Pivotal Assessment of the Effects of Bioactive on Health and Wellbeing. From Human Genome to Food Industry (PATHWAY-27)

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

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.

Study Overview

• Status: Terminated
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Dairy BEF; Dietary supplement: Bakery placebo; Dietary supplement: Egg placebo; Dietary supplement: Egg BEF; Dietary supplement: Dairy placebo; Dietary supplement: Bakery BEF

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Auvergne
    • Clermont-Ferrand, Auvergne, France, 63009
      • Centre de Recherche en Nutrition Humaine d'Auvergne
• Germany
  • Baden-Württemberg
    • Karlsruhe, Baden-Württemberg, Germany, 76131
      • Max Rubner-Institut
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • University of Bologna, Department of Medical and Surgical Sciences and Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi
• United Kingdom
  • Leeds, United Kingdom, LS2 9JT
    • University of Leeds

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dairy BEF + egg placebo + bakery placebo; 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; Dairy BEF: Milkshake powder enriched with 250 mg of DHA and 3g beta-glucans; Dietary supplement: Bakery placebo; Bakery placebo: Biscuits without enrichment; Dietary supplement: Egg placebo; Egg placebo: Frozen pancakes without enrichment
Active Comparator: Egg BEF + dairy placebo + bakery placebo; 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: Bakery placebo; Bakery placebo: Biscuits without enrichment; Dietary supplement: Egg BEF; Egg BEF: Frozen pancakes enriched with 250 mg of DHA and 320 mg of anthocyanins; Dietary supplement: Dairy placebo; Dairy placebo: Milkshake powder without enrichment
Active Comparator: Bakery BEF + dairy placebo + egg placebo; 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: Egg placebo; Egg placebo: Frozen pancakes without enrichment; Dietary supplement: Dairy placebo; Dairy placebo: Milkshake powder without enrichment; Dietary supplement: Bakery BEF; Bakery BEF: Biscuits enriched with 250 mg of DHA and 320 mg of anthocyanins
Placebo Comparator: All placebo; 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; Bakery placebo: Biscuits without enrichment; Dietary supplement: Egg placebo; Egg placebo: Frozen pancakes without enrichment; Dietary supplement: Dairy placebo; Dairy placebo: Milkshake powder without enrichment

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Collaborators: University of Bologna; University of Leeds; Centre de Recherche en Nutrition Humaine d'Auvergne; Max Rubner-Institut
• Investigators: Study Director: Alessandra Bordoni, MD, Department of Agro-Food Sciences and Technologies, University of Bologna

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): October 20, 2017
• Study Completion (Actual): October 20, 2017

Study Registration Dates

• First Submitted: February 18, 2016
• First Submitted That Met QC Criteria: March 3, 2016
• First Posted (Estimate): March 9, 2016

Study Record Updates

• Last Update Posted (Actual): December 2, 2017
• Last Update Submitted That Met QC Criteria: November 29, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: docosahexaenoic acid (DHA); bioactive; enriched foods; anthocyanins (AC); beta-glucans (BG)
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome
• Other Study ID Numbers: 147/2015/U/Sper

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual case report forms are available to collect study data into electronic form from all the recruiting centres. A central electronic database has been elaborated to capture, validate and manage the entered data by means of a variety of edit checks (e.g., subjecting the data to range checks, valid value checks, cross-checks, and manual review) that provide feedback to those entering/providing the data.