Effect of CFR and Iron Supplementation on Iron Status and Gut Microbiota of 1-2 Years Old Myanmar Children

Iron Deficiency Anemia Clinical Trial

— CFR  

Official title:

The Effect of Optimized Local Food-based Complementary Feeding With or Without Iron Supplementation on Iron Status and Gut Microbiota of 1-2 Years Old Myanmar Children

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01758159
• Other study ID #: HHlaing CFR Myanmar
• Status: Active, not recruiting
• Phase: Phase 3
• First received: December 18, 2012
• Last updated: September 29, 2013
• Start date: February 2013
• Est. completion date: April 2014

Study information

• Verified date: September 2013
• Source: SEAMEO Regional Centre for Food and Nutrition
• Contact: n/a
• Is FDA regulated: No
• Health authority: The Ethical Review Committee, Department of Health, Ministry of Health: Myanmar
• Study type: Interventional

Clinical Trial Summary

Complementary feeding diet in developing countries cannot meet iron requirements of infants and young children. Iron supplementation is mostly used to treat iron deficiency whereas iron fortification is cost-effective strategy to control iron deficiency in developing countries. However, a recent study showed that iron fortification imposed negative impact on gut microbiota by increasing colonization of gut pathogen over beneficial bacteria. Gut microbiota plays essential roles in nutrient absorption, vitamin synthesis; intestinal mucosal barrier function and pathogen displacement. Iron is essential for growth and virulence of most gut pathogens and so iron supplementation might have similar negative impact on gut microbiota composition. Therefore, nutrition interventions would not be justified by assessing micronutrient status alone ignoring any possible deterioration of gut microbiota. The investigators hypothesized that optimizing the nutrient intake from locally available foods according to complementary feeding recommendation (CFR) can improve the iron status of these children while maintaining healthy gut microbiota composition.

A randomized, placebo-controlled, community-based, intervention trial will be conducted in Ayeyarwady division of Myanmar where childhood undernutrition is prevalent. The aim of this study is to compare the effect of optimized CFR to iron supplementation on iron status and gut microbiota composition of 1-2years old Myanmar children. Cluster randomization will be done at the village level to randomly allocate the villages into CFR or non-CFR villages. Individual randomization will be done to randomly assign each child into iron or placebo syrup so that individual children will receive one of 4 treatment groups (CFR, Fe, CFR + Fe, and Control) for a period of 24 weeks. Based on expected between-groups difference of hemoglobin 5g/L, at 80% power, 5% level of significance, 15% drop-out rate; after taking into account the cluster effect; required sample will be 109 per group (total = 436). A sub-sample of 15 children from each group will be randomly selected for gut microbiota assessment (total = 60). Blood samples for iron status and stool samples for gut microbiota assessment will be collected at baseline and endline. Anthropometric measurements, usual intake of iron and infectious disease morbidity will also be assessed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 433
• Est. completion date: April 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 12 Months to 18 Months

Eligibility

Inclusion Criteria:

• Age between 12-18 months

• Apparently healthy

• Not consuming regular iron containing supplements during the last 4 months

Exclusion Criteria:

• With severe anemia (Hemoglobin < 50g/L)

• Malaria test positive with Immuno-chromatographic test (ICT)

• Mothers/ Caregivers are not willing to join the study

• Suffer from chronic diseases which can affect their dietary intake

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Iron Deficiency
• Iron Deficiency Anemia

Intervention

Dietary Supplement:
• Iron supplementation

Other:
• CFR
Complementary feeding with locally available foods according to optimized complementary feeding recommendation (CFR)

Locations

Country	Name	City	State
Myanmar	National Nutrition Center, Ministry of Health, Myanmar	Pan Ta Naw Township and Kyaungon Township	Ayeyarwady Division

Sponsors (3)

Lead Sponsor	Collaborator
SEAMEO Regional Centre for Food and Nutrition	National Health Laboratory (Department of Health,Ministry of Health, Myanmar), National Nutrition Center, Department of Health, Ministry of Health, Myanmar

Country where clinical trial is conducted

Myanmar, 

References & Publications (12)

Fahmida U, Preedy VR. Food-Based Complementary Feeding and Its Impact on Growth: Southeast Asian Perspectives, Handbook of Growth and Growth Monitoring in Health and Disease. Springer New York; 2012. p. 1599-610.

Ferguson EL, Darmon N, Fahmida U, Fitriyanti S, Harper TB, Premachandra IM. Design of optimal food-based complementary feeding recommendations and identification of key "problem nutrients" using goal programming. J Nutr. 2006 Sep;136(9):2399-404. — View Citation

Gibson RS, Anderson VP. A review of interventions based on dietary diversification or modification strategies with the potential to enhance intakes of total and absorbable zinc. Food Nutr Bull. 2009 Mar;30(1 Suppl):S108-43. Review. — View Citation

Gibson RS, Ferguson EL, Lehrfeld J. Complementary foods for infant feeding in developing countries: their nutrient adequacy and improvement. Eur J Clin Nutr. 1998 Oct;52(10):764-70. — View Citation

Iannotti LL, Tielsch JM, Black MM, Black RE. Iron supplementation in early childhood: health benefits and risks. Am J Clin Nutr. 2006 Dec;84(6):1261-76. Review. — View Citation

Monira S, Nakamura S, Gotoh K, Izutsu K, Watanabe H, Alam NH, Endtz HP, Cravioto A, Ali SI, Nakaya T, Horii T, Iida T, Alam M. Gut microbiota of healthy and malnourished children in bangladesh. Front Microbiol. 2011 Nov 21;2:228. doi: 10.3389/fmicb.2011.00228. eCollection 2011. — View Citation

Prakash S, Rodes L, Coussa-Charley M, Tomaro-Duchesneau C. Gut microbiota: next frontier in understanding human health and development of biotherapeutics. Biologics. 2011;5:71-86. doi: 10.2147/BTT.S19099. Epub 2011 Jul 11. — View Citation

Santika O, Fahmida U, Ferguson EL. Development of food-based complementary feeding recommendations for 9- to 11-month-old peri-urban Indonesian infants using linear programming. J Nutr. 2009 Jan;139(1):135-41. doi: 10.3945/jn.108.092270. Epub 2008 Dec 3. — View Citation

World Health Organization. Conclusions and recommendations of the WHO Consultation on prevention and control of iron deficiency in infants and young children in malaria-endemic areas. Food Nutr Bull. 2007 Dec;28(4 Suppl):S621-7. Review. — View Citation

Yap GC, Chee KK, Hong PY, Lay C, Satria CD, Sumadiono, Soenarto Y, Haksari EL, Aw M, Shek LP, Chua KY, Zhao Y, Leow D, Lee BW. Evaluation of stool microbiota signatures in two cohorts of Asian (Singapore and Indonesia) newborns at risk of atopy. BMC Microbiol. 2011 Aug 26;11:193. doi: 10.1186/1471-2180-11-193. — View Citation

Zimmermann MB, Chassard C, Rohner F, N'goran EK, Nindjin C, Dostal A, Utzinger J, Ghattas H, Lacroix C, Hurrell RF. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr. 2010 Dec;92(6):1406-15. doi: 10.3945/ajcn.110.004564. Epub 2010 Oct 20. — View Citation

Zimmermann MB, Hurrell RF. Nutritional iron deficiency. Lancet. 2007 Aug 11;370(9586):511-20. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Iron status	Iron status indicators including hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR) concentration will be measured at the beginning and at the end of 24 weeks intervention.	Baseline (at week 0) and Endline (at week 24)	No
Primary	Change in Gut microbiota composition	Sub-samples analysis from 60 children (15 children from each group) will be done to detect the DNA-copy number of Total bacteria, Lactobacillus, Bifidobacteria and Enterobacteria in group and Enteropathogenic E.coli (EPEC), Enterotoxigenic E.coli (ETEC) and Enteroaggregative E.coli (EAEC) species by PCR analysis at the beginning and at the end of 24 weeks intervention.	Baseline (at week 0), Endline (at week 24)	No