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

Coronary Artery Disease Clinical Trial

— RISMED  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02578329
• Other study ID #: R194/14 - CCM203
• Status: Recruiting
• Phase: N/A
• First received: July 23, 2015
• Last updated: June 6, 2016
• Start date: July 2015
• Est. completion date: February 2018

Study information

• Verified date: June 2016
• Source: Centro Cardiologico Monzino
• Contact: Fabrizio Veglia, PhD
• Phone: +39 025800
• Email: fabrizio.veglia[@]ccfm.it
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: February 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

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
• usual low-fat dietary advice
usual low-fat dietary advice for cardiovascular disease

Locations

Country	Name	City	State
Italy	Centro Cardiologico Monzino, IRCCS	Milan	MI

Sponsors (1)

Lead Sponsor	Collaborator
Centro Cardiologico Monzino

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No