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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03453918
Other study ID # CHU-381
Secondary ID 2017-A01955-48
Status Completed
Phase N/A
First received
Last updated
Start date April 9, 2018
Est. completion date July 20, 2018

Study information

Verified date March 2019
Source University Hospital, Clermont-Ferrand
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 41
Est. completion date July 20, 2018
Est. primary completion date July 20, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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


Related Conditions & MeSH terms


Intervention

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.
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.

Locations

Country Name City State
France CHU Clermont-Ferrand Clermont-Ferrand

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

References & Publications (35)

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Hoppe M, Hulthén L. Validation of the clinical approach of using the induced serum iron increase after 1h as a measure of iron absorption. Clin Nutr. 2006 Feb;25(1):163-5. Epub 2005 Nov 22. — View Citation

Hurrell RF, Reddy M, Cook JD. Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br J Nutr. 1999 Apr;81(4):289-95. — View Citation

Jouanolle AM, Fergelot P, Gandon G, Yaouanq J, Le Gall JY, David V. A candidate gene for hemochromatosis: frequency of the C282Y and H63D mutations. Hum Genet. 1997 Oct;100(5-6):544-7. — View Citation

Kim J, Carlson ME, Kuchel GA, Newman JW, Watkins BA. Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression and epididymal fat mass while improving aspects of glucose use in muscle in C57BL/6J mice. Int J Obes (Lond). 2016 Jan;40(1):129-37. doi: 10.1038/ijo.2015.135. Epub 2015 Jul 29. — View Citation

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Kobune M, Miyanishi K, Takada K, Kawano Y, Nagashima H, Kikuchi S, Murase K, Iyama S, Sato T, Sato Y, Takimoto R, Kato J. Establishment of a simple test for iron absorption from the gastrointestinal tract. Int J Hematol. 2011 Jun;93(6):715-719. doi: 10.1007/s12185-011-0878-8. Epub 2011 Jun 1. — View Citation

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Ruivard M, Feillet-Coudray C, Rambeau M, Gerbaud L, Mazur A, Rayssiguier Y, Philippe P, Coudray C. Effect of daily versus twice weekly long-term iron supplementation on iron absorption and status in iron-deficient women: a stable isotope study. Clin Biochem. 2006 Jul;39(7):700-7. Epub 2006 Apr 5. — View Citation

Ruivard M, Lainé F, Ganz T, Olbina G, Westerman M, Nemeth E, Rambeau M, Mazur A, Gerbaud L, Tournilhac V, Abergel A, Philippe P, Deugnier Y, Coudray C. Iron absorption in dysmetabolic iron overload syndrome is decreased and correlates with increased plasma hepcidin. J Hepatol. 2009 Jun;50(6):1219-25. doi: 10.1016/j.jhep.2009.01.029. Epub 2009 Apr 5. — View Citation

Sjödin P, Wallin H, Alexander J, Jägerstad M. Disposition and metabolism of the food mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in rats. Carcinogenesis. 1989 Jul;10(7):1269-75. — View Citation

Tako E, Beebe SE, Reed S, Hart JJ, Glahn RP. Polyphenolic compounds appear to limit the nutritional benefit of biofortified higher iron black bean (Phaseolus vulgaris L.). Nutr J. 2014 Mar 26;13:28. doi: 10.1186/1475-2891-13-28. — View Citation

Tako E, Reed SM, Budiman J, Hart JJ, Glahn RP. Higher iron pearl millet (Pennisetum glaucum L.) provides more absorbable iron that is limited by increased polyphenolic content. Nutr J. 2015 Jan 23;14:11. doi: 10.1186/1475-2891-14-11. — View Citation

Tondeur MC, Schauer CS, Christofides AL, Asante KP, Newton S, Serfass RE, Zlotkin SH. Determination of iron absorption from intrinsically labeled microencapsulated ferrous fumarate (sprinkles) in infants with different iron and hematologic status by using a dual-stable-isotope method. Am J Clin Nutr. 2004 Nov;80(5):1436-44. — View Citation

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* Note: There are 35 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Decrease of post-prandial iron absorption after dietary polyphenol supplementation 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 Post-prandial changes of circulating oxylipin in iron overload diseases after iron-rich meal and effects of polyphenols 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)
Secondary Comparison of oxylipin levels between DIOS, genetic hemochromatosis and healthy subjects after 6 hours of fasting. comparison of oxylipin levels, through lipidomic analyses by spectrophotometry. Healthy subjects datas comes from a previous study (MEPHISTO). at baseline
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