Effects of Polyphenols on Iron Absorption in Iron Overload Disorders.

Not Applicable

Completed

• Conditions: Genetic Hemochromatosis; Iron Absorption; Dysmetabolic Iron Overload Syndrome; Polyphenols
• Interventions: Dietary Supplement: polyphenols; Other: Placebo

• Registration Number: NCT03453918
• Lead Sponsor: University Hospital, Clermont-Ferrand

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-02-27
• Study First Submitted QC: 2018-02-27
• Study First Posted: 2018-03-05
• Study Start: 2018-04-09
• Primary Completion: 2018-07-20
• Study Completion: 2018-07-20
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-29
• Last Update Posted: 2019-04-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Polyphenols	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.
Placebo	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.

Primary Outcome Measures

Name	Time	Method
Decrease of post-prandial iron absorption after dietary polyphenol supplementation	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.

Secondary Outcome Measures

Name	Time	Method
Post-prandial changes of circulating oxylipin in iron overload diseases after iron-rich meal and effects of polyphenols supplementation	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
Comparison of oxylipin levels between DIOS, genetic hemochromatosis and healthy subjects after 6 hours of fasting.	at baseline	comparison of oxylipin levels, through lipidomic analyses by spectrophotometry. Healthy subjects datas comes from a previous study (MEPHISTO).

Trial Locations

Locations (1)

CHU Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France