POLYFER: Effects of Polyphenols on Iron Absorption in Iron Overload Disorders.

Sponsor

University Hospital, Clermont-Ferrand (Other)

Overall Status

Completed

CT.gov ID

NCT03453918

Collaborator

(none)

Enrollment

Location

Arms

3.4

Actual Duration (Months)

12.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dysmetabolic Iron Overload Syndrome Genetic Hemochromatosis Iron Absorption Polyphenols	Dietary Supplement: polyphenols Other: Placebo	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

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

Primary Purpose:

Prevention

Official Title:

Effects of Polyphenols on Iron Absorption in Iron Overload Disorders.

Actual Study Start Date :

Apr 9, 2018

Actual Primary Completion Date :

Jul 20, 2018

Actual Study Completion Date :

Jul 20, 2018

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

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

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.