The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study
Primary Purpose
Iron Metabolism Disorders
Status
Completed
Phase
Not Applicable
Locations
Taiwan
Study Type
Interventional
Intervention
Testmeal A
Testmeal B
Sponsored by
About this trial
This is an interventional prevention trial for Iron Metabolism Disorders
Eligibility Criteria
Inclusion Criteria:
- Subjects homozygotous for the for AA (CC), or VV (TT) variant of the SNP rs855791 of the TMPRSS6 gene.
- Females 20 - 45 years of age (premenopausal status)
- obtained informed consent
- regular menstrual cycle, ± 2 days
Exclusion Criteria:
- Pregnancy or lactating (assessed by pregnancy test and self-declaration, respectively)
- Anemia defined as Hb < 120 g/L
- Plasma ferritin < 30 µg/l, or > 120 µg/l
- C-reactive Protein > 5 mg/l
- Body weight > 65 kg
- Body mass index (BMI) 18.5 - 25
- Diagnosed metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal.
- Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 6 months, prior the first study day.
- Subjects who cannot be expected to comply with study protocol (e.g. non-residents).
- Use of long-term medication during the study
- Subjects that will take part of another clinical study at the same time or had within the last 30 days before the first study day
- Intake of mineral/vitamin supplements 2 weeks before the first study day and during the study
Sites / Locations
- Kaohsiung-Chang Gun Memorial Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
wild type AA (CC)
mutation VV (TT)
Arm Description
All participants with the wild type genotype AA (CC) will be allocated to this group
All participants with the mutation genotype VV (TT) will be allocated to this group
Outcomes
Primary Outcome Measures
Change from baseline in the isotopic ratio of iron in blood at week 2
The change in the isotopic ratio of iron in blood will be measured after the administration of test meal including iron isotopes.
Secondary Outcome Measures
hepcidin
fasting concentrations of plasma hepcidin in AA and VV variants of SNP rs855791
iron status
The difference in fasting concentrations of serum iron, transferrin saturation, serum ferritin, hemoglobin, erythrocyte volume in AA and VV variants of SNP rs855791
Full Information
NCT ID
NCT03317873
First Posted
October 18, 2017
Last Updated
June 11, 2019
Sponsor
Swiss Federal Institute of Technology
Collaborators
Chang Gung Memorial Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03317873
Brief Title
The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study
Official Title
The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
February 19, 2019 (Actual)
Study Completion Date
February 19, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Federal Institute of Technology
Collaborators
Chang Gung Memorial Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Iron deficiency is considered the most common nutritional deficiency worldwide and affects children and women in both non-industrialized as well as industrialized countries. The main regulatory molecule of iron metabolism is hepcidin, a hormone produced in the liver that regulates intestinal iron absorption, placental transport, recycling of iron by macrophages and release from stores. The expression of hepcidin is regulated by many mediators, one of which is Matriptase-2 - a transmembrane protease. Complete loss of function leads to the rare disease iron-refractory iron deficiency anemia (IRIDA). Matriptase-2 is encoded by the gene TMPRSS6 and the single nucleotide polymorphism (SNP) rs855791 causes a non-synonymous substitution (V736A) that reduces the activity of the protease to inhibit hepcidin transcription. Genome wide association studies have identified the TMPRSS6 SNP rs855791 has a strong association with red blood cell and iron parameters in the general population.
The objectives of the study is to measure oral iron absorption and systemic iron utilization into red blood cells (RBC) using oral isotopic labels in subjects homozygotes for common variants of the TMPRSS6 gene with the SNP rs855791 (A736V); AA vs. VV subjects.
The aim is to conduct an iron absorption study in 80 Taiwanese women of reproductive age, non-pregnant, non-anemic, investigating the effect of the genetic variants of the SNP rs855791. The participants will be split in two groups of equal size; wild type AA vs. mutation VV. Iron absorption and systemic utilization will be assessed by two test meals containing stable isotopes of iron.The primary outcome of the trial is the oral iron absorption from a test meal as compared between the two genotypes AA vs. VV. Secondary outcomes are the comparison iron status markers between the two genotypes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron Metabolism Disorders
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
wild type AA (CC)
Arm Type
Experimental
Arm Description
All participants with the wild type genotype AA (CC) will be allocated to this group
Arm Title
mutation VV (TT)
Arm Type
Experimental
Arm Description
All participants with the mutation genotype VV (TT) will be allocated to this group
Intervention Type
Dietary Supplement
Intervention Name(s)
Testmeal A
Intervention Description
The tesmeal A is is plain rice, with a seaweed sauce, fortified with labelled iron as stable iron isotope as ferrous sulfate
Intervention Type
Dietary Supplement
Intervention Name(s)
Testmeal B
Intervention Description
The tesmeal B is plain rice, with a seaweed sauce, fortified with labelled iron as stable iron isotope as ferrous sulfate
Primary Outcome Measure Information:
Title
Change from baseline in the isotopic ratio of iron in blood at week 2
Description
The change in the isotopic ratio of iron in blood will be measured after the administration of test meal including iron isotopes.
Time Frame
baseline, 2 weeks
Secondary Outcome Measure Information:
Title
hepcidin
Description
fasting concentrations of plasma hepcidin in AA and VV variants of SNP rs855791
Time Frame
baseline
Title
iron status
Description
The difference in fasting concentrations of serum iron, transferrin saturation, serum ferritin, hemoglobin, erythrocyte volume in AA and VV variants of SNP rs855791
Time Frame
baseline
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subjects homozygotous for the for AA (CC), or VV (TT) variant of the SNP rs855791 of the TMPRSS6 gene.
Females 20 - 45 years of age (premenopausal status)
obtained informed consent
regular menstrual cycle, ± 2 days
Exclusion Criteria:
Pregnancy or lactating (assessed by pregnancy test and self-declaration, respectively)
Anemia defined as Hb < 120 g/L
Plasma ferritin < 30 µg/l, or > 120 µg/l
C-reactive Protein > 5 mg/l
Body weight > 65 kg
Body mass index (BMI) 18.5 - 25
Diagnosed metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal.
Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 6 months, prior the first study day.
Subjects who cannot be expected to comply with study protocol (e.g. non-residents).
Use of long-term medication during the study
Subjects that will take part of another clinical study at the same time or had within the last 30 days before the first study day
Intake of mineral/vitamin supplements 2 weeks before the first study day and during the study
Facility Information:
Facility Name
Kaohsiung-Chang Gun Memorial Hospital
City
Kaohsiung City
State/Province
Kaohsiung
ZIP/Postal Code
83301
Country
Taiwan
12. IPD Sharing Statement
Citations:
PubMed Identifier
33054130
Citation
Buerkli S, Pei SN, Hsiao SC, Lee CT, Zeder C, Zimmermann MB, Moretti D. The <em>TMPRSS6</em> variant (SNP rs855791) affects iron metabolism and oral iron absorption - a stable iron isotope study in Taiwanese women. Haematologica. 2021 Nov 1;106(11):2897-2905. doi: 10.3324/haematol.2020.264556.
Results Reference
derived
Learn more about this trial
The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study
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