kohen V, Espinosa MI, Herranz J, Visioli F. One-week administration of hydroxytyrosol to humans does not activate Phase II enzymes. Pharmacol Res. 2015 May-Jun;95-96:132-7. doi: 10.1016/j.phrs.2015.03.018. Epub 2015 Mar 30.
PubMed 25836918
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nutritional Intervention Study to Evaluate the Effect of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02273622
- Acronym / sponsor ID
- IMD PI011
- Conditions
- Healthy
- Keywords
- hydroxytyrosol, dietary supplement, gene expression regulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- IMDEA FoodUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 24 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Explore the detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver).
Detailed description
Hydroxytyrosol is peculiar to olives (and, hence, to olive oil) and is being exploited as a potential supplement or preservative to be employed in the nutraceutical, cosmeceutical, and food industry. One of the properties described for the hydroxytyrosol is its high antioxidant activity. Also, hydroxytyrosol is able to modulate several enzymatic activities linked to cardiovascular disease. Animal experiments confirm hydroxytyrosol retains its antioxidant activity once ingested (though the human metabolic pathway has been elucidated and shows extensive glucuronidation and subsequent urinary excretion), protects from second hand smoke-induced oxidative damage, inhibits platelet aggregation, ameliorates lipid profile and decreases atherosclerosis development, increases brain cell resistance to oxidation and mitochondrial membrane potential Several mechanisms have been proposed to explain how biologically polyphenols protect against degenerative diseases. It is now thought more likely that some phytochemicals, including polyphenols, are processed by the body as xenobiotics. They stimulate stress- related cell signalling pathways that result in increased expression of genes encoding cytoprotective genes. Nrf2 (NF-E2-related factor 2) is a transcription factor which binds to the Antioxidant Response Element (ARE) in cells and thus regulates enzymes involved in antioxidant functions or detoxification (e.g. thioredoxin reductase-1 and glutathione peroxidases). Polyphenols might increase gene transcription of Nrf2 mediated by such response elements. This provides grounds for the theory of hormesis, i.e. when mild stress triggers defense mechanisms. In the case of polyphenols it indicates how they could have an indirect antioxidant action.
That is why plans to carry this study to explore the detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver). It´ll be a randomized crossover, pilot study examining the effects of two doses of hydroxytyrosol, in the form of a commercially-available raw mixture: 1) providing 5 mg/d; 2) 25 mg/d, for one week with a one-week washout period in between, during 6 weeks.
The investigators will recruit 20 healthy volunteers, from within those who participate in the Genyal Platform studies AT IMDEA-Food Institute.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| hydroxytyrosol 5 mg | Experimental | Dietary Supplement: hydroxytyrosoleach participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo |
| hydroxytyrosol 20 mg | Experimental | Dietary Supplement: hydroxytyrosoleach participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo |
| placebo | Placebo comparator | Dietary Supplement: placeboeach participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Male gender with age range 20-40 years
- Signed patient informed consent
Key exclusion criteria (8 listed)
- BMI < 19 and >26
- Subjects with a diagnosis of diabetes mellitus, dyslipidemia, hypertension and other cardiometabolic diseases.
- Subjects with dementia, mental illness or diminished cognitive function.
- Subjects with serious diseases (hepatic, renal, cardiovascular, etc.)
- Subjects who refuse to make the 24 hour urine collection and blood samples under study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hydroxytyrosolPilot study with 20 participants, each participant will alternately by the two arms of the study (hydroxytyrosol 5 mg and 20 mg) and control, during 6 weeks. | Dietary supplement | hydroxytyrosol 20 mg, hydroxytyrosol 5 mg |
| placebo | Dietary supplement | placebo |
Primary outcome
Detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver).
Time frame: Change of Baseline and after one week hydroxytyrosol and placebo administration
The analyses of gene expression will be carried out at the ad-hoc platform in use at IMDEA-Food (see www.food.imdea.org for details). Total RNA will be extracted from mononuclear cells with TRI Reagent (Sigma-Aldrich, Inc., St. Louis, MO, USA) and purified with RNeasy MiniElute Cleanup Kit (Qiagen, Hilden, Germany). Recovered RNA will be quantified using a Nanodrop ND-1000 v3.5.2 spectrophotometer (Nanodrop TechnologyR, Cambridge, UK). RNA integrity will be assessed using 1.6% agarose gel, 1× TBE. RNA will be judged suitable for array hybridization only if samples exhibited intact bands corresponding to 18S and 28S ribosomal RNAs. During the study blood samples will be obtained from venous puncture and blood samples will be collected in tubes containing EDTA, maintained on ice and rapidly centrifuged to obtain plasma. Plasma will be immediately distributed in aliquots for the different determinations and stored at -70 °C until analysis.
3 secondary outcomes
Number of participants with change in different anthropometrics parameters
Time frame: Change of Baseline and after one week hydroxytyrosol and placebo administration
Number of participants with change in different biochemical parameters
Time frame: Change of Baseline and after one week hydroxytyrosol and placebo administration
Concentration of hydroxytyrosol and metabolites in urine
Time frame: Change of Baseline and after one week hydroxytyrosol and placebo administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2015.
- Background: PubMed 11056087Visioli F, Galli C, Plasmati E, Viappiani S, Hernandez A, Colombo C, Sala A. Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress. Circulation. 2000 Oct 31;102(18):2169-71. doi: 10.1161/01.cir.102.18.2169.
- Background: PubMed 10692578Visioli F, Galli C, Bornet F, Mattei A, Patelli R, Galli G, Caruso D. Olive oil phenolics are dose-dependently absorbed in humans. FEBS Lett. 2000 Feb 25;468(2-3):159-60. doi: 10.1016/s0014-5793(00)01216-3.
- Background: PubMed 11264904Visioli F, Caruso D, Plasmati E, Patelli R, Mulinacci N, Romani A, Galli G, Galli C. Hydroxytyrosol, as a component of olive mill waste water, is dose- dependently absorbed and increases the antioxidant capacity of rat plasma. Free Radic Res. 2001 Mar;34(3):301-5. doi: 10.1080/10715760100300271.
- Background: PubMed 9464466Visioli F, Bellosta S, Galli C. Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages. Life Sci. 1998;62(6):541-6. doi: 10.1016/s0024-3205(97)01150-8.
- Derived from this study: PubMed 25836918Crespo MC, Tome-Carneiro J, Burgos-Ramos E, Loria Kohen V, Espinosa MI, Herranz J, Visioli F. One-week administration of hydroxytyrosol to humans does not activate Phase II enzymes. Pharmacol Res. 2015 May-Jun;95-96:132-7. doi: 10.1016/j.phrs.2015.03.018. Epub 2015 Mar 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Visioli, Prof principal investigator
IMDEA Food
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing hydroxytyrosol in people with Healthy, run by IMDEA Food at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver). (time frame: Change of Baseline and after one week hydroxytyrosol and placebo administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02273622, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2015.