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

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ClinicalTrials.gov Identifier: NCT02481375
Recruitment Status : Completed
First Posted : June 25, 2015
Last Update Posted : June 7, 2016
Sponsor:
Collaborators:
Micronutrient Initiative
DSM Nutritional Products, Inc.
International Development Research Centre, Canada
Canadian Institutes of Health Research (CIHR)
Helen Keller International
Information provided by (Responsible Party):
University of British Columbia

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. 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. 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. 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.

Methods: A 2 x 2 factorial randomized controlled trial will be conducted over 12 weeks. A total of ~800 women (18-45 y) with mild or moderate anemia will be recruited and randomized to 1 of 4 groups: multiple micronutrients with iron, multiple micronutrients without iron, iron alone or placebo. Blood will be collected at baseline and at 1 and 12 weeks after the intervention and assessed for Hb, hematological biomarkers, inflammation and genetic Hb disorders. The investigators will use a general linear model to measure differences in Hb concentration across the four groups after the intervention. Receiver operating characteristic curves will be used to determine the diagnostic ability of the multiple hematological indicators to predict responsiveness to iron therapy.


Condition or disease Intervention/treatment Phase
Anemia Iron Deficiency Hemoglobin Disorder Infection Inflammation Dietary Supplement: Multiple micronutrients Dietary Supplement: Iron Dietary Supplement: Placebo Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 809 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Is Iron Deficiency the Cause of Anemia Among Women of Reproductive Age in Cambodia? A 2 x 2 Factorial Double Blind Randomized Controlled Trial of Oral Iron and Multiple Micronutrient Supplementation
Study Start Date : July 2015
Actual Primary Completion Date : January 2016
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Iron

Arm Intervention/treatment
Experimental: Multiple micronutrients with iron

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

Dietary Supplement: Iron
12-wk supplementation of iron
Other Name: 60 mg elemental iron

Active Comparator: Multiple micronutrients without iron

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

Active Comparator: Iron only

This formulation only has 60 mg elemental iron.

Women will receive iron for 12 weeks.

Dietary Supplement: Iron
12-wk supplementation of iron
Other Name: 60 mg elemental iron

Placebo Comparator: Placebo

This formulation is a placebo.

Women will receive a placebo for 12 weeks.

Dietary Supplement: Placebo
12-wk supplementation of placebo




Primary Outcome Measures :
  1. Hemoglobin response [ Time Frame: 12-weeks of intervention ]

Secondary Outcome Measures :
  1. Ferritin response [ Time Frame: 12-weeks of intervention ]
  2. Composite outcome measure: comparison of multiple biomarkers (ferritin, sTfR, reticulocyte count, hepcidin) using the area under the curve analyses (sensitivity and specificity) to indicate responsiveness to iron therapy [ Time Frame: 12-weeks of intervention ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02481375


Locations
Cambodia
Kampong Chhnang province
Kampong Chhnang province, Cambodia
Sponsors and Collaborators
University of British Columbia
Micronutrient Initiative
DSM Nutritional Products, Inc.
International Development Research Centre, Canada
Canadian Institutes of Health Research (CIHR)
Helen Keller International
Investigators
Study Chair: 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
Principal Investigator: Tim Green, PhD University of British Columbia

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT02481375     History of Changes
Other Study ID Numbers: H15-00933
First Posted: June 25, 2015    Key Record Dates
Last Update Posted: June 7, 2016
Last Verified: June 2016

Keywords provided by University of British Columbia:
iron
ferritin
soluble transferrin receptor
hepcidin
reticulocyte count
hemoglobin
supplementation

Additional relevant MeSH terms:
Inflammation
Anemia
Anemia, Iron-Deficiency
Hemoglobinopathies
Pathologic Processes
Hematologic Diseases
Anemia, Hypochromic
Iron Metabolism Disorders
Metabolic Diseases
Genetic Diseases, Inborn
Iron
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs