Effects of Polyphenols on Iron Absorption in Iron Overload Disorders. (POLYFER)

March 29, 2019 updated by: University Hospital, Clermont-Ferrand
Dysmetabolic iron overload syndrome and genetic hemochromatosis are frequent causes of iron overload. Polyphenols are efficient iron-chelators. Investigator hypothesize that polyphenol supplementation can reduce iron absorption in iron overload disease. Iron absorption can be studied by the area-under-the-curve of serum iron after iron oral loading. The primary outcome is the decrease of post-prandial serum iron after rich-iron meal, due to polyphenol supplementation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Iron overload diseases are highly prevalent. Dysmetabolic iron overload syndrome involves 15% of men with metabolic syndrome X. Genetic hemochromatosis is the most common genetic disease in Northern Europe. Both are due to a lack of regulation in iron absorption. To date, there is no nutritional study for those patients.

Polyphenols, particularly flavanols, have shown as good iron-chelating abilities as pharmacological chelators. However, no human study in iron-overload disease have been so far conducted.

The aim of POLYFER-study is to demonstrate that oral polyphenol intake reduces iron absorption in patients with genetic or metabolic iron-overload diseases.

POLYFER is a cross-over randomized controlled trial comparing the effect of polyphenol supplementation versus placebo on iron absorption after loading dose of iron given through a rich-iron meal. Iron absorption will be studied by the area under the curve of serum iron after the meal. Serum iron will be collected after the meal à 0 minute, 30 minutes, 1 hour, 2 hours, 3 hours et 4 hours.

Because of the nycthemeral variations of serum iron, it is essential to obtain a collection of serum iron data in the basal state (after fasting), allowing the calculation for each subject of a "relative" AUC after iron-rich meal with placebo and after iron-rich meal with polyphenols. The endpoint will be the difference between "relative" AUC after meal rich in iron alone and after polyphenols.

In order to improve the underlying mechanism of atherosclerosis which is highly prevalent in those diseases, we will conduct an ancillary study. Recent studies showed interesting results linking some oxylipins levels and inflammation. Investigator will study basal oxylipin level and post-prandial oxylipin level by lipidomic analysis in both diseases.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clermont-Ferrand, France, 63003
        • CHU Clermont-Ferrand

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 years old and over
  • Written consent.
  • For DIOS Group : at least one criteria of the metabolic syndrome as defined by the International Diabetes Federation, associated with hepatic iron overload measured by MRI (at least 50 µmol/g) or by hepatic biopsy.
  • For Genetic Haemochromatosis type 1 Group: homozygosity mutation C282Y in HFE gene ; patients undergoing therapeutic phlebotomies.

Exclusion Criteria:

  • Persons under guardianship
  • Body-weight less than 45 kg
  • Hemoglobin less than 9 g/dL.
  • Intestinal malabsorption of any cause
  • Current use or previous use during the last 2 months of iron supplement.
  • Current use or previous use during the last 2 months of treatment interacting with iron absorption (increasing like C vitamin or decreasing like iron chelators)
  • Other causes of hyperferritinemia : chronic inflammatory syndrome, porphyria, hyperferritinemia-cataract-syndrome, chronic alcohol consumption, chronic hemolysis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Polyphenols
patients will receive during the meal, 2 capsules of Oligopin® containing 50 mg of polyphenols each. They will take the two capsules simultaneously with a glass of water, after the starter. Each capsule of Oligopin® contains two excipients: 150 mg of maltodextrin and 30 mg of magnesium stearate.
Dietary supplement: polyphenols

After 6 hours of fasting, each patient will eat a complete meal course, containing 40 mg of iron, at two different days (wash-out period: 3 days between each meal).

During each meal, each patient will receive, two capsules containing polyphenols or two placebo capsules (cross-over methodology). The meal in which each patient will receive either polyphenol or placebo will be randomized.

The diet consists of :

  • Starter: duck gizzard salad.
  • Main course: black pudding and pasta.
  • French cheese.
  • Fruits: kiwi fruit.

This diet contain approximately 40 mg of iron, with low polyphenol intake. Patients will be asked to eat the whole gizzard and black pudding to ensure the highest iron intake.

At the end of the meal, blood samples will be collected at 0 minute, 30 minutes, 1 hour, 2 hours, 3 hours and 4 hours, to assess serum iron level, in order to measure the area under the curve of iron kinetic.
Experimental: Placebo
patients will receive during the meal, 2 capsules of placebo, visually identical to Oligopin®. The patient will take the two capsules simultaneously with a glass of water, after the starter. Each capsule of placebo contains two excipients: 218.9 mg of maltodextrin and 1.1 mg of magnesium stearate.
Other: Placebo

After 6 hours of fasting, each patient will eat a complete meal course, containing 40 mg of iron, at two different days (wash-out period: 3 days between each meal).

During each meal, each patient will receive, two capsules containing polyphenols or two placebo capsules (cross-over methodology). The meal in which each patient will receive either polyphenol or placebo will be randomized.

The diet consists of :

  • Starter: duck gizzard salad.
  • Main course: black pudding and pasta.
  • French cheese.
  • Fruits: kiwi fruit.

This diet contain approximately 40 mg of iron, with low polyphenol intake. Patients will be asked to eat the whole gizzard and black pudding to ensure the highest iron intake.

At the end of the meal, blood samples will be collected at 0 minute, 30 minutes, 1 hour, 2 hours, 3 hours and 4 hours, to assess serum iron level, in order to measure the area under the curve of iron kinetic.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Decrease of post-prandial iron absorption after dietary polyphenol supplementation
Time Frame: at day 3
decrease of intestinal iron absorption after standardized oral loading dose through rich-iron meal, expressed by area-under-the-curve of serum iron, due to concomitant administration of a single dose of dietary polyphenos (nutrient complement) versus placebo administration. This outcome is a quantitative variable, treated and analysed as such.
at day 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-prandial changes of circulating oxylipin in iron overload diseases after iron-rich meal and effects of polyphenols supplementation
Time Frame: at day 1 (fasting versus 3 hours after rich-iron meal, versus 3 hours after rich-iron meal with polyphenol supplementation)
comparison of oxylipin levels, through lipidomic analyses by spectrophotometry
at day 1 (fasting versus 3 hours after rich-iron meal, versus 3 hours after rich-iron meal with polyphenol supplementation)
Comparison of oxylipin levels between DIOS, genetic hemochromatosis and healthy subjects after 6 hours of fasting.
Time Frame: at baseline
comparison of oxylipin levels, through lipidomic analyses by spectrophotometry. Healthy subjects datas comes from a previous study (MEPHISTO).
at baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Clermont-Ferrand

Investigators

  • Principal Investigator: Marc RUIVARD, University Hospital, Clermont-Ferrand

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 9, 2018

Primary Completion (Actual)

July 20, 2018

Study Completion (Actual)

July 20, 2018

Study Registration Dates

First Submitted

February 27, 2018

First Submitted That Met QC Criteria

February 27, 2018

First Posted (Actual)

March 5, 2018

Study Record Updates

Last Update Posted (Actual)

April 1, 2019

Last Update Submitted That Met QC Criteria

March 29, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHU-381
  • 2017-A01955-48 (Other Identifier: 2017-A01955-48)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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