Clinical trial NCT05326503: Inhibitory Effect of a Polyphenol Supplement on Dietary Iron Absorption in Adults with Thalassemia
Official title: Testing a Natural Polyphenol Supplement to Inhibit Dietary Iron Absorption in Thai Adults with Iron-loading Thalassemia: a Stable Isotope Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Thalassemia
Iron Overload
Keywords: Iron overload
Thalassemia
Polyphenols
Iron absorption
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
Collaborators: name: Mahidol University
First posted: 2022-04-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Difference in fractional iron absorption (FIA) from iron-rich test meal administered with and without the polyphenol supplement (PPS).
timeFrame: Measured 14 days after administration of last test meal (study day 18 or 35)
measure: Difference in FIA from iron-fortified test drink administered with and without the PPS.
timeFrame: Measured 14 days after administration of last test drink (study day 18 or 35)
Secondary outcomes:
measure: Serum ferritin (µg/L)
timeFrame: At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)
measure: Soluble transferrin receptor (mg/L)
timeFrame: At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)
measure: Transferrin saturation (%)
timeFrame: At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)
measure: Hemoglobin (g/dL)
timeFrame: At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)
measure: C-reactive protein (mg/L)
timeFrame: At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)
measure: Alpha-1-glycoprotein (g/L),
timeFrame: At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)
measure: Serum hepcidin (nM)
timeFrame: At baseline (study day 1), midpoint (study day 18), and endpoint (study day 35)
Other outcomes:
Locations:
city: Salaya
country: Thailand
facility: Mahidol University
Study officials:
affiliation: ETH Zurich
name: Michael B Zimmermann, MD, PhD
role: STUDY_DIRECTOR
References: