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

• Sponsor: King's College London (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT04179136
• Collaborator: (none)
• Enrollment: 68
• Location: 1
• Arms: 4
• Anticipated Duration (Months): 14.2
• Patients Per Site Per Month: 4.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Dietary Supplement: lignan capsules contain 300 mg flaxseed (SDG) extract; Dietary Supplement: Placebo treatment matching intervention	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double blinded randomized control trialDouble blinded randomized control trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: The Role of Gut Microbiome on Cardiovascular Health Benefits of Dietary Lignans ( CardioFlax Study).
• Actual Study Start Date: Nov 25, 2019
• Anticipated Primary Completion Date: Jan 30, 2021
• Anticipated Study Completion Date: Jan 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: High enterolactone producer's (intervention) lignan capsules contain 300 mg flaxseed (SDG) extract	Dietary Supplement: lignan capsules contain 300 mg flaxseed (SDG) extract; lignan capsules contain 300 mg flaxseed (SDG) extract
Placebo Comparator: High enterolactone producer's (Control) Placebo treatment matching intervention	Dietary Supplement: Placebo treatment matching intervention; Placebo treatment matching intervention
Active Comparator: Low enterolactone producer's (intervention) lignan capsules contain 300 mg flaxseed (SDG) extract	Dietary Supplement: lignan capsules contain 300 mg flaxseed (SDG) extract; lignan capsules contain 300 mg flaxseed (SDG) extract
Placebo Comparator: Low enterolactone producer's (Control) Placebo treatment matching intervention	Dietary Supplement: Placebo treatment matching intervention; Placebo treatment matching intervention

Outcome Measures

Primary Outcome Measures

1. Change in flow-mediated dilation (FMD) [Baseline vs 8 weeks post-consumption]

   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)

Secondary Outcome Measures

1. Change in flow-mediated dilation (FMD) [Day 0, Day1 post-consumption]

   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.

2. Change in office blood pressure [Day 0, Day 1 and 8 weeks post-consumption]

   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.

3. Change in pulse wave velocity (PWV) [Baseline vs 8 weeks post-consumption]

   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

4. Change in augmentation Index (AIx) [Baseline vs 8 weeks post-consumption]

   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

5. Change in Total cholesterol [Baseline vs 8 weeks post-consumption]

   To investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids Total cholesterol after 8 weeks daily consumption

6. Change in blood inflammatory markers (IL-6) [Baseline vs 8 weeks post-consumption]

   To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on inflammation markers (IL-6) after 8 weeks daily consumption.

7. Change in glucose marker [Baseline vs 8 weeks post-consumption]

   To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on glucose levels (glucose) after 8 weeks daily consumption.

8. Change in blood lipid (HDL cholesterol ) concentrations [Baseline vs 8 weeks post-consumption]

   o investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids (HDL)after 8 weeks daily consumption

9. Change in blood lipid (LDL cholesterol )concentrations [Baseline vs 8 weeks post-consumption]

   o investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids( LDL cholesterol) after 8 weeks daily consumption

10. Change in blood lipid (triglycerides) concentrations [Baseline vs 8 weeks post-consumption]

    o investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids (triglycerides) after 8 weeks daily consumption

11. Change in blood inflammatory markers (CRP) [Baseline vs 8 weeks post-consumption]

    To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on inflammation markers ( CRP) after 8 weeks daily consumption.

12. Change in insulin markers [Baseline vs 8 weeks post-consumption]

    To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on glucose levels (insulin) after 8 weeks daily consumption.

13. Change in glucose (HbA1c) markers [Baseline vs 8 weeks post-consumption]

    To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on glucose levels (HbA1c) after 8 weeks daily consumption.

Other Outcome Measures

1. Change in metabolic (poly)phenol metabolite concentrations [Baseline, 24 hand 8 weeks post-consumption]

   To determine the plasma levels of polyphenol metabolites after acute and chronic consumption of flaxseed lignans (SDG).Measured by liquid chromotography-mass spectrometry (LC/MS)

2. Change in metabolic (poly)phenol metabolite concentrations [Baseline vs 8 weeks post-consumption]

   To determine the urine levels of polyphenol metabolites baseline and chronic consumption of flaxseed lignans (SDG). Measured by liquid chromotography-mass spectrometry (LC/MS)

3. Gut microbiome composition [Baseline vs 8 weeks post-consumption]

   To investigate changes in gut microbiota composition and diversity after 8 weeks consumption of flaxseed lignans (SDG) extract.

4. Menopausal symptoms [Baseline vs 8 weeks post-consumption]

   To investigate the effect of 300 mg flaxseed lignans (SDG) extract vs Placebo on menopausal symptoms using menopausal questionnaire for women over 45 years.

5. Homeostatic model assessment [Baseline vs 8 weeks post-consumption]

   To assess insulin resistance (IR) using homeostatic model assessment (HOMA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	King's College London	London		United Kingdom	SE1 9NH

Sponsors and Collaborators

• King's College London

Investigators

• Principal Investigator: Dr.Ana Rodriguez-Mateos, PhD, King's College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: King's College London
• ClinicalTrials.gov Identifier: NCT04179136
• Other Study ID Numbers: CardioFlax study
• First Posted: Nov 27, 2019
• Last Update Posted: Dec 11, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by King's College London: Cardiovascular system Polyphenols

Study Results

No Results Posted as of Dec 11, 2019