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Human Study of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT02273622
Recruitment Status : Completed
First Posted : October 24, 2014
Last Update Posted : March 24, 2015
Sponsor:
Information provided by (Responsible Party):
IMDEA Food

Brief Summary:
Explore the detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver).

Condition or disease Intervention/treatment Phase
Healthy Dietary Supplement: hydroxytyrosol Dietary Supplement: placebo Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Nutritional Intervention Study to Evaluate the Effect of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects
Study Start Date : October 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : January 2015

Arm Intervention/treatment
Experimental: hydroxytyrosol 5 mg
each participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo
Dietary Supplement: hydroxytyrosol
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.

Experimental: hydroxytyrosol 20 mg
each participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo
Dietary Supplement: hydroxytyrosol
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.

Placebo Comparator: placebo
each participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo
Dietary Supplement: placebo



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Number of participants with change in different anthropometrics parameters [ Time Frame: Change of Baseline and after one week hydroxytyrosol and placebo administration ]
    The different anthropometrics parameters are: weight, height, body mass index, fat mass, lean mass

  2. Number of participants with change in different biochemical parameters [ Time Frame: Change of Baseline and after one week hydroxytyrosol and placebo administration ]
    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).

  3. Concentration of hydroxytyrosol and metabolites in urine [ Time Frame: Change of Baseline and after one week hydroxytyrosol and placebo administration ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male gender with age range 20-40 years
  • Signed patient informed consent

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02273622


Locations
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Spain
IMDEA-Food
Madrid, Spain, 28049
Sponsors and Collaborators
IMDEA Food
Investigators
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Principal Investigator: Francesco Visioli, Prof IMDEA Food

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: IMDEA Food
ClinicalTrials.gov Identifier: NCT02273622     History of Changes
Other Study ID Numbers: IMD PI011
First Posted: October 24, 2014    Key Record Dates
Last Update Posted: March 24, 2015
Last Verified: October 2014

Keywords provided by IMDEA Food:
hydroxytyrosol
dietary supplement
gene expression regulation

Additional relevant MeSH terms:
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3,4-dihydroxyphenylethanol
Phenylethyl Alcohol
Anti-Infective Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Anti-Infective Agents, Local
Disinfectants