An Intervention Study to Assess the Effect of the Mediterranean Diet on the Plasma Fatty Acid Profile (RISMED)

A Randomized Intervention Study to Assess the Effect of the Mediterranean Diet on the Plasma Fatty Acid Profile

The purpose of this study is to determine whether a Mediterranean Diet, personalized in terms of total calories, total lipids and balanced in terms of saturated, mono- and poly-unsaturated lipids, corrects the adverse fatty acid profile of patients with CHD and reduces markers of oxidative stress and inflammation more effectively than a low-fat dietary advice.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Behavioral: Intensively advised Mediterranean diet; Behavioral: usual low-fat dietary advice

Detailed Description

Geographical differences in the incidence of CardioVascular Disease (CVD) show a lower risk in countries of south Europe compared with north and east Europe and USA. The Mediterranean Diet (MD) has been the most frequently invoked factor to explain these differences, but the underlying mechanisms are still unclear. On the other hand, blood fatty acid (FA) composition has been shown to be strongly related to cardiovascular risk, presumably through changes in oxidative stress and inflammatory pathways, two mechanisms involved in the pathogenesis of atherothrombosis. Preliminary data from our group suggest that patients with Coronary Heart Disease (CHD) adhere less to features of MD and exhibit a different fatty acid profile compared to healthy subjects. We speculate that MD may reduce oxidative stress and inflammatory markers, and reverse the unfavorable blood fatty acid profile observed in patients with CHD. Even though single MD components (wine, olive oil, vegetables, fish, etc) have shown beneficial effects on oxidative stress, inflammation and CardioVascular (CV) risk, evidence indicates that these effects are mostly related to the extent of compliance with the whole MD, which comprises possible synergism between food components. For this reason, the present study will consider the whole MD and not single components.

Design: randomized, parallel groups, open-label, intervention trial. Intervention: an intensively advised MD (fatty fish at least 3 times/week; legumes 2-3 times/ week; vegetables twice a day; fruits twice/day; 30-45g olive oil/day; 1-2 glasses of red wine/day, not more than 150g red meat/week), personalized in terms of calories, total lipids and balanced in terms of saturated, mono- and poly-unsaturated lipids (n= 75) vs. usual low-fat dietary advice (n=75) for 3 months. Participants: males and females, age 30-75, with a recent history of coronary revascularization, randomized after clinical stabilization (at least 60 days after any coronary procedure or event).

At baseline and after intervention in both groups:

Dietary assessment: using the EPIC questionnaire, a well validated dietary recall tool.

Blood, urinary and fecal samples: routine biochemical determinations, blood fatty acid composition by gas-chromatography, C reactive protein and oxidative stress markers (urinary isoprostanes, whole blood reduced and oxidized glutathione by Liquid Chromatography- Mass Spectrometry (LC-MS/MS), plasma alpha- and gamma-tocopherol by High Performance Liquid Chromatography (HPLC) with fluorimetric detector), gene expression and/or epigenome in peripheral whole blood cells (as an index of global changes of inflammation/immune response), intestinal microbiome.

Statistical analysis: Principal component analysis to characterize fatty acid patterns. Score of Trichopoulou to assess adherence to MD.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • MI
    • Milan, MI, Italy, 20138
      • Recruiting
      • Centro Cardiologico Monzino, IRCCS
      • Contact: Monica G Giroli, PhD; Phone Number: 2617 +39 02 5800; Email: monica.giroli@ccfm.it
      • Contact: Fabrizio Veglia, PhD; Phone Number: 2827 +39 02 5800; Email: fabrizio.veglia@ccfm.it
      • Sub-Investigator: José P Werba, MD
      • Sub-Investigator: Viviana M Cavalca, PhD
      • Sub-Investigator: Patrizia Risé

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical diagnosis of coronary artery disease
• recent history of a first coronary revascularization
• at least 60 days after any coronary procedure or event
• age between 30 and 75 years

Exclusion Criteria:

• diagnosis of diabetes mellitus
• food intolerance to any component of the mediterranean diet
• BMI < 19 or > 33
• assuming drugs or food supplements with omega-3 fatty acids or natural or synthetic antioxidants.
• patients already adherent to a full mediterranean diet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Med Diet; Intensively advised Mediterranean diet	Behavioral: Intensively advised Mediterranean diet; Mediterranean Diet: fatty fish 3 times/week; legumes 2-3 times/week; vegetables twice/day; fresh fruits twice/day; 30 to 45g olive oil/day; 1-2 glasses red wine/day; less than 150g red meat/week
Active Comparator: Low Fat diet; usual low-fat dietary advice	Behavioral: usual low-fat dietary advice; usual low-fat dietary advice for cardiovascular disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of whole blood fatty acid profile	Urinary isoprostanes (8-iso-PGF2-alpha will be measured at randomization and after dietary intervention by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods.	three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Mediterranean diet on urinary isoprostanes	Urinary isoprostanes (8-iso-PGF2-alpha will be measured at randomization and after dietary intervention by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods.	three months
Effect of Mediterranean diet on oxidized glutathione	Whole blood oxidized glutathione (GSSG) will be measured at randomization and after dietary intervention by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods.	three months
Effect of Mediterranean diet on reduced glutathione	Whole blood reduced glutathione (GSH) will be measured at randomization and after dietary intervention by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods.	three months
Effect of Mediterranean diet on plasma Vitamin E	Plasma vitamin E (alpha- and gamma-tocopherol) will be measured at randomization and at the end of the study by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods.	three months
Effect of Mediterranean diet on Low-grade systemic inflammatory status	Effect of Mediterranean diet on Low-grade systemic inflammatory status will be assessed at randomization and at the end of the study by high sensitivity C-Reactive protein (hs-CRP) measured by immunoturbidimetry	three months
Effect of Mediterranean diet on peripheral blood transcriptome	Whole transcriptome analysis will be performed by next-generation sequencing (NGS) on whole-blood derived RNA at randomization and after dietary intervention. Comparisons will be made between the two groups (MD vs. control diet). The outcome measure will be significant differential expression (fold-change) both at gene and gene-set levels.	three months
Significant differences in the relative abundance of the operational taxonomic units (OTU) within subjects	Changes in gut bacterial composition (microbiome) will be assessed by massive parallel sequencing of the hypervariable regions of the 16S (Svedberg) rRNA (ribosomal ribonucleic acid) gene on genomic DNA isolated from stool samples at the three time-points, in order to identify the intestinal bacterial phylotypes. The outcome measure will be significant differences in the relative abundance of the operational taxonomic units (OTU) within subjects	three months

Collaborators and Investigators

• Sponsor: Centro Cardiologico Monzino

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): February 1, 2018

Study Registration Dates

• First Submitted: July 23, 2015
• First Submitted That Met QC Criteria: October 15, 2015
• First Posted (Estimate): October 16, 2015

Study Record Updates

• Last Update Posted (Estimate): June 7, 2016
• Last Update Submitted That Met QC Criteria: June 6, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Mediterranean diet; blood fatty acid
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: R194/14 - CCM203