Is Iron Deficiency the Cause of Anemia Among Women in Cambodia?

NCT02481375 | Completed Results

• 1 other identifier: H15-00933
• Study Type: interventional
• Target: 809
• Locations: 1 country
• Sites: 1

Brief Summary

Globally, the most common cause of anemia is thought to be iron deficiency anemia (IDA). This was assumed to be the major cause of anemia in Cambodia, because Cambodian diets, which consist mainly of rice, lack iron-rich animal food sources. However, our findings from a previous study in Cambodia (a Canadian government funded study investigating multiple interventions to improve food and nutrition security) showed that IDA is almost non-existent and challenges this assumption. In a cross-sectional survey of 450 women from rural Cambodia, only 1.0% had Hb and ferritin levels indicative of IDA (Hb \<120 g/L and ferritin \<15 μg/L). A national survey conducted by UNICEF in 2014 found similarly low rates of IDA (Dr. Arnaud Laillou, UNICEF Cambodia). Further, other micronutrients known to be associated with anemia were also low (\<3%) including folate and vitamins B12 and B6. In addition, 54% of the Prey Veng women had a genetic Hb disorder (e.g., α-thalassemias), which are inherited diseases that can result in a defective Hb structure and/or impair Hb production, either of which can reduce Hb concentration and increase the risk of anemia. Further, genetic Hb disorders cause ferritin and soluble transferrin receptor (sTfR) concentrations to increase, which reduce the diagnostic sensitivity of these biomarkers to identify IDA. In 2011, the Cambodian Ministry of Health (MOH) recommended weekly iron and folic acid (IFA) supplementation for all women of reproductive age, consistent with WHO guidelines. However, if iron deficiency is not a major cause of anemia, then at best supplementation is a waste of valuable resources and at worst could cause harm. Further, the justification for provision of multiple micronutrients among this population has not yet been proven, despite the push from some organizations such as the WHO. There is an urgent need to conduct a trial to clarify whether iron or other micronutrient deficiencies are a major cause of anemia in Cambodia. Research Objectives:

1. 1.To compare Hb concentration (g/L) after 12-weeks of supplementation in women to determine if iron significantly improves Hb concentration, compared to a placebo;
2. 2.To compare Hb concentration (g/L) across the four groups (multiple micronutrients with iron, multiple micronutrients without iron, iron alone, and placebo) after 12-weeks; and
3. 3.To determine which of the hematological indicators (ferritin, sTfR, reticulocyte count and hepcidin) have the strongest diagnostic ability to predict responsiveness to iron therapy after 12-weeks using receiver operating characteristic (ROC) analyses.

Conditions

Anemia; Iron Deficiency; Hemoglobin Disorder; Infection; Inflammation

Keywords

iron; ferritin; soluble transferrin receptor; hepcidin; reticulocyte count; hemoglobin; supplementation

Outcome Measures

Primary Outcomes (1)

• Hemoglobin Levels at 12-weeks. Marginal Means (95% CI).

  Marginal means (95% CI) at 12-weeks using a generalized mixed-effects model with adjustments for baseline values and village clusters. Multiple imputation was used to impute n=49 missing values for hemoglobin at endline.

  12-weeks of intervention

Study Arms (4)

Multiple micronutrients with iron

EXPERIMENTAL

Multiple micronutrient formulations were based on the UNICEF/WHO/UNU standard formulation for pregnant and lactating women (UNIMMAP) with increased iron (from 30 mg to 60 mg elemental iron) for comparability to the iron only group (60 mg). This formulation has 15 micronutrients including iron. Women will receive the multiple micronutrient with iron for 12 weeks.

Dietary Supplement: Multiple micronutrients; Dietary Supplement: Iron

Multiple micronutrients without iron

ACTIVE COMPARATOR

This formulation has the 14 micronutrients included in the UNIMMAP formulation, but does not include iron. Women will receive the multiple micronutrient without iron for 12 weeks.

Dietary Supplement: Multiple micronutrients

Iron only

ACTIVE COMPARATOR

This formulation only has 60 mg elemental iron. Women will receive iron for 12 weeks.

Dietary Supplement: Iron

Placebo

PLACEBO COMPARATOR

This formulation is a placebo. Women will receive a placebo for 12 weeks.

Dietary Supplement: Placebo

Interventions

Multiple micronutrients DIETARY_SUPPLEMENT

12-wk supplementation of vitamin A, B1, B2, B6 ,B12, D, E, niacin, folic acid, zinc, copper, selenium, iodine

Multiple micronutrients with iron; Multiple micronutrients without iron

Iron DIETARY_SUPPLEMENT

12-wk supplementation of iron

Also known as: 60 mg elemental iron

Iron only; Multiple micronutrients with iron

Placebo DIETARY_SUPPLEMENT

12-wk supplementation of placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• women between 18-45 years
• healthy except for Hb = or \<117 g/L
• consent to participate in the study.

You may not qualify if:

• women with Hb \>117 g/L
• women who are currently pregnant
• women who are taking medications, including any dietary supplements.

Sponsors & Collaborators

• University of British Columbia: lead
• Micronutrient Initiative: collaborator
• DSM Nutritional Products, Inc.: collaborator
• International Development Research Centre, Canada: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Helen Keller International: collaborator

Study Sites (1)

Kampong Chhnang province

Kampong Chhnang, Kampong Chhnang, Cambodia

Location

Related Publications (4)

• Williams BA, Cochrane KM, Fischer JAJ, Aljaadi AM, McAnena L, Ward M, McNulty H, Kroeun H, Green TJ, Whitfield KC, Karakochuk CD. The Homozygous Hemoglobin EE Variant Is Associated with Poorer Riboflavin Status in Cambodian Women of Reproductive Age. J Nutr. 2020 Jul 1;150(7):1943-1950. doi: 10.1093/jn/nxaa119.

  PMID: 32433728 DERIVED

• Holmes JB, Kroeun H, Houghton LA, Gibson RS, Harding KB, De-Regil LM, Kraemer K, Barr SI, Karakochuk CD. Including 60 mg Elemental Iron in a Multiple Micronutrient Supplement Blunts the Increase in Serum Zinc after 12 Weeks of Daily Supplementation in Predominantly Anemic, Nonpregnant Cambodian Women of Reproductive Age. J Nutr. 2019 Sep 1;149(9):1503-1510. doi: 10.1093/jn/nxz097.

  PMID: 31174215 DERIVED

• Karakochuk CD, Barker MK, Whitfield KC, Barr SI, Vercauteren SM, Devlin AM, Hutcheon JA, Houghton LA, Prak S, Hou K, Chai TL, Stormer A, Ly S, Devenish R, Oberkanins C, Puhringer H, Harding KB, De-Regil LM, Kraemer K, Green TJ. The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: a 2 x 2 factorial, double-blind, randomized controlled supplementation trial. Am J Clin Nutr. 2017 Jul;106(1):233-244. doi: 10.3945/ajcn.116.140996. Epub 2017 May 10.

  PMID: 28490515 DERIVED

• Rappaport AI, Barr SI, Green TJ, Karakochuk CD. Variation in haemoglobin measurement across different HemoCue devices and device operators in rural Cambodia. J Clin Pathol. 2017 Jul;70(7):615-618. doi: 10.1136/jclinpath-2017-204351. Epub 2017 Mar 8.

  PMID: 28275044 DERIVED

MeSH Terms

Conditions

Anemia; Iron Deficiencies; Hemoglobinopathies; Infections; Inflammation

Interventions

Iron

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Results Point of Contact

• Title: Crystal Karakochuk
• Organization: University of British Columbia

crystal.karakochuk@ubc.ca

604 822 0421

Study Officials

• Kroeun Hou, MPH

  Helen Keller International, Cambodia

  STUDY CHAIR

• Sophonneary Prak, MPH

  National Maternal and Child Health Center, Ministry of Health, Cambodia

  STUDY CHAIR

• Crystal Karakochuk, MSc, PhD(c)

  University of British Columbia

  STUDY CHAIR

• Tim Green, PhD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 25, 2015
• Study Start: July 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: May 14, 2019
• Results First Posted: October 24, 2018

Record last verified: 2019-04

Locations

CA (1)