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

Sponsor

Swiss Federal Institute of Technology (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05326503

Collaborator

Mahidol University (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Thalassemia Iron Overload	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	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Participant)

Primary Purpose:

Supportive Care

Official Title:

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

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Difference in fractional iron absorption (FIA) from iron-rich test meal administered with and without the polyphenol supplement (PPS). [Measured 14 days after administration of last test meal (study day 18 or 35)]
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.
Difference in FIA from iron-fortified test drink administered with and without the PPS. [Measured 14 days after administration of last test drink (study day 18 or 35)]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 49 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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