Phenulin: Effect of Cranberry and Agaves Extract on Microbiota and Intestinal Health

Sponsor

Laval University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03800277

Collaborator

Ministry of Agriculture, Fisheries and Food, Quebec (Other), Ministry of economic development, innovation and export trade, Quebec (Other), Fruit d Or, Quebec (Other), Diana Food, Symrise (Other), Atrium Innovations (Industry), NutriAgaves, Mexico (Other), Nestlé (Industry)

Enrollment

Location

Arms

28.8

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The growing prevalence of obesity and type 2 diabetes (T2D) is a major public health problem. Recent studies have clearly established that the gut microbiota plays a key role in the investigator's propensity to develop obesity and associated metabolic health disorders. The gut microbiota compositions plays a decisive role in glucose metabolism and the chronic inflammatory state associated with insulin resistance. Consuming prebiotic rich diet, including polyphenol and inulin rich food could help modulate favorably the gut microbiota which could lead to a reduction of endotoxemia and beneficial metabolic health effects.

Condition or Disease	Intervention/Treatment	Phase
Endotoxemia Metabolic Syndrome Glucose Metabolism Disorders Insulin Resistance	Dietary Supplement: Cranberry Dietary Supplement: Agaves Dietary Supplement: Placebo	N/A

Detailed Description

It is now recognized that overweight individuals have altered microbiota which could lead to intestinal barrier defects and chronic inflammation disorders. Polyphenols such as Proanthocyanidins may modulate the gut microbiota thereby providing beneficial effects on metabolic health. Inulin is a well known prebiotic that could stimulate growth of favorable bacteria in the gut.

The overall goal is to determine the efficacy and synergy of a supplement of polyphenols from cranberry extract with or without a supplement of inulin from agaves to reduce chronic inflammation and endotoxemia and to improve glucose metabolism and insulin sensitivity by modulating microbiota of overweight human subjects with metabolic syndrome symptoms.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Effect of Prebiotic Supplementation on Metabolic Endotoxemia and Modulation of the Gut Microbiota: Double-blind, Controlled and Randomized Parallel Clinical Study of the Efficacy and Synergistical Effect of Cranberry Polyphenols and Inulin From Agaves

Actual Study Start Date :

Nov 5, 2018

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Mar 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cranberry and Agaves Cranberry extract (2 capsules) + Agaves powder (1 single-dose packet)	Dietary Supplement: Cranberry Supplementation of polyphenols from cranberry extract Dietary Supplement: Agaves Supplementation of inulin from Agaves powder
Experimental: Cranberry and placebo Cranberry extract (2 capsules) + Placebo powder (1 single-dose packet)	Dietary Supplement: Cranberry Supplementation of polyphenols from cranberry extract Dietary Supplement: Placebo Supplementation with placebo
Experimental: Placebo and Agaves Placebo (2 capsules) + Agaves powder (1 single-dose packet)	Dietary Supplement: Agaves Supplementation of inulin from Agaves powder Dietary Supplement: Placebo Supplementation with placebo
Placebo Comparator: Placebo and placebo Placebo (2 capsules) + Placebo powder (1 single-dose packet)	Dietary Supplement: Placebo Supplementation with placebo

Outcome Measures

Primary Outcome Measures

Change in metabolic endotoxemia: Measure concentration of Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP) in plasma [At the beginning and the end of treatment (10 weeks)]
effect of the supplements on variation in plasma concentration of LPS and LBP

Secondary Outcome Measures

Change in intestinal permeability: Measure concentration of zonulin in plasma [At the beginning and the end of treatment (10 weeks)]
effect of the supplements on plasma concentration of zonulin
Change in inflammation state of the tissue: Measure concentration of calprotectin and lactoferrin in feces [At the beginning and the end of treatment (10 weeks)]
effect of the supplements on fecal calprotectin and lactoferrin
Change in systemic inflammation: Measure concentration of inflammation biomarkers in the serum [At the beginning and the end of treatment (10 weeks)]
effect of the supplements on chronic inflammation (serum concentration of hsCRP, Il-6, TNF-alpha, IL-1 beta, IL-23)
Change in glucose serum concentration [At the beginning and the end of treatment (10 weeks)]
effect of the supplements on serum concentration of glucose
Change in insulin and C-peptide serum concentration [At the beginning and the end of treatment (10 weeks)]
effect of the supplements on serum concentration of insulin and C-peptide
Change in microbiota diversity: growth of Akkermancia muciniphila, Lactobacillus, Prevotella, Bifdobacterium and inhibition of Clostridium perfringens, C. difficile, Bacteroides spp.) [At the beginning and the end of treatment (10 weeks)]
Global variation of the fecal microbiota and gut microbiota profiling

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

overweight (BMI 25-39.9 kg/m2)
fasting insulin over 60 pmol/L or fasting glucose 5.6 - 6.9 mmol/L
hsCRP 1-10 mg/L
at least one of the following criteria: waist circumference ≥ 80 cm (women) and ≥94 cm (men); Tg ≥ 1.7 mmol/L; blood pressure ≥ 130/85 mmHg; HDL < 0,9 mmol/L
non-smoking
eating fruits and vegetables less then 5 portions/day

Exclusion Criteria:

chronic disease
taking drugs or natural health products that could affect glucose or lipid metabolism
taking anti-inflammatory, antiacids
taking pre or probiotics
inflammatory bowel disease
antibiotics in the past 3 months
allergy or intolerance to cranberries or agaves
Major surgery in the past 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute of nutrition and functional foods, Laval University	Québec	Quebec	Canada	G1V 0A6

Sponsors and Collaborators

Laval University
Ministry of Agriculture, Fisheries and Food, Quebec
Ministry of economic development, innovation and export trade, Quebec
Fruit d Or, Quebec
Diana Food, Symrise
Atrium Innovations
NutriAgaves, Mexico
Nestlé

Investigators

Principal Investigator: Hélène Jacques, PhD, Institute of nutrition and functional foods, Laval University
Study Director: Yves Desjardins, PhD, Institute of nutrition and functional foods, Laval University