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The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study

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ClinicalTrials.gov Identifier: NCT03317873
Recruitment Status : Completed
First Posted : October 23, 2017
Last Update Posted : June 12, 2019
Sponsor:
Collaborator:
Chang Gung Memorial Hospital
Information provided by (Responsible Party):
Swiss Federal Institute of Technology

Tracking Information
First Submitted Date  ICMJE October 18, 2017
First Posted Date  ICMJE October 23, 2017
Last Update Posted Date June 12, 2019
Actual Study Start Date  ICMJE November 1, 2017
Actual Primary Completion Date February 19, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2017)
Change from baseline in the isotopic ratio of iron in blood at week 2 [ Time Frame: baseline, 2 weeks ]
The change in the isotopic ratio of iron in blood will be measured after the administration of test meal including iron isotopes.
Original Primary Outcome Measures  ICMJE
 (submitted: October 18, 2017)
fractional iron absorption [ Time Frame: baseline, 2 weeks ]
The difference in oral iron absorption from a test meal comparing young women with AA versus VV variants of SNP rs855791
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2017)
  • hepcidin [ Time Frame: baseline ]
    fasting concentrations of plasma hepcidin in AA and VV variants of SNP rs855791
  • iron status [ Time Frame: baseline ]
    The difference in fasting concentrations of serum iron, transferrin saturation, serum ferritin, hemoglobin, erythrocyte volume in AA and VV variants of SNP rs855791
Original Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2017)
hepcidin and iron status [ Time Frame: baseline ]
• The difference in fasting concentrations of plasma hepcidin, serum iron, transferrin saturation, serum ferritin, hemoglobin, erythrocyte volume comparing AA versus VV variants of SNP rs855791
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study
Official Title  ICMJE The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Condition  ICMJE Iron Metabolism Disorders
Intervention  ICMJE
  • Dietary Supplement: Testmeal A
    The tesmeal A is is plain rice, with a seaweed sauce, fortified with labelled iron as stable iron isotope as ferrous sulfate
  • Dietary Supplement: Testmeal B
    The tesmeal B is plain rice, with a seaweed sauce, fortified with labelled iron as stable iron isotope as ferrous sulfate
Study Arms  ICMJE
  • Experimental: wild type AA (CC)
    All participants with the wild type genotype AA (CC) will be allocated to this group
    Interventions:
    • Dietary Supplement: Testmeal A
    • Dietary Supplement: Testmeal B
  • Experimental: mutation VV (TT)
    All participants with the mutation genotype VV (TT) will be allocated to this group
    Interventions:
    • Dietary Supplement: Testmeal A
    • Dietary Supplement: Testmeal B
Publications * 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. 2020 Oct 5;Online ahead of print. doi: 10.3324/haematol.2020.264556.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 18, 2017)
80
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 19, 2019
Actual Primary Completion Date February 19, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 20 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03317873
Other Study ID Numbers  ICMJE TMPRSS6_Fe
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Swiss Federal Institute of Technology
Study Sponsor  ICMJE Swiss Federal Institute of Technology
Collaborators  ICMJE Chang Gung Memorial Hospital
Investigators  ICMJE Not Provided
PRS Account Swiss Federal Institute of Technology
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP