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

NCT05326503 | Completed

• 1 other identifier: Fe-PP-Thal
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Thalassemia; Iron Overload

Keywords

Iron overload; Thalassemia; Polyphenols; Iron absorption

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Serum ferritin (µg/L)

  At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)

• Soluble transferrin receptor (mg/L)

  At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)

• Transferrin saturation (%)

  At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)

• Hemoglobin (g/dL)

  At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)

• C-reactive protein (mg/L)

  At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)

Study Arms (4)

Meal with polyphenol supplement (PPS)

EXPERIMENTAL

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)

Meal with placebo

PLACEBO COMPARATOR

Iron-rich test meal labelled with stable iron isotope as ferrous sulfate, consumed with placebo supplement (maltodextrin).

Dietary Supplement: Meal matrix with placebo

Drink with PPS

EXPERIMENTAL

Iron-fortified drink labelled with stable iron isotope as ferrous sulfate, consumed with the polyphenol supplement.

Dietary Supplement: No meal matrix with PPS

Drink with placebo

PLACEBO COMPARATOR

Iron-fortified drink labelled with stable iron isotope as ferrous sulfate, consumed with placebo supplement (maltodextrin).

Dietary Supplement: No meal matrix with placebo

Interventions

Meal matrix with polyphenol supplement (PPS) DIETARY_SUPPLEMENT

Test meal with polyphenol supplement

Meal with polyphenol supplement (PPS)

Meal matrix with placebo DIETARY_SUPPLEMENT

Test meal with placebo (maltodextrin) supplement

Meal with placebo

No meal matrix with PPS DIETARY_SUPPLEMENT

Test drink with polyphenol supplement

Drink with PPS

No meal matrix with placebo DIETARY_SUPPLEMENT

Test drink with placebo (maltodextrin) supplement

Drink with placebo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

Sponsors & Collaborators

• Swiss Federal Institute of Technology: lead
• Mahidol University: collaborator

Study Sites (1)

Mahidol University

Salaya, Thailand

Location

MeSH Terms

Conditions

Thalassemia; Iron Overload

Interventions

Pentosan Sulfuric Polyester

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Organic Chemicals; Polysaccharides; Carbohydrates

Study Officials

• Michael B Zimmermann, MD, PhD

  ETH Zurich

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: April 13, 2022
• Study Start: June 1, 2022
• Primary Completion: September 11, 2023
• Study Completion: September 11, 2023
• Last Updated: March 5, 2025

Record last verified: 2025-02

Locations

TH (1)