Condition category
Digestive System
Date applied
20/02/2017
Date assigned
28/04/2017
Last edited
08/05/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Intestinal permeability is a term describing the control of material passing from inside the gut, through the gut wall to the rest of the body. Leaky gut syndrome is a condition that occurs when the gut lining becomes abnormally permeable, when tiny openings develop in the gut wall. This allows substances to pass through the gut wall that would normally be blocked. The microorganisms that naturally live in the gut (intestinal microbiota) are an important regulator of gut permeability. Diet is an important factor that shapes the composition of the intestinal microbiota. Polyphenols are important nutrients derived from plant-based foods that have been shown to improve health. The aim of this study is to find out what effect eating a diet rich in polyphenols has on health and intestinal permeability in the elderly.

Who can participate?
Adults aged 60 and over who have a leaky gut.

What does the study involve?
Participants are randomly allocated to one of two groups, which consume two study diets in a random order for eight weeks, with an eight week period of consuming their usual diet in between. The first diet involves eating three potions of polyphenol-rich foods every day, such as berries and derived products, blood oranges and derived products, pomegranate juice, renetta apple and purée, green tea and dark chocolate products. The second diet involves eating a similar diet without the addition of the polyphenol-rich foods. Before and after each eight week diet, participants have blood, urine and stool samples collected in order to evaluate the impact of the diet of their health and intestinal permeability.

What are the possible benefits and risks of participating?
Consuming more polyphenol rich products may help to reduce intestinal permeability and therefore improve intestinal function. There are no notable risks involved with participating.

Where is the study run from?
1. Ministry of Agricultural, Food and Forestry Policies (Italy)
2. Biotechnology and Biological Sciences Research Council (UK)
3. Ministry of Economy, Industry and Competitiveness (Spain)

When is the study starting and how long is it expected to run for?
May 2016 to March 2019

Who is funding the study?
Fondazione Opera Immacolata Concezione (OIC foundation) (Italy)

Who is the main contact?
Professor Patrizia Riso
patrizia.riso@unimi.it

Trial website

Contact information

Type

Scientific

Primary contact

Prof Patrizia Riso

ORCID ID

http://orcid.org/0000-0002-9204-7257

Contact details

DeFENS - Department of Food
Environmental and Nutritional Sciences
Division of Human Nutrition
University of Milan
Milan
20133
Italy
+39 0250316726
patrizia.riso@unimi.it

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Gut and blood microbiomics for studying the effect of a polyphenol-rich dietary pattern on intestinal permeability in the elderly

Acronym

MaPLE

Study hypothesis

A polyphenols rich diet can reduce Intestinal Permeability (IP) in a way that is beneficial for the Intestinal Barrier (IB), resulting in reduced IP and decreased translocation of inflammogenic bacterial factors from the digestive tract into the bloodstream and an improvement of intestinal microbial ecosystem (IME).

Ethics approval

Ethics Committee of the University of Milan, 15/02/2016, ref: 6/16 CE_15.02.16_Verbale_All-7

Study design

Randomised controlled cross over study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Other

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Intestinal permeability (IP)

Intervention

Based on a computer randomization plan, subjects are randomized to receive the two study diets in a random order. Participants follow the diets for eight weeks, followed by an eight week washout period where they follow their regular diet and then the other diet for eight weeks.

Polyphenol-rich (PR)-diet: Participants consume a diet developed to double the amount of polyphenols intake (as recorded in the population under study) providing three portion of polyphenol-rich food products daily (i.e about 750 mg of total polyphenols are added to the amount regularly introduced). The following polyphenol-rich products have been considered in the PR-diet: berries and derived products, blood oranges and derived products, pomegranate juice, renetta apple and purée, green tea and dark chocolate products.

The control diet (C-diet): Participants consume a comparable diet for eight weeks without thepolyphenol-rich products.

Before and after each study diet period (at baseline, 8, 16 and 24 weeks), participants provide blood, urine and stool samples.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Intestinal permeability is evaluated by measuring Zonulin serum levels using an ELISA kit at baseline, 8, 16 and 24 weeks.

Secondary outcome measures

1. Fecal microbiota composition evaluated by 16S rRNA gene profiling with MiSeq-Illumina platform at baseline, 8, 16 and 24 weeks
2. Short chain fatty acids and polyphenol-derived metabolites measured with LC-MS system at baseline, 8, 16 and 24 weeks
3. Diet-induced changes in microbiota metabolism performed by NMR at baseline, 8, 16 and 24 weeks
4. LC-MS analysis are used for faecal water at baseline, 8, 16 and 24 weeks
5. Total blood bacterial load are assessed through a quantitative real-time PCR; taxomic profile investigated by 16S rRNA gene profiling with MiSeq-Illumina platform at baseline, 8, 16 and 24 weeks
6. Inflammatory markers, oxidative stress and related markers e.g. vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1 performed through ELISA kit at baseline, 8, 16 and 24 weeks
7. DNA damage assessed through Comet Assay at baseline, 8, 16 and 24 weeks
8. Endotoxin by Limulus Amebocyte Lysate (LAL) assay assessed to evaluate the inflammatory process and oxidative stress modulation at baseline, 8, 16 and 24 weeks
9. Metabolomic analysis will be performed on HPLC-ESI-Q-ToF-MS and NMR to understand the interaction of the polyphenol rich diet with the secondary metabolites of microbiota at baseline, 8, 16 and 24 weeks

Overall trial start date

02/05/2016

Overall trial end date

28/03/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age > 60 years old
2. Intestinal Permeability evaluated by Zonulin serum level
3. Adequate nutritional status evaluated with Mini Nutritional Assessment (MNA) score ≥24
4. Good cognitive status tested with Mini Mental State Evaluation (MMSE) score ≥24
5. Self-sufficiency assessed with validated tests (e.g. Barthel index - activities of daily living, Tinetti balance assessment)

Participant type

Healthy volunteer

Age group

Senior

Gender

Both

Target number of participants

60 elderly people

Participant exclusion criteria

1. Celiac disease
2. Severe liver disease with cirrhosis
3. Severe renal insufficiency (dialysis)
4. Presence of Chronic Obstructive Pulmonary severe COPD (oxygen therapy for many hours a day) or severe heart failure, i.e. class III or IV NYHA - New York Heart Association
5. Antibiotic treatment
6. Malignant tumor that required treatment in the previous 2 years

Recruitment start date

01/06/2016

Recruitment end date

01/06/2017

Locations

Countries of recruitment

Italy

Trial participating centre

Fondazione Opera Immacolata Concezione (OIC foundation)
Via Toblino, 53
Padua
35142
Italy

Sponsor information

Organisation

European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI - HDHL)

Sponsor details

Laan van Nieuw Oost Indië 334
Den Haag
2593
Netherlands

Sponsor type

Other

Website

http://www.healthydietforhealthylife.eu

Funders

Funder type

Government

Funder name

Ministero delle Politiche Agricole Alimentari e Forestali

Alternative name(s)

Ministry of Agricultural, Food and Forestry Policies, Ministero delle Politiche Agricole, Alimentari e Forestali, MiPAAF

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Italy

Funder name

Biotechnology and Biological Sciences Research Council

Alternative name(s)

BBSRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

PCIN-2015-238 Ministry of Economy, Industry and Competitiveness, Spanish government

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication of study results in high-impact peer reviewed journals following trial completion.

IPD Sharing plan:
The current data sharing plans for the study are unknown and will be made available at a later date.

Intention to publish date

28/03/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes