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

Inflammation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04017598
• Other study ID #: H18-02610
• Status: Completed
• Phase: Phase 4
• Start date: December 10, 2019
• Est. completion date: December 1, 2023

Study information

• Verified date: May 2024
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 480
• Est. completion date: December 1, 2023
• Est. primary completion date: May 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron Deficiency
• Anemia, Iron-Deficiency
• Inflammation
• Intestinal Inflammation
• Intestine; Complaints

Intervention

Dietary Supplement:
• Ferrous sulfate
60 mg elemental iron as ferrous sulfate
• Ferrous Bisglycinate
18 mg elemental iron as ferrous bisglycinate
• Placebo of microcrystalline cellulose
placebo

Locations

Country	Name	City	State
Cambodia	Prey Kuy, Srayov and Tboung Krapeu Health Centres	Kampong Thom

Sponsors (5)

Lead Sponsor	Collaborator
University of British Columbia	BC Children's Hospital Research Institute, Helen Keller International, NCHADS - Ministry of Health of Cambodia, The National Institute of Public Health Laboratory, Phnom Penh

Country where clinical trial is conducted

Cambodia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Reported side effects	(e.g., gastrointestinal pain) as a quality of life measure.	Continuous over 12 weeks
Other	Genetic hemoglobinopathies	Genotyping to detect the presence of the most common hemoglobinopathies	Baseline
Other	Gut Pathogen abundance	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).	12 weeks
Primary	Serum Ferritin	Serum ferritin concentration (µg/l) at 12 weeks	12 weeks
Primary	Fecal calprotectin	Fecal calprotectin concentration (mg/kg stool) at 12 weeks as a measure of gut inflammation.	12 weeks
Secondary	Gut pathogen abundance	Real-time PCR nucleic acid amplification assay with an enteric bacterial panel.	12 weeks
Secondary	Gut parasite abundance	Real-time PCR nucleic acid amplification assay with an enteric parasite panel.	12 weeks
Secondary	DNA damage	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).	12 weeks
Secondary	Alpha-1 acid glycoprotein (AGP, g/l)		12 weeks
Secondary	C-reactive protein (CRP, mg/l)		12 weeks
Secondary	Hemoglobin (g/L)		12 weeks
Secondary	Folate (ng/ml)		12 weeks
Secondary	Vitamin B12 (pmol/l)		12 weeks