4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Potential Harms of Untargeted Iron Supplementation in Cambodia Where Iron Deficiency is Not the Cause of Anemia

Potential Harms of Untargeted Iron Supplementation in Cambodia Where Iron Deficiency is Not the Cause of Anemia

Study Description
Brief Summary:

In 2016, the World Health Organization (WHO) set a global policy recommending daily oral iron supplementation (60 mg iron) for 12 weeks for all women living in countries where anemia prevalence is >40%, such as in Cambodia. However, recent studies have shown the prevalence of iron deficiency to be low in Cambodian women and that supplementation would likely only benefit ~10% of women.

Iron supplementation may be harmful in women with genetic blood disorders (e.g. thalassemia), which are common in Cambodia, as these individuals are already at an increased risk of iron overload. The risks are made greater by the fact that iron absorption from most common form of supplementation, ferrous sulfate, is low. Typically less than 20% is absorbed in the gut; the remaining 80% passes unabsorbed into the colon where it can increase the risk of pathogen growth and gut inflammation. Alternatively, ferrous bisglycinate is a newer supplemental form of iron. This amino acid chelate has 2-4x higher bioavailability than ferrous sulfate and is associated with fewer GI side-effects.

In view of WHO policy and risks of supplementation, there is a need to determine the potential for harm, and if novel forms of iron supplements are safer.


Condition or disease Intervention/treatment Phase
Anemia, Iron Deficiency Anemia Intestinal Inflammation Inflammation Intestine; Complaints Dietary Supplement: Ferrous sulfate Dietary Supplement: Ferrous Bisglycinate Dietary Supplement: Placebo of microcrystalline cellulose Phase 4

Detailed Description:

The World Health Organization (WHO) set a Global Nutrition Target to reduce anemia in women of reproductive age by 50% by 2025. In 2016, the WHO implemented a global policy recommending oral iron supplementation (60 mg daily for 12 weeks) for all women where anemia prevalence is more than 40%, such as in Cambodia.

However, recent studies have shown the prevalence of iron deficiency to be low in Cambodian women. If iron deficiency is not the cause of anemia, then iron supplementation will not be effective at treating it. Further, iron supplementation may be harmful in some individuals, especially those with anemia caused by genetic blood disorders (which are common in Cambodia), as these individuals are already at an increased risk of iron overload. The risks are made greater by the fact that the type of iron that is commonly used in supplements (ferrous sulfate) is poorly absorbed. Typically, less than 20% is absorbed in the gut; the remaining 80% is unabsorbed in the colon where it can increase the risk of pathogen growth and gut inflammation.

To investigate the safety of untargeted iron supplementation, we will undertake a new study in Cambodia, where we will evaluate a newer type of iron supplement that may be absorbed better, and thus, safer than the conventional type. We will recruit non-pregnant women (18-45 years) and ask them to take one of the two forms of iron (ferrous sulfate or ferrous bisglycinate) or a placebo for 12 weeks (in line with the WHO global policy). We will measure hemoglobin and ferritin levels, which are markers of anemia and iron status, and markers of gut inflammation and gut pathogen abundance, before and after the intervention. This study will contribute to the evidence for safe and effective iron supplementation for women worldwide.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 480 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 12-week double-blind, three-arm, placebo-controlled randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The manufacturers of the tablets (Dr. Simon Wood, Natural Factors) will be responsible for allocation concealment of the three tablet formulations at time of packaging. All tablets will be non-distinguishable in size, colour, and packaging. Trial investigators, research staff, and participants will all be blinded to the assigned interventions
Primary Purpose: Treatment
Official Title: Is Iron Supplementation Harmful in Populations Where Iron Deficiency is Not the Cause of Anemia? A 12 Week Randomized Controlled Trial in Cambodia
Actual Study Start Date : December 10, 2019
Actual Primary Completion Date : May 30, 2020
Estimated Study Completion Date : March 2022
Arms and Interventions
Arm Intervention/treatment
Active Comparator: Ferrous Sulfate
Iron will be given orally in the form of tablets. A supplement of 60 mg will be taken daily for 12 weeks. World Health Organization standard dose and commonly used form of iron.
 Dietary Supplement: Ferrous sulfate
60 mg elemental iron as ferrous sulfate
Other Names:
  • iron sulfate
  • ferrous sulphate
  • iron sulphate
  • Iron(II) sulfate
Experimental: Ferrous Bisglycinate
Iron will be given orally in the form of tablets. A supplement of 18 mg will be taken daily for 12 weeks. Ferrous bisglycinate has a bioavailability 2-4x greater than ferrous sulfate.
 Dietary Supplement: Ferrous Bisglycinate
18 mg elemental iron as ferrous bisglycinate
Other Names:
  • iron amino acid chelate
  • Iron glycinate
  • Bisglycine iron(II) salt
  • Iron(II) bisglycinate
  • Ferrous Bis-glycinate
Placebo Comparator: Placebo
Placebo will be given orally in the form of tablets as a control made of microcrystalline cellulose.
 Dietary Supplement: Placebo of microcrystalline cellulose
placebo
Other Name: Control
Outcome Measures
Primary Outcome Measures :
  1. Serum Ferritin [ Time Frame: 12 weeks ]
    Serum ferritin concentration (µg/l) at 12 weeks

  2. Fecal calprotectin [ Time Frame: 12 weeks ]
    Fecal calprotectin concentration (mg/kg stool) at 12 weeks as a measure of gut inflammation.


Secondary Outcome Measures :
  1. Gut pathogen abundance [ Time Frame: 12 weeks ]
    Real-time PCR nucleic acid amplification assay with an enteric bacterial panel.

  2. Gut parasite abundance [ Time Frame: 12 weeks ]
    Real-time PCR nucleic acid amplification assay with an enteric parasite panel.

  3. DNA damage [ Time Frame: 12 weeks ]
    DNA damage will be assessed by measuring DNA single-strand breaks, indicated by olive tail movement with use of alkali single-cell gel electrophoresis (Comet assay).

  4. Alpha-1 acid glycoprotein (AGP, g/l) [ Time Frame: 12 weeks ]
  5. C-reactive protein (CRP, mg/l) [ Time Frame: 12 weeks ]
  6. Hemoglobin (g/L) [ Time Frame: 12 weeks ]
  7. Folate (ng/ml) [ Time Frame: 12 weeks ]
  8. Vitamin B12 (pmol/l) [ Time Frame: 12 weeks ]

Other Outcome Measures:
  1. Reported side effects [ Time Frame: Continuous over 12 weeks ]
    (e.g., gastrointestinal pain) as a quality of life measure.

  2. Genetic hemoglobinopathies [ Time Frame: Baseline ]
    Genotyping to detect the presence of the most common hemoglobinopathies

  3. Gut Pathogen abundance [ Time Frame: 12 weeks ]
    Whole metagenome shotgun 16S ribosomal RNA sequencing will be conducted on fecal samples, in order to validate the method against the established BD MAX panel in a subset of 150 women from our trial (50 from each study arm).


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • apparently healthy
  • consent to participate in the study and provide blood, flocked rectal swab and stool samples
  • expected to reside in the study location for the study period.

Exclusion Criteria:

  • any known illness or disease
  • pregnant
  • taking antibiotics, non-steroidal anti-inflammatory drugs, dietary supplements, or vitamin and mineral supplements in the previous 12 weeks.
Contacts and Locations

Locations
Layout table for location information
Cambodia
Prey Kuy, Srayov and Tboung Krapeu Health Centres
Kampong Thom, Cambodia
Sponsors and Collaborators
University of British Columbia
Helen Keller International
NCHADS - Ministry of Health of Cambodia
BC Children's Hospital Research Institute
The National Institute of Public Health Laboratory, Phnom Penh
Tracking Information
First Submitted Date  ICMJE July 4, 2019
First Posted Date  ICMJE July 12, 2019
Last Update Posted Date April 28, 2021
Actual Study Start Date  ICMJE December 10, 2019
Actual Primary Completion Date May 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
  • Serum Ferritin [ Time Frame: 12 weeks ]
    Serum ferritin concentration (µg/l) at 12 weeks
  • Fecal calprotectin [ Time Frame: 12 weeks ]
    Fecal calprotectin concentration (mg/kg stool) at 12 weeks as a measure of gut inflammation.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
  • Gut pathogen abundance [ Time Frame: 12 weeks ]
    Real-time PCR nucleic acid amplification assay with an enteric bacterial panel.
  • Gut parasite abundance [ Time Frame: 12 weeks ]
    Real-time PCR nucleic acid amplification assay with an enteric parasite panel.
  • DNA damage [ Time Frame: 12 weeks ]
    DNA damage will be assessed by measuring DNA single-strand breaks, indicated by olive tail movement with use of alkali single-cell gel electrophoresis (Comet assay).
  • Alpha-1 acid glycoprotein (AGP, g/l) [ Time Frame: 12 weeks ]
  • C-reactive protein (CRP, mg/l) [ Time Frame: 12 weeks ]
  • Hemoglobin (g/L) [ Time Frame: 12 weeks ]
  • Folate (ng/ml) [ Time Frame: 12 weeks ]
  • Vitamin B12 (pmol/l) [ Time Frame: 12 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 10, 2019)
  • Reported side effects [ Time Frame: Continuous over 12 weeks ]
    (e.g., gastrointestinal pain) as a quality of life measure.
  • Genetic hemoglobinopathies [ Time Frame: Baseline ]
    Genotyping to detect the presence of the most common hemoglobinopathies
  • Gut Pathogen abundance [ Time Frame: 12 weeks ]
    Whole metagenome shotgun 16S ribosomal RNA sequencing will be conducted on fecal samples, in order to validate the method against the established BD MAX panel in a subset of 150 women from our trial (50 from each study arm).
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Potential Harms of Untargeted Iron Supplementation in Cambodia Where Iron Deficiency is Not the Cause of Anemia
Official Title  ICMJE Is Iron Supplementation Harmful in Populations Where Iron Deficiency is Not the Cause of Anemia? A 12 Week Randomized Controlled Trial in Cambodia
Brief Summary

In 2016, the World Health Organization (WHO) set a global policy recommending daily oral iron supplementation (60 mg iron) for 12 weeks for all women living in countries where anemia prevalence is >40%, such as in Cambodia. However, recent studies have shown the prevalence of iron deficiency to be low in Cambodian women and that supplementation would likely only benefit ~10% of women.

Iron supplementation may be harmful in women with genetic blood disorders (e.g. thalassemia), which are common in Cambodia, as these individuals are already at an increased risk of iron overload. The risks are made greater by the fact that iron absorption from most common form of supplementation, ferrous sulfate, is low. Typically less than 20% is absorbed in the gut; the remaining 80% passes unabsorbed into the colon where it can increase the risk of pathogen growth and gut inflammation. Alternatively, ferrous bisglycinate is a newer supplemental form of iron. This amino acid chelate has 2-4x higher bioavailability than ferrous sulfate and is associated with fewer GI side-effects.

In view of WHO policy and risks of supplementation, there is a need to determine the potential for harm, and if novel forms of iron supplements are safer.
Detailed Description

The World Health Organization (WHO) set a Global Nutrition Target to reduce anemia in women of reproductive age by 50% by 2025. In 2016, the WHO implemented a global policy recommending oral iron supplementation (60 mg daily for 12 weeks) for all women where anemia prevalence is more than 40%, such as in Cambodia.

However, recent studies have shown the prevalence of iron deficiency to be low in Cambodian women. If iron deficiency is not the cause of anemia, then iron supplementation will not be effective at treating it. Further, iron supplementation may be harmful in some individuals, especially those with anemia caused by genetic blood disorders (which are common in Cambodia), as these individuals are already at an increased risk of iron overload. The risks are made greater by the fact that the type of iron that is commonly used in supplements (ferrous sulfate) is poorly absorbed. Typically, less than 20% is absorbed in the gut; the remaining 80% is unabsorbed in the colon where it can increase the risk of pathogen growth and gut inflammation.

To investigate the safety of untargeted iron supplementation, we will undertake a new study in Cambodia, where we will evaluate a newer type of iron supplement that may be absorbed better, and thus, safer than the conventional type. We will recruit non-pregnant women (18-45 years) and ask them to take one of the two forms of iron (ferrous sulfate or ferrous bisglycinate) or a placebo for 12 weeks (in line with the WHO global policy). We will measure hemoglobin and ferritin levels, which are markers of anemia and iron status, and markers of gut inflammation and gut pathogen abundance, before and after the intervention. This study will contribute to the evidence for safe and effective iron supplementation for women worldwide.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
12-week double-blind, three-arm, placebo-controlled randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
The manufacturers of the tablets (Dr. Simon Wood, Natural Factors) will be responsible for allocation concealment of the three tablet formulations at time of packaging. All tablets will be non-distinguishable in size, colour, and packaging. Trial investigators, research staff, and participants will all be blinded to the assigned interventions
Primary Purpose: Treatment
Condition  ICMJE
  • Anemia, Iron Deficiency
  • Anemia
  • Intestinal Inflammation
  • Inflammation
  • Intestine; Complaints
Intervention  ICMJE
  • Dietary Supplement: Ferrous sulfate
    60 mg elemental iron as ferrous sulfate
    Other Names:
    • iron sulfate
    • ferrous sulphate
    • iron sulphate
    • Iron(II) sulfate
  • Dietary Supplement: Ferrous Bisglycinate
    18 mg elemental iron as ferrous bisglycinate
    Other Names:
    • iron amino acid chelate
    • Iron glycinate
    • Bisglycine iron(II) salt
    • Iron(II) bisglycinate
    • Ferrous Bis-glycinate
  • Dietary Supplement: Placebo of microcrystalline cellulose
    placebo
    Other Name: Control
Study Arms  ICMJE
  • Active Comparator: Ferrous Sulfate
    Iron will be given orally in the form of tablets. A supplement of 60 mg will be taken daily for 12 weeks. World Health Organization standard dose and commonly used form of iron.
    Intervention: Dietary Supplement: Ferrous sulfate
  • Experimental: Ferrous Bisglycinate
    Iron will be given orally in the form of tablets. A supplement of 18 mg will be taken daily for 12 weeks. Ferrous bisglycinate has a bioavailability 2-4x greater than ferrous sulfate.
    Intervention: Dietary Supplement: Ferrous Bisglycinate
  • Placebo Comparator: Placebo
    Placebo will be given orally in the form of tablets as a control made of microcrystalline cellulose.
    Intervention: Dietary Supplement: Placebo of microcrystalline cellulose
Publications * Fischer JA, Pei LX, Goldfarb DM, Albert A, Elango R, Kroeun H, Karakochuk CD. Is untargeted iron supplementation harmful when iron deficiency is not the major cause of anaemia? Study protocol for a double-blind, randomised controlled trial among non-pregnant Cambodian women. BMJ Open. 2020 Aug 16;10(8):e037232. doi: 10.1136/bmjopen-2020-037232.

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 10, 2019) 		480
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Actual Primary Completion Date May 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • apparently healthy
  • consent to participate in the study and provide blood, flocked rectal swab and stool samples
  • expected to reside in the study location for the study period.

Exclusion Criteria:

  • any known illness or disease
  • pregnant
  • taking antibiotics, non-steroidal anti-inflammatory drugs, dietary supplements, or vitamin and mineral supplements in the previous 12 weeks.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 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 Cambodia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04017598
Other Study ID Numbers  ICMJE H18-02610
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is not a plan to make IPD available.
Responsible Party Crystal Karakochuk, University of British Columbia
Study Sponsor  ICMJE University of British Columbia
Collaborators  ICMJE
  • Helen Keller International
  • NCHADS - Ministry of Health of Cambodia
  • BC Children's Hospital Research Institute
  • The National Institute of Public Health Laboratory, Phnom Penh
Investigators  ICMJE Not Provided
PRS Account University of British Columbia
Verification Date April 2021

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

治疗医院

新药特效药

前沿医讯