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Trial record 79 of 7708 for:    Area Under Curve

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

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ClinicalTrials.gov Identifier: NCT03453918
Recruitment Status : Completed
First Posted : March 5, 2018
Last Update Posted : April 1, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Dysmetabolic Iron Overload Syndrome Genetic Hemochromatosis Iron Absorption Polyphenols Dietary Supplement: polyphenols Other: Placebo Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
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 : April 9, 2018
Actual Primary Completion Date : July 20, 2018
Actual Study Completion Date : July 20, 2018


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.





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03453918


Locations
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France
CHU Clermont-Ferrand
Clermont-Ferrand, France, 63003
Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Investigators
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Principal Investigator: Marc RUIVARD University Hospital, Clermont-Ferrand

Additional Information:
Publications:

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Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT03453918     History of Changes
Other Study ID Numbers: CHU-381
2017-A01955-48 ( Other Identifier: 2017-A01955-48 )
First Posted: March 5, 2018    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Clermont-Ferrand:
Iron absorption
Polyphenols
Dysmetabolic iron overload syndrome
Metabolic syndrome X
Genetic Hemochromatosis
Oxylipin
Lipidomic analysis
Additional relevant MeSH terms:
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Hemochromatosis
Iron Overload
Syndrome
Disease
Pathologic Processes
Iron Metabolism Disorders
Metabolic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Iron
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs