Is Iron Supplementation Harmful in Populations Where Iron Deficiency is Not the Cause of Anemia? A 12 Week Randomized Controlled Trial in Cambodia

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

Sponsors

Lead sponsor: University of British Columbia

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

Source University of British Columbia
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.

Overall Status Active, not recruiting
Start Date December 10, 2019
Completion Date May 2020
Primary Completion Date May 2020
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Serum Ferritin 12 weeks
Fecal calprotectin 12 weeks
Secondary Outcome
Measure Time Frame
Gut pathogen abundance 12 weeks
Gut parasite abundance 12 weeks
DNA damage 12 weeks
Alpha-1 acid glycoprotein (AGP, g/l) 12 weeks
C-reactive protein (CRP, mg/l) 12 weeks
Hemoglobin (g/L) 12 weeks
Folate (ng/ml) 12 weeks
Vitamin B12 (pmol/l) 12 weeks
Enrollment 480
Condition
Intervention

Intervention type: Dietary Supplement

Intervention name: Ferrous sulfate

Description: 60 mg elemental iron as ferrous sulfate

Arm group label: Ferrous Sulfate

Intervention type: Dietary Supplement

Intervention name: Ferrous Bisglycinate

Description: 18 mg elemental iron as ferrous bisglycinate

Arm group label: Ferrous Bisglycinate

Intervention type: Dietary Supplement

Intervention name: Placebo of microcrystalline cellulose

Description: placebo

Arm group label: Placebo

Other name: Control

Eligibility

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.

Gender: Female

Gender based: Yes

Minimum age: 18 Years

Maximum age: 45 Years

Healthy volunteers: Accepts Healthy Volunteers

Location
facility Prey Kuy, Srayov and Tboung Krapeu Health Centres
Location Countries

Cambodia

Verification Date

April 2020

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: University of British Columbia

Investigator full name: Crystal Karakochuk

Investigator title: Principle Investigator

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: Ferrous Sulfate

Arm group type: Active Comparator

Description: 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.

Arm group label: Ferrous Bisglycinate

Arm group type: Experimental

Description: 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.

Arm group label: Placebo

Arm group type: Placebo Comparator

Description: Placebo will be given orally in the form of tablets as a control made of microcrystalline cellulose.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: 12-week double-blind, three-arm, placebo-controlled randomized controlled trial

Primary purpose: Treatment

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

Source: ClinicalTrials.gov