Pivotal Assessment of the Effects of Bioactive on Health and Wellbeing. From Human Genome to Food Industry

Study Overview
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Brief Summary
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This is a multi-centre, randomised, double-blind, placebo-controlled, parallel-arm dietary intervention study. In total, 800 men and women at risk for Metabolic Syndrome (MS) will be recruited. Subjects will be eligible to the study if they present with two to four of the MS diagnostic criteria, at least one of them being: fasting triglycerides ≥150 mg/dL but ≤400 mg/dL OR HDL-cholesterol ≤50 mg/mL in women, ≤ 40mg/mL in men (with fasting triglycerides ≥110 mg/dL). Each of the four recruiting centres will recruit 200 volunteers. Participants will be randomly assigned to one of four groups to receive either: Dairy BEF + egg placebo + bakery placebo Egg BEF + dairy placebo + bakery placebo Bakery BEF + dairy placebo + egg placebo Dairy, egg and bakery placebo Participants will be required to consume all three of the allocated products each day for 12 weeks. Eligible volunteers will be included and randomly allocated to one of the four groups. At baseline, 6 weeks and 12 weeks after inclusion, each participant will visit the recruiting centre for clinical and biochemical investigations. At 3 weeks and 9 weeks participants will complete questionnaires relating to their satisfaction with the food products, compliance to consumption of the study food products, and any gastrointestinal side effects or health-related adverse events that have occurred in the previous 3 weeks. At each recruiting centre 40 participants will be required to take part in additional activities, these are: stool sample collection, adipose tissue aspiration, body composition analysis by dual energy x-ray absorptiometry (DEXA) and assessment of physical activity.

Official Title
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Investigation of the Effect of Daily Consumption of Bioactive Enriched Foods (BEF) on Biochemical and Anthropometric Markers of Metabolic Syndrome (MS)

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Dietary Supplement: Dairy BEF
* Dietary Supplement: Egg BEF
* Dietary Supplement: Bakery BEF
* Dietary Supplement: Bakery placebo
* Dietary Supplement: Dairy placebo
* Dietary Supplement: Egg placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects presenting with two to four diagnostic criteria for metabolic syndrome, at least one of them being elevated fasting triglycerides OR HDL-cholesterol ≤50 mg/mL in women, ≤ 40mg/mL in men (with fasting triglycerides ≥110 mg/dL). Exclusion Criteria: subjects with five clinical criteria for metabolic syndrome Regular drug therapy with impact on serum lipids; Diabetes (fasting glucose > 1.26 g/L, or anti-diabetic treatment); Celiac disease, lactose intolerance, allergy to milk or egg proteins; Antibiotic treatment within the last 3 months; Recent history of cancer or cancer treatment (less than 2 years); Active or recently diagnosed intestinal malabsorption; Diagnosis of organ failure Familial dyslipidemia (TG ≥ 4.5 mmol/l or 400 mg/dl); Illegal drug use or chronic alcoholism or smoking; Intensive physical exercise (≥ 5 hour/week); Consumption of nutritional supplements containing DHA, BG or AC; History of allergy or intolerance to any components used in BEF; Women who are pregnant or lactating;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dairy BEF + egg placebo + bakery placebo<br>200 subjects consuming every day for 12 weeks: 1 portion of Dairy BEF + 1 portion of Egg placebo + 1 portion of Bakery placebo | Dietary Supplement: Dairy BEF<br>* Dairy BEF: Milkshake powder enriched with 250 mg of DHA and 3g beta-glucans<br>Dietary Supplement: Bakery placebo<br>* Bakery placebo: Biscuits without enrichment<br>Dietary Supplement: Egg placebo<br>* Egg placebo: Frozen pancakes without enrichment<br>|
| Active Comparator: Egg BEF + dairy placebo + bakery placebo<br>200 subjects consuming every day for 12 weeks: 1 portion of Egg BEF + 1 portion of Dairy placebo + 1 portion of Bakery placebo | Dietary Supplement: Egg BEF<br>* Egg BEF: Frozen pancakes enriched with 250 mg of DHA and 320 mg of anthocyanins<br>Dietary Supplement: Bakery placebo<br>* Bakery placebo: Biscuits without enrichment<br>Dietary Supplement: Dairy placebo<br>* Dairy placebo: Milkshake powder without enrichment<br>|
| Active Comparator: Bakery BEF + dairy placebo + egg placebo<br>200 subjects consuming every day for 12 weeks: 1 portion of Bakery BEF + 1 portion of Dairy placebo + 1 portion of Egg placebo | Dietary Supplement: Bakery BEF<br>* Bakery BEF: Biscuits enriched with 250 mg of DHA and 320 mg of anthocyanins<br>Dietary Supplement: Dairy placebo<br>* Dairy placebo: Milkshake powder without enrichment<br>Dietary Supplement: Egg placebo<br>* Egg placebo: Frozen pancakes without enrichment<br>|
| Placebo Comparator: All placebo<br>200 subjects consuming every day for 12 weeks: 1 portion of Egg placebo + 1 portion of Dairy placebo + 1 portion of Bakery placebo | Dietary Supplement: Bakery placebo<br>* Bakery placebo: Biscuits without enrichment<br>Dietary Supplement: Dairy placebo<br>* Dairy placebo: Milkshake powder without enrichment<br>Dietary Supplement: Egg placebo<br>* Egg placebo: Frozen pancakes without enrichment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Triglycerides blood levels (mg/dl) | Change from baseline in triglycerides blood levels after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. | Baseline and 12 weeks | 
| HDL-cholesterol blood levels (mg/dl) | Change from baseline in HDL-cholesterol blood levels after 12 weeks of consumption of foods | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood glucose (mg/dl). | Change from baseline in blood glucose levels after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. | Baseline and 12 weeks | 
| Blood pressure (mmHg) | Change from baseline in blood pressure after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. | Baseline and 12 weeks | 
| Waist circumference (cm). | Change from baseline in waist circumference after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. | Baseline and 12 weeks | 
| Urinary food metabolite levels (parts per millions). | Changes from baseline in urinary food metabolite levels, after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. | Baseline and 12 weeks | 
| Fecal microbiota composition (analysis of principal coordinates - PCOA) | Changes in fecal bacterial composition and diversity will be determined at baseline and after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. The predominant microbial community and specific functional groups will be characterized by next-generation sequencing (NGS) of the 16S rDNA gene. The interindividual differences in the composition of the intestinal microbiota (beta-diversity) will be evaluated with the analysis of principal coordinates (PCOA). Appropriate statistical analysis will be performed to evaluate significant differences in the relative abundance of the microbial groups of intestinal microbiota between different groups of subjects. | Baseline and 12 weeks | 
| Fecal Short Chain Fatty Acids (parts per million). | Change from baseline in production/uptake in the stool of Short Chain Fatty Acids, after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. | Baseline and 12 weeks | 
| Dna methylation levels (%). | To test whether lymphocytes may be useful as a surrogate for adipose tissue to detect changes in DNA methylation and gene expression, genome-wide methylation differences will be performed in parallel in lymphocytes and fat cells from baseline and after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. Expression of affected genes will be evaluated by qRT-PCR. | Baseline and 12 weeks | 
| Serum Hemoglobin A1c (HbA1c) levels (%) | Change from baseline in HbA1c levels, after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. | Baseline and 12 weeks | 
| Homeostasis Model Assessment (HOMA) Index levels. | Change from baseline in Homeostasis Model Assessment Index levels, after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. | Baseline and 12 weeks | 
| Fecal metabolite levels (parts per millions). | Change from baseline in food metabolite levels in the stools after 12 weeks of consumption of foods enriched with DHA, alone or in combination with AC or BG, in subjects at risk for or affected by MS. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bioactive, enriched foods, anthocyanins (AC), beta-glucans (BG), docosahexaenoic acid (DHA)