The Role of Gut Microbiome on Cardiovascular Health Benefits of Dietary Lignans (CardioFlax Study).

Study Overview
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Brief Summary
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The aim of this study is to investigate the effects of gut microbial metabolism of flaxseed lignans on cardiovascular health. Enterolactone is the main gut microbial metabolite of lignans. The study population will be stratified in low and high enterolactone producers and will investigate whether high producers will have greater benefits than low producers, and whether low producers may become high producers after daily consumption of lignans over 8 weeks. The investigators will evaluate changes in endothelial function, blood pressure, arterial stiffness, insulin resistance, lipid profile and gut microbiome composition after 8 weeks daily consumption of flaxseed lignans.

Detailed Description
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Epidemiological studies have shown inverse relation between enterolactone levels and cardiovascular mortality. Participants will be stratified from first phase (NCT03573414) and then randomly allocated to treatment or placebo. Outcomes are measured at baseline and after 8 weeks post consumption.

Official Title
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The Role of Gut Microbiome on Cardiovascular Health Benefits of Dietary Lignans ( CardioFlax Study).

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Dietary Supplement: lignan capsules contain 300 mg flaxseed (SDG) extract
* Dietary Supplement: Placebo treatment matching intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy women aged 20-70 years BMI between 18 and 35 kg/m2 Subjects are willing to maintain their normal eating/drinking habits and exercise habits to avoid changes in body weight over the duration of the study Are able to understand the nature of the study Able to give signed written informed consent Signed informed consent form Exclusion Criteria: Medical history of cardiovascular disease including coronary artery disease, cerebrovascular disease and peripheral artery disease Hypertensive, as defined as SBP superior or equal to 140 mmHg, and CBP superior or equal to 90 mmHg Participants with BMI superior to 35 kg/m2, and BMI below 18 kg/m2 Medical history of diabetes mellitus, metabolic syndrome, terminal renal failure or malignancies Abnormal heart rhythm (lower or higher than 60-100 bmp) Allergies to flaxseed or other significant food allergy Subjects under medication that can affect the cardiovascular system or on vitamin/dietary supplements. Subjects who have lost more than 10% of their weight in the past 6 months or are currently in a diet Subjects who reported participant in another study within one month before the study start Smoker Subjects Pregnant women or planning to become pregnant in the next 6 months Any reason or condition that in the judgment of the clinical investigator(s) may put the subject at unacceptable risk or that may preclude the subject from understanding or complying with the study's requirements.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blinded randomized control trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High enterolactone producer's (intervention)<br>lignan capsules contain 300 mg flaxseed (SDG) extract | Dietary Supplement: lignan capsules contain 300 mg flaxseed (SDG) extract<br>* lignan capsules contain 300 mg flaxseed (SDG) extract<br>|
| Placebo Comparator: High enterolactone producer's (Control)<br>Placebo treatment matching intervention | Dietary Supplement: Placebo treatment matching intervention<br>* Placebo treatment matching intervention<br>|
| Active Comparator: Low enterolactone producer's (intervention)<br>lignan capsules contain 300 mg flaxseed (SDG) extract | Dietary Supplement: lignan capsules contain 300 mg flaxseed (SDG) extract<br>* lignan capsules contain 300 mg flaxseed (SDG) extract<br>|
| Placebo Comparator: Low enterolactone producer's (Control)<br>Placebo treatment matching intervention | Dietary Supplement: Placebo treatment matching intervention<br>* Placebo treatment matching intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in flow-mediated dilation (FMD) | To investigate the effect of daily consumption of 300 mg of flaxseed (SDG) extract vs Placebo for 8 weeks on endothelium-dependent flow mediated dilation (FMD) of the brachial artery (0, 8 weeks) | Baseline vs 8 weeks post-consumption | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in flow-mediated dilation (FMD) | To investigate the acute effect of 300 mg of flaxseed (SDG) extract vs Placebo on endothelium-dependent flow mediated dilation (FMD) of the brachial artery after 24- hour post-consumption. | Day 0, Day1 post-consumption | 
| Change in office blood pressure | To investigate the effect of 300 mg flaxseed lignans (SDG) extract vs Placebo on peripheral systolic and diastolic blood pressure, and heart rate after 8 weeks daily consumption. | Day 0, Day 1 and 8 weeks post-consumption | 
| Change in pulse wave velocity (PWV) | To determine the effect of 300 mg of lignans (SDG) vs Placebo on pulse wave velocity (PWV ) using a Sphygmocor device, after 8 weeks daily consumption | Baseline vs 8 weeks post-consumption | 
| Change in augmentation Index (AIx) | To determine the effect of 300 mg of lignans (SDG) vs Placebo on augmentation index (PWA) using a Sphygmocor device, after 8 weeks daily consumption | Baseline vs 8 weeks post-consumption | 
| Change in Total cholesterol | To investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids Total cholesterol after 8 weeks daily consumption | Baseline vs 8 weeks post-consumption | 
| Change in blood inflammatory markers (IL-6) | To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on inflammation markers (IL-6) after 8 weeks daily consumption. | Baseline vs 8 weeks post-consumption | 
| Change in glucose marker | To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on glucose levels (glucose) after 8 weeks daily consumption. | Baseline vs 8 weeks post-consumption | 
| Change in blood lipid (HDL cholesterol ) concentrations | o investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids (HDL)after 8 weeks daily consumption | Baseline vs 8 weeks post-consumption | 
| Change in blood lipid (LDL cholesterol )concentrations | o investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids( LDL cholesterol) after 8 weeks daily consumption | Baseline vs 8 weeks post-consumption | 
| Change in blood lipid (triglycerides) concentrations | o investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids (triglycerides) after 8 weeks daily consumption | Baseline vs 8 weeks post-consumption | 
| Change in blood inflammatory markers (CRP) | To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on inflammation markers ( CRP) after 8 weeks daily consumption. | Baseline vs 8 weeks post-consumption | 
| Change in insulin markers | To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on glucose levels (insulin) after 8 weeks daily consumption. | Baseline vs 8 weeks post-consumption | 
| Change in glucose (HbA1c) markers | To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on glucose levels (HbA1c) after 8 weeks daily consumption. | Baseline vs 8 weeks post-consumption | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular system Polyphenols