Inhibitory Effect of a Polyphenol Supplement on Dietary Iron Absorption in Adults With Thalassemia

Study Overview
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Brief Summary
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Genetic disorders, such as thalassemia, can lead to iron overload and severe adverse health outcomes. In iron-loading thalassemia, iron overload is due to increased iron absorption. Iron accumulates in the body organs causing widespread damage. The standard treatment is iron chelation therapy and/or periodic phlebotomy to remove iron from the body; frequency of phlebotomy or chelation therapy is dependent on how quickly body iron stores accumulate. Polyphenolic compounds are very strong inhibitors of non-heme iron absorption, as they form insoluble complexes with ferrous iron in the gastrointestinal tract that cannot be absorbed. The investigators have recently shown in European subjects with hereditary hemochromatosis (another iron-loading disorder) that our newly-developed natural polyphenol supplement (PPS) that is rich in polyphenols, when taken with iron-rich meals or with an iron-fortified drink, reduces iron absorption by  40%. Decreasing non-heme iron absorption in adults with iron-loading thalassemia could potentially lead to an extension of the time period between phlebotomies or chelation therapies, and therefore an improved quality of life. Therefore, in this stable iron isotope study, the investigators will study the effect the natural PPS on oral iron absorption from an iron-rich test meal or iron-fortified drink in Thai adults with iron-loading thalassemia.

Official Title
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Testing a Natural Polyphenol Supplement to Inhibit Dietary Iron Absorption in Thai Adults With Iron-loading Thalassemia: a Stable Isotope Study

Conditions
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Thalassemia, Iron Overload

Intervention / Treatment
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* Dietary Supplement: Meal matrix with polyphenol supplement (PPS)
* Dietary Supplement: Meal matrix with placebo
* Dietary Supplement: No meal matrix with PPS
* Dietary Supplement: No meal matrix with placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of thalassemia minor or intermedia (β-thalassemia with or without α-globin gene mutations, Hb E/β-thalassemia with or without α-globin gene mutations, or α-thalassemia Hb H disease) based on Hb electrophoresis/HPLC and/or DNA analysis from the subject's medical record. Hemoglobin (Hb): 7.0-13.5 g/dL for males; 7.0-12.0 for females Serum ferritin (SF): 300-800 ug/L for males; 200-800 ug/L for females Not having had a blood transfusion within 6 months prior to the study start Age 18-49 y, not pregnant or lactating Body weight <75 kg and body mass index (BMI) between 17 and 25 kg/m2 No acute illness/infection (self-reported) No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) No scheduled phlebotomy or blood transfusion during the study period The last phlebotomy will be at least 4 weeks prior to first study visit No intake of iron chelators 4 weeks prior to first study visit and throughout the study period No use of medications affecting iron absorption or metabolism during the study No intake of mineral/vitamin supplements 2 weeks prior to the first study visit and during the study No participation in any other clinical study within the last 30 days and during the study Expected to comply with study protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Meal with polyphenol supplement (PPS)<br>Iron-rich test meal labelled with stable iron isotope as ferrous sulfate, consumed with the polyphenol supplement. | Dietary Supplement: Meal matrix with polyphenol supplement (PPS)<br>* Test meal with polyphenol supplement<br>|
| Placebo Comparator: Meal with placebo<br>Iron-rich test meal labelled with stable iron isotope as ferrous sulfate, consumed with placebo supplement (maltodextrin). | Dietary Supplement: Meal matrix with placebo<br>* Test meal with placebo (maltodextrin) supplement<br>|
| Experimental: Drink with PPS<br>Iron-fortified drink labelled with stable iron isotope as ferrous sulfate, consumed with the polyphenol supplement. | Dietary Supplement: No meal matrix with PPS<br>* Test drink with polyphenol supplement<br>|
| Placebo Comparator: Drink with placebo<br>Iron-fortified drink labelled with stable iron isotope as ferrous sulfate, consumed with placebo supplement (maltodextrin). | Dietary Supplement: No meal matrix with placebo<br>* Test drink with placebo (maltodextrin) supplement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in fractional iron absorption (FIA) from iron-rich test meal administered with and without the polyphenol supplement (PPS). | FIA from labelled test meals consumed with the PPS and consumed with the placebo will be determined based on the shift of the iron isotope ratios in whole blood. | Measured 14 days after administration of last test meal (study day 18 or 35) | 
| Difference in FIA from iron-fortified test drink administered with and without the PPS. | FIA from labelled test drink consumed with the PPS and consumed with the placebo will be determined based on the shift of the iron isotope ratios in whole blood. | Measured 14 days after administration of last test drink (study day 18 or 35) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum ferritin (µg/L) | to assess iron status | At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35) | 
| Soluble transferrin receptor (mg/L) | to assess iron status | At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35) | 
| Transferrin saturation (%) | to assess iron status | At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35) | 
| Hemoglobin (g/dL) | to identify anemia and to determine blood volume | At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35) | 
| C-reactive protein (mg/L) | To assess inflammation status | At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35) | 
| Alpha-1-glycoprotein (g/L), | To assess inflammation status | At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35) | 
| Serum hepcidin (nM) | Major regulator of non-heme iron absorption | At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thalassemia, Iron overload, Polyphenols, Iron absorption