Condition category
Nutritional, Metabolic, Endocrine
Date applied
06/03/2012
Date assigned
09/05/2012
Last edited
25/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The aim of this study is to find out whether consuming olive oil enriched with olive oil phenolic compounds (OOPC) and olive oil enriched with OOPC plus flavonoids from thyme increases quality and quantity of high density lipoprotein (HDL) compared with consuming normal virgin olive oil.

Who can participate?
Male and female hypercholesterolemic (>200mg/dL) patients aged 20-80 years.

What does the study involve?
Participants will receive 25 ml per day of one of the three types of olive oil in three separate periods of 3 weeks, preceded each one by a 2-week wash-out period.

What are the possible benefits and risks of participating?
The benefit for the participants will be the possibility of reducing their cardiovascular disease risk. No harmful effects have been found to be associated with olive oil consumption.

Where is the study run from?
Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) , Barcelona, Spain

When is the study starting and how long is it expected to run for?
April to September 2012

Who is funding the study?
Spanish Ministry of Economy and Competitiveness

Who is the main contact?
Dr María-Isabel Covas
mcovas@imim.es
mfito@imim.es

Trial website

Contact information

Type

Scientific

Primary contact

Dr Maria Isabel Covas

ORCID ID

Contact details

Doctor Aiguader
88
Barcelona
08003
Spain
+34 (0)933 160 720
mcovas@imim.es

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

AGL2009-13517-C03-01

Study information

Scientific title

Virgin Olive oil and HDL Functionality (VOHF): a model for tailoring functional food: the VOHF project

Acronym

VOHF

Study hypothesis

A flavoured functional olive oil enriched not only with its own phenolics but also with complementary ones (regarding structure/function) from thyme could provide additional health benefits and consumers’ acceptation.

Ethics approval

Clinical Research Ethical Committee of the "Institut Municipal d’Assistència Sanitària (IMAS)", 09/09/2009, ref: 2009/3347/I

Study design

Randomized controlled double-blind cross-over single-centre clinical supplementation trial

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Other

Trial type

Quality of life

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Hypercholesterolemic patients

Intervention

Current interventions as of 23/04/2014:
Randomized, controlled, double-blind, cross-over, single-centre clinical supplementation trial, in which 33 subjects (19 men and 14 women) will be randomised to one of 3 orders of administration of 25 ml/day of raw:

1. Virgin olive oil (Control)
2. Functional Olive Oil 1 enriched with its own phenolic compounds (FOO1)
3. Functional Olive OIl 2 enriched with its olive oil phenolic compounds plus those of thyme (FOO2)

This will be in 3 periods of 3 weeks

Previous interventions:
Randomized, double-blind, cross-over, single-centre clinical supplementation trial, in which 30 subjects (15 men and 15 women) will be randomised to one of 3 orders of administration of:

1. 25 mL/day of raw refined virgin olive oil (Control)
2. Functional Olive Oil 1 enriched with its own phenolic compounds (FOO1)
3. Functional Olive OIl 2 enriched with its olive oil phenolic compounds plus those of thyme (FOO2)

This will be in 3 periods of 3 weeks

Intervention type

Supplement

Phase

Drug names

Primary outcome measures

1. HDL functionality:
The following parameters will be measured at baseline and before and after each intervention:
1.1. Markers of compliance: Measurement of tyrosol and hydroxytyrosol in spot morning urine will be performed by GC/mass spectrometry
1.2. Parameters of HDL functionality: Isolation of HDL will be done by sequential centrifugation.
2. The following parameters will be measured in isolated HDL:
2.1. Fatty acid content, vitamin E, and total phenolic content in HDL by HPLC-DAD
2.2. Apolipoproteins (Apo)A1, ApoA2, and ApoA4 by ELISA
2.3. Cholesterol esther transfer protein (CETP) and lecitine cholesterol acyl transferase (LCAT) by fluorometry
2.4. Paraoxonase (Organophosphatase activity) PON1) and PAF-AH activities by spectrometry with automated mode
2.5. 3’ chlorotyrosine and 3’-nitro-tyrosine by GC/MS
2.6. Bilayer fluidity of HDL will be measured by confocal microscopy. Cholesterol efflux from cells will be measured in culture of macrophages.
3. OMICS
Gene expression assay will be performed as previously described. Several candidate genes implicated in the increase of the HDL cholesterol and in the improvement of the HDL functionality in humans will be tested. Candidate genes: ABCA1: ATP-binding cassette, sub-family A (ABC1), member 1; ABCG1: ATP-binding cassette, sub-family G (WHITE), member 1; and ABCG4: ATP-binding cassette, sub-family G (WHITE), member 4 ApoA1: apolipoprotein A- I; and ApoE: apolipoprotein E; LPL: lipoprotein lipase; PAF-AH1B3: platelet-activating factor acetylhydrolase, isoform Ib, gamma subunit 29kDa; PPARalpha: peroxisome proliferator -activated receptor alpha; PPARgamma: peroxisome proliferator-activated receptor gamma; and PBPPAR: PPAR binding protein; RARA: retinoic acid receptor, alpha. Proteomic analyses, by separation with 2-DE (two-dimensional gel electrophoresis) and PMF (protein mass fingerprinting) with MALDI-TOF-MS (matrix -assisted laser desorption/ionization time of flight mass spectrometry ,will be performed in plasma samples.

Secondary outcome measures

Oxidative damage
The following parameters will be measured at baseline and before and after each intervention:
1. Plasma lipids will be performed by enzymatic methods in a automated mode. In vivo circulating oxidized LDL and 3’ chlorotyrosine derivates in urine will be determined by ELISA
2. Protein carbonyl content (PCC) by spectrometry
3. 8-isoprostane (8-epi PGF2á)
4. 8-hydroxydeoxyguanosine (8-OHdG) by enzyme-linked immunosorbent assay (ELISA)

Added 23/04/2014:
5. Endothelial function
6. Intestinal microorganism study

Overall trial start date

02/04/2012

Overall trial end date

07/09/2012

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 23/04/2014:
1. Hypercholesterolemic patients (>200 mg/dL)
2. Aged 20-80 years

Previous inclusion criteria:
1. Hyperlipidemic patients
2. Patients with low (<40 mg/dL) HDL cholesterol
3. Aged 20-60 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

33

Participant exclusion criteria

Current exclusion criteria as of 25/04/2014:
1. Smokers
2. Athletes with PA >3000 kcal/day
3. BMI >35 kg/m2
4. Diabetes, multiple allergies, intestinal diseases
5. Any condition that limits the mobility of the subject making study visits impossible
6. Life threatening illness such as cancer or severe disease with a lowered expected 3 year survival
7. Any other disease or condition that would worsen the adherence to the measurements or treatment

Previous exclusion criteria:
1. Intake of antioxidant supplement or acetylsalicylic acid or any other drug with established antioxidative properties
2. Athletes with PA >3000 kcal/week in leisure-time
3. Obesity (BMI > 30 kg/m2)
4. Diabetes, multiple allergies, intestinal diseases
5. Any condition that limits the mobility of the subject making study visits impossible
6. Life threatening illness such as cancer or severe disease with a lowered expected 3 year survival
7. Any other disease or condition that would worsen the adherence to the measurements or treatment

Recruitment start date

02/04/2012

Recruitment end date

07/09/2012

Locations

Countries of recruitment

Spain

Trial participating centre

Doctor Aiguader, 88
Barcelona
08003
Spain

Sponsor information

Organisation

Spanish Ministry of Economy and Competitiveness (Spain)

Sponsor details

MINECO
Former Spanish Ministry of Science and Technology
Secretaría General de Innovación
Albacete
5
Madrid
28027
Spain
+34 (0)902 218 600
cauidi@micinn.es

Sponsor type

Government

Website

http://www.mineco.gob.es

Funders

Funder type

Government

Funder name

Spanish Ministry Science and Technology (Spain) ref: AGL2009-13517-C03-01

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26061039

Publication citations

Additional files

Editorial Notes

25/04/2016: Publication reference added. On 23/04/2014 the following changes were made to the trial record: 1. The disease/condition/study domain field was changed from 'Hyperlipidemic patients with low HDL cholesterol' to 'Hypercholesterolemic patients' 2. The target number of participants was changed from 30 to 33.