Condition category
Circulatory System
Date applied
14/03/2017
Date assigned
16/03/2017
Last edited
16/03/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
A high blood cholesterol level (hypercholesterolemia) causes an increased risk of cardiovascular (heart) disease, as cholesterol can build up in the arteries and lead to a myocardial infarction (heart attack). Diet changes are a useful strategy for the prevention of many diseases, especially those in which obesity is a risk factor, including cardiovascular disease. Phytosterols are vegetable substances similar to human cholesterol, but consuming them can control and even lower blood cholesterol levels. Similarly, omega-3 fatty acids, substances naturally found in fish and breast milk, have also been found to prevent cardiovascular disease. The aim of this study is to find out whether the daily intake of milk products enriched in phytosterols and omega-3 fatty acids can help prevent cardiovascular disease.

Who can participate?
Healthy adults between 25 and 70 years old who are overweight or obese

What does the study involve?
The study consists of two 28-day periods separated by a 4-week break. Participants are randomly allocated to one of two groups. The first group drink phytosterol-enriched milk in the first period and omega-3-enriched milk in the second period. The second group drink omega-3-enriched milk in the first period and PhyS-enriched milk in the second period. During the 2 weeks before the start of the study and the 4-week break, participants in both groups drink commercially available plain low-fat milk (without phytosterol or omega-3). All participants are requested to maintain their normal diet and physical activity throughout the study. Participants provide blood samples before and after each of the two periods to find out whether their cholesterol levels are affected.

What are the possible benefits and risks of participating?
The results of this study may show why regular intake of phytosterols and omega-3 fatty acids has health benefits. However, the individual participant may not benefit. There are no expected risks of participating in this study, except from the discomfort of blood sampling.

Where is the study run from?
Instituto Catalán de Ciencias Cardiovasculares (ICCC) - Hospital de la Santa Creu i Sant Pau (Spain)

When is the study starting and how long is it expected to run for?
February to July 2012

Who is funding the study?
1. Ministerio de Economía y Competitividad (Spain)
2. Instituto de Salud Carlos III (Spain)

Who is the main contact?
1. Prof. Lina Badimon
2. Dr Teresa Padro

Trial website

Contact information

Type

Scientific

Primary contact

Prof Lina Badimon

ORCID ID

http://orcid.org/0000-0002-9162-2459

Contact details

Instituto Catalán de Ciencias Cardiovasculares (ICCC)
Hospital de la Santa Creu i Sant Pau - Pavelló del Convent
Sant Antoni Maria Claret
167
08025 Barcelona
Barcelona
08025
Spain

Type

Scientific

Additional contact

Dr Teresa Padró

ORCID ID

http://orcid.org/0000-0003-1921-954X

Contact details

Instituto Catalán de Ciencias Cardiovasculares (ICCC)
Hospital de la Santa Creu i Sant Pau - Pavelló del Convent
Sant Antoni Maria Claret
167
08025 Barcelona
Barcelona
08025
Spain

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

ICCC-9 FITOCARD

Study information

Scientific title

Scientific basis of cardiovascular effects derived from the regular consumption of milk products supplemented with Phytosterols or omega-3 oils at systemic level in subjects at low cardiovascular risk with moderated hypercholesterolemia and overweight or obesity.

Acronym

FITOCARD

Study hypothesis

The main objective of this study is to characterize the differential proteomic profile and the lipidic profile of serum and plasma samples from healthy volunteers after the intake of a regular plain milk supplemented with either Phytosterols or Omega-3 fatty acids and to identify changes on any biomarker associated to the prevention of the cardiovascular risk.

Hypothesis: Low-fat milks supplemented with Phytosterols or long-chain n-3 PUFA have health benefits beyond their efficacy as lipid-lowering agents. Beneficial effects are evidenced through changes in plasma lipidomic and proteomic profiles as well as gene expression in peripheral blood cells that predisposes to lower cardiovascular risk. No adverse events will be observed.

Ethics approval

Ethics Committee for Clinical Research from the Hospital de la Santa Cruz y San Pablo, 05/07/2011, ref: 10/2011

Study design

Double-blind randomized two-arm longitudinal crossover study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Arteriosclerosis

Intervention

All subjects were submitted to two 28-day treatment sequences, separated by a 4 weeks washout period. Before the initiation of the intervention, individuals were submitted to a 2-week run-in period. During the run-in and wash-out periods, participants received 250 mL/day commercially available plain low-fat milk (without PhyS or ω-3), with the same composition to that used for preparing the PhyS-enriched- and ω-3 enriched milks.

At the end of the run-in period, subjects were randomly allocated to receive one of the two treatment sequences:
Study arm 1: Phytosterol (PhyS)-enriched milk in the first intervention period and ω-3 enriched milk in the second intervention period
Study arm 2: Omega-3 (ω3)-enriched milk in the first intervention period and PhyS-enriched milk in the second intervention period

Participants were instructed to consume a pack of milk (250 mL) per day, distributed in one or more portions according to their normal habits, replacing their habitual milk-products consumption. Subjects were requested to maintain their habitual diet at levels consistent with maintenance of a stable body weight and to continue their normal pattern of physical activity throughout the study period.

Lipid content varied from 0.4 g per 100 ml milk in the control low-fat milk to 0.8 g in the ω3-enriched milk and 0.9 g in the PhyS-enriched milk. The 20.6% of the lipid content in the ω3-enriched milk were omega-3 fatty acids, mainly consisting in EPA and DHA (150 mg EPA+DHA / 100 mL milk) that represented the 90.8% of the total omega-3 fatty acid content. In addition to lipid content, every 100 mL PhyS-enriched milk contained 0.64 g plant sterols (expressed as free PhyS). According to the provider’s information, the supplemented vegetable oil-based sterols (VEGAPURE® 95E) were mainly found as sterol esters (>94%) with 68% poly-unsaturated FA (C 18:2), 19% monounsaturated FA (18:1), and 13% saturated FA (16:0, 18:0). PhyS mix mainly consisted of sitosterol, campesterol, and stigmasterol (>77%), being sitostanol and campestanol the more abundant stanols. The content in other sterols/stanols did not exceed the 3%.

Intervention type

Supplement

Phase

Drug names

Primary outcome measures

1. Triglyceride and cholesterol levels, measured using biochemical analysis
2. Oxidative profile: measure of the lipidic peroxidation in plasma and LDL, the plasma antioxidant behavior and LDL resistance to oxidation
3. Fatty acids (FA) and lipidomic pattern measured in plasma and LDL samples respectively and analyzed by LC/MS/MS. The analysis of FA is performed after the derivatization of the samples to convert FAs into thrimethylaminoethyl esther iodide derivates. LDL lipidomic profile is analyzed in mixture with an internal lipid standard mixture
4. Proteomic profile:
4.1. Analysis of the differential proteomic profile of the lipid and lipid-free fraction of serum and plasma samples measured by 2DE electrophoresis, followed by protein identification by mass spectrometry identification (MALDI-TOF)
4.2. Validation of the results by western blot analysis and enzyme-linked immunosorbent assay (ELISA) kits
Measured at baseline and after each intervention period

Secondary outcome measures

1. Alcohol intake, smoking and dietary habits, taken from participants' medical records
2. Dietary habits, assessed using a questionnaire at baseline
3. Inflammatory variables related to atherosclerosis
4. Gene expression measured by RT-PCR and arrays either in the plasma or the blood cellular fraction after the intake of supplemented milk
5. Circulating microparticles assessed using blood samples or the cells of the vascular wall
6. Potential gene polymorphisms associated with the response to the interventions at protemic and lipidomic levels
Measured at baseline and after each intervention period

Overall trial start date

15/02/2012

Overall trial end date

20/07/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Healthy adult males and females between 25 and 70 years old
2. Overweight or grade 1 obese (body mass index greater than 25 kg/m^2)
3. Signed informed consent

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

35 participants (10% loss is accepted)

Participant exclusion criteria

1. Previous history of cardiovascular disease (ischaemic heart disease - angina or recent or old myocardial infarction, cerebral vascular accident, or peripheral vascular disease)
2. No documented cardiovascular disease (ischaemic heart disease - angina or recent or old myocardial infarction or previous or cerebral vascular accident, peripheral vascular disease)
3. Any disease affecting lipid metabolism
4. Any severe chronic disease
5. Lactose intolerance
6. Being in the phase of weight loss or expressing a desire for weight loss in the 4 months of the study
3. Alcohol consumption >60 g/day
7. Under treatment with fibrates or statins

Recruitment start date

15/02/2012

Recruitment end date

14/03/2012

Locations

Countries of recruitment

Spain

Trial participating centre

Instituto Catalán de Ciencias Cardiovasculares (ICCC) - Hospital de la Santa Creu i Sant Pau
Sant Antoni Maria Claret, 167
Barcelona
08025
Spain

Sponsor information

Organisation

Instituto Catalán de Ciencias Cardiovasculares (ICCC) - Hospital de la Santa Creu i Sant Pau

Sponsor details

Sant Antoni Maria Claret
167
Barcelona
08025
Spain

Sponsor type

Research organisation

Website

Funders

Funder type

Government

Funder name

Ministerio de Economía y Competitividad

Alternative name(s)

Ministry of Economy and Competitiveness, MINECO

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Spain

Funder name

Instituto de Salud Carlos III

Alternative name(s)

Institute of Health Carlos III, Carlos III Health Institute, ISCIII

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Spain

Results and Publications

Publication and dissemination plan

1. The results will be presented at the annual congress covering atherosclerosis, nutrition and biomarkers, as well as in novel omic technologies.
2. Three different publications are planned. These will specifically address the following areas: the lipid/lipidomic studies, the proteomic study, and the study on microparticles

IPD sharing plan
The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Teresa Padró

Intention to publish date

16/03/2019

Participant level data

Available on request

Results - basic reporting

Publication summary

2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/25773888

Publication citations

Additional files

Editorial Notes