Sustainable Intervention of Supplementation to Improve Kid's Growth Study

NCT04564222 | Active Not Recruiting DMC

• 1 other identifier: 216447/Z/19/Z
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 1

Brief Summary

Our earlier research has highlighted a high prevalence of anaemia, micronutrient deficiencies, and impaired infant growth among lactating women and infants in Sumedang district, West Java, Indonesia that were associated with large deficits in their micronutrient intakes. In response to these disturbing findings we have developed the micronutrient- enriched crackers (MEC) based on powdered eggshells and chicken liver, a readily available and affordable, local animal-source food. We will supply these MEC or a placebo, manufactured locally, weekly to a group of women in Sumedang district from 8-14 weeks gestation to 5 months post-partum in an effort to enrich the micronutrient content of the daily diets of the treatment group so they no longer have any dietary shortfalls in micronutrients. Our overall aim is to determine if MEC consumed daily by mothers for 6 months during pregnancy improves the birth length of their infants, and if daily consumption of MEC is continued daily to 5 months post-partum enhances infant linear growth compared to the placebo. This study is funded by the UK Wellcome Trust, the grant reference number is 216447/Z/19/Z.

Conditions

Birth Length; Linear Growth; Micronutrients; Dietary Intakes

Keywords

Chicken Liver; Eggshell; Crackers; Pregnancy; Lactating Mother; Indonesia

Outcome Measures

Primary Outcomes (2)

• Birth length

  All measurements will be taken to the nearest millimetre (mm) using standardized techniques and trained anthropometrists using a portable infantometer (SECA 417, measuring range: 10-100 cm). The measurements will be made on nude infants and will be recorded in duplicate, or triplicate if the difference between the first and second measurement is more than the recommended range (i.e., 7 mm).

  24 hours after birth

• Attained linear growth and growth velocity

  All length measurement will be taken to the nearest millimetre (mm) using standardized techniques by trained anthropometrists using a portable infantometer (SECA 417, measuring range: 10-100 cm) The measurements will be made on nude infants and will be recorded in duplicate, or triplicate if the difference between the first and second measurement is more than the recommended range (i.e., 7 mm).

  5 months (+/- 1 week) post partum

Secondary Outcomes (9)

• Birth weight

  24 hours after birth

• Maternal haemoglobin level

  35-36 gestational age and 5 months (+/- 1 week) post partum

• Maternal food intake

  35-36 weeks gestational age, 2 months (+/- 1 week) and 5 months (+/- 1 week) post partum

• Status of breastfed infants (exclusive vs. non-exclusive) and breast milk volume

  5 months (+/- 1 week) post partum

• Breast milk micronutrient concentration

  5 months (+/- 1 week) post partum

Study Arms (2)

Micronutrient Enriched Crackers (MECs)

EXPERIMENTAL

Micronutrient Enriched Crackers (MECs) are a deep-fried snack product rich in iron, zinc, calcium, and vitamin A made from chicken liver and chicken eggshell powder. Consume daily, 75 gram/day, during pregnancy (from 8-14 weeks gestation to delivery) and lactation (from delivery to 5 months post-partum).

Dietary Supplement: Micronutrient Enriched Crackers (MECs)

Placebo

PLACEBO COMPARATOR

Placebo Crackers are a deep-fried snack product made from the basic cracker ingredients (mainly wheat flour) with the addition of Pangium edule seeds to provide a color similar to the intervention product (MECs). Consume daily, 75 gram/day, during pregnancy (from 8-14 weeks gestation to delivery) and lactation (from delivery to 5 months post-partum).

Dietary Supplement: Placebo

Interventions

Micronutrient Enriched Crackers (MECs) DIETARY_SUPPLEMENT

MECs are manufactured according to the Standard Operational Procedures which have been developed taking into account the Hazard Analysis and Critical Control Point (HACCP) to maintain quality and safety and ensure the "Ready-to-eat MEC products" are safe. Data on the micronutrient concentrations and any potential bacteriological (Salmonella sp is negative, Bacillus cereus, Enterobacteriaceae, and Coagulase positive streptococci level are considered safe) and chemical contaminants (Pb, Hg, Cd, As, and Sn are not detectable) in the MEC products have been obtained from analysis in the laboratory of Saraswanti Indo Genetech, which has been accredited by KAN LP-184-IDN with SNI ISO/IEC 17025: 2008. Laboratory analysis of MEC products will be repeated at the middle and the end of the RCT to check on the quality and safety of the MEC product.

Also known as: SISTIK

Micronutrient Enriched Crackers (MECs)

Placebo DIETARY_SUPPLEMENT

Placebo crackers are manufactured according to SOPs which have been developed taking into account the HACCP to maintain quality and safety and ensure the "Ready-to-eat placebo products" are safe. Data on the micronutrient concentrations and any potential bacteriological (Salmonella sp is negative, Bacillus cereus, Enterobacteriaceae, and Coagulase positive streptococci level are considered safe) and chemical contaminants (Pb, Hg, Cd, As, and Sn are not detected) in the placebo have been obtained based on the analysis in the laboratory of Saraswanti Indo Genetech, which has been accredited by KAN LP-184-IDN with SNI ISO/IEC 17025: 2008. Laboratory analysis of placebo samples will be repeated at the middle and the end of the RCT to check on the quality and safety of the placebo product.

Placebo

Eligibility Criteria

• Age: 19 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant women
• Gestational age 7-13 weeks at the time of the screening process and be willing to take part in an intervention study at 8-14 weeks gestation
• Permanent residents who do not plan to move in the next 1 year

You may not qualify if:

• Mothers who have chronic diseases such as hypertension (blood pressure \> 140/90 mmHg) or under treatment for hypertension, diabetes (non-fasting blood sugar \> 200 mg/dL)/ under treatment for diabetes, hypercholesterolemia (blood total cholesterol \> 240 mg/dL), hyperuricemia (blood uric acid \> 6 mg/dL), have had a history of tuberculosis or under treatment for tuberculosis; or under treatment for other chronic diseases that required a long treatment, such as cancer, heart disease, epilepsy, etc.
• Have a history of preeclampsia/eclampsia and gestational diabetes in their previous pregnancy
• Have a risk of chronic energy deficiency (mid-upper arm circumference \< 23.5 cm)
• Have severe anaemia (haemoglobin \< 70 g/L or \< 7 g/dL)
• Have a history of allergy to chicken liver and/or eggs

Sponsors & Collaborators

• SEAMEO Regional Centre for Food and Nutrition: lead
• Universitas Padjadjaran: collaborator
• University of Otago: collaborator
• USDA, Western Human Nutrition Research Center: collaborator
• VitMin Lab: collaborator
• International Food Policy Research Institute: collaborator

Study Sites (1)

Tanjungsari, Pamulihan, and Sukasari Subdistrict

Sumedang, West Java, Indonesia

Location

Related Publications (22)

• Daniels L, Gibson RS, Diana A, Haszard JJ, Rahmannia S, Luftimas DE, Hampel D, Shahab-Ferdows S, Reid M, Melo L, Lamers Y, Allen LH, Houghton LA. Micronutrient intakes of lactating mothers and their association with breast milk concentrations and micronutrient adequacy of exclusively breastfed Indonesian infants. Am J Clin Nutr. 2019 Aug 1;110(2):391-400. doi: 10.1093/ajcn/nqz047.

  PMID: 31152543 BACKGROUND

• Diana A, Haszard JJ, Purnamasari DM, Nurulazmi I, Luftimas DE, Rahmania S, Nugraha GI, Erhardt J, Gibson RS, Houghton L. Iron, zinc, vitamin A and selenium status in a cohort of Indonesian infants after adjusting for inflammation using several different approaches. Br J Nutr. 2017 Nov;118(10):830-839. doi: 10.1017/S0007114517002860.

  PMID: 29189196 BACKGROUND

• Diana A, Mallard SR, Haszard JJ, Purnamasari DM, Nurulazmi I, Herliani PD, Nugraha GI, Gibson RS, Houghton L. Consumption of fortified infant foods reduces dietary diversity but has a positive effect on subsequent growth in infants from Sumedang district, Indonesia. PLoS One. 2017 Apr 20;12(4):e0175952. doi: 10.1371/journal.pone.0175952. eCollection 2017.

  PMID: 28426828 BACKGROUND

• Domellof M, Dewey KG, Lonnerdal B, Cohen RJ, Hernell O. The diagnostic criteria for iron deficiency in infants should be reevaluated. J Nutr. 2002 Dec;132(12):3680-6. doi: 10.1093/jn/132.12.3680.

  PMID: 12468607 BACKGROUND

• Dror DK, Allen LH. Overview of Nutrients in Human Milk. Adv Nutr. 2018 May 1;9(suppl_1):278S-294S. doi: 10.1093/advances/nmy022.

  PMID: 29846526 BACKGROUND

• Dror DK, Allen LH. Retinol-to-Fat Ratio and Retinol Concentration in Human Milk Show Similar Time Trends and Associations with Maternal Factors at the Population Level: A Systematic Review and Meta-Analysis. Adv Nutr. 2018 May 1;9(suppl_1):332S-346S. doi: 10.1093/advances/nmy021.

  PMID: 29846525 BACKGROUND

• Duizer LM, Diana A, Rathomi HS, Luftimas DE, Rahmannia S, Santi W, Nugraha GI, Haszard JJ, Gibson RS, Houghton LA. An Acceptability Trial of Desiccated Beef Liver and Meat Powder as Potential Fortifiers of Complementary Diets of Young Children in Indonesia. J Food Sci. 2017 Sep;82(9):2206-2212. doi: 10.1111/1750-3841.13807. Epub 2017 Jul 26.

  PMID: 28746725 BACKGROUND

• Engle-Stone R, Haskell MJ, Ndjebayi AO, Nankap M, Erhardt JG, Gimou MM, Brown KH. Plasma retinol-binding protein predicts plasma retinol concentration in both infected and uninfected Cameroonian women and children. J Nutr. 2011 Dec;141(12):2233-41. doi: 10.3945/jn.111.145805. Epub 2011 Nov 2.

  PMID: 22049292 BACKGROUND

• Gibson RS, Hotz C. Dietary diversification/modification strategies to enhance micronutrient content and bioavailability of diets in developing countries. Br J Nutr. 2001 May;85 Suppl 2:S159-66. doi: 10.1079/bjn2001309.

  PMID: 11509105 BACKGROUND

• Human energy requirements: report of a joint FAO/ WHO/UNU Expert Consultation. Food Nutr Bull. 2005 Mar;26(1):166. No abstract available.

  PMID: 15810802 BACKGROUND

• Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001. Available from http://www.ncbi.nlm.nih.gov/books/NBK222310/

  PMID: 25057538 BACKGROUND

• Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK56070/

  PMID: 21796828 BACKGROUND

• International Zinc Nutrition Consultative Group (IZiNCG); Brown KH, Rivera JA, Bhutta Z, Gibson RS, King JC, Lonnerdal B, Ruel MT, Sandtrom B, Wasantwisut E, Hotz C. International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull. 2004 Mar;25(1 Suppl 2):S99-203. No abstract available.

  PMID: 18046856 BACKGROUND

• Liu Z, Diana A, Slater C, Preston T, Gibson RS, Houghton L, Duffull SB. Development of a nonlinear hierarchical model to describe the disposition of deuterium in mother-infant pairs to assess exclusive breastfeeding practice. J Pharmacokinet Pharmacodyn. 2019 Feb;46(1):1-13. doi: 10.1007/s10928-018-9613-x. Epub 2018 Nov 14.

  PMID: 30430351 BACKGROUND

• Liu Z, Diana A, Slater C, Preston T, Gibson RS, Houghton L, Duffull SB. Development of a Parsimonious Design for Optimal Classification of Exclusive Breastfeeding. CPT Pharmacometrics Syst Pharmacol. 2019 Aug;8(8):596-605. doi: 10.1002/psp4.12428. Epub 2019 Jul 3.

  PMID: 31215140 BACKGROUND

• Michaelsen KF, Hoppe C, Roos N, Kaestel P, Stougaard M, Lauritzen L, Molgaard C, Girma T, Friis H. Choice of foods and ingredients for moderately malnourished children 6 months to 5 years of age. Food Nutr Bull. 2009 Sep;30(3 Suppl):S343-404. doi: 10.1177/15648265090303S303.

  PMID: 19998864 BACKGROUND

• Rahmannia S, Diana A, Luftimas DE, Gurnida DA, Herawati DMD, Houghton LA, Gibson RS. Poor dietary diversity and low adequacy of micronutrient intakes among rural Indonesian lactating women from Sumedang district, West Java. PLoS One. 2019 Jul 11;14(7):e0219675. doi: 10.1371/journal.pone.0219675. eCollection 2019.

  PMID: 31295313 BACKGROUND

• Schaafsma A, Pakan I, Hofstede GJ, Muskiet FA, Van Der Veer E, De Vries PJ. Mineral, amino acid, and hormonal composition of chicken eggshell powder and the evaluation of its use in human nutrition. Poult Sci. 2000 Dec;79(12):1833-8. doi: 10.1093/ps/79.12.1833.

  PMID: 11194049 BACKGROUND

• Thomson CD. Assessment of requirements for selenium and adequacy of selenium status: a review. Eur J Clin Nutr. 2004 Mar;58(3):391-402. doi: 10.1038/sj.ejcn.1601800.

  PMID: 14985676 BACKGROUND

• Diana A, Rahmannia S, Suhadi YZ, Luftimas DE, Rizqi H, Purnamasari AD, Jihadillah A, Ansari MB, Haq DAZ, Pratiwi AN, Puspita DN, Affandy YIKD, Frampton CMA, Fahmida U, Houghton LA, Gibson RS. Chicken liver and eggshell crackers are a safe and affordable animal source food for overcoming micronutrient deficits during pregnancy and lactation in Indonesia: a double-blind, cluster randomized controlled trial (SISTIK Growth Study). BMC Pregnancy Childbirth. 2025 Aug 6;25(1):817. doi: 10.1186/s12884-025-07899-0.

  PMID: 40770284 DERIVED

• Zuhairini Y, Suryanto AH, Adnani QES, Anshari MB, Rizqi H, Fathonah A, Purnamasari AD, Pangasih AH, Jihadillah A, Puspita DN, Luftimas DE, Rahmannia S, Fahmida U, Gibson R, Diana A. Acceptability trial of local Indonesian snack (SISTIK) enriched with chicken liver and eggshell powder as a potential food to increase micronutrient intakes among women of reproductive age. Wellcome Open Res. 2025 Feb 24;9:550. doi: 10.12688/wellcomeopenres.20292.2. eCollection 2024.

  PMID: 40093311 DERIVED

• Diana A, Rahmannia S, Suhadi YZ, Luftimas DE, Rizqi H, Purnamasari AD, Jihadillah A, Ansari MB, Haq DAZ, Pratiwi AN, Scott S, Hampel D, Allen LH, Haszard JJ, Houghton LA, Gibson RS, Fahmida U. Chicken liver and eggshell crackers as a safe and affordable animal source food for overcoming micronutrient deficits during pregnancy and lactation in Indonesia: a double-blind, randomised placebo-controlled trial (SISTIK Growth Study). Wellcome Open Res. 2022 Jun 9;7:167. doi: 10.12688/wellcomeopenres.17879.1. eCollection 2022.

  PMID: 35865219 DERIVED

Related Links

• International Atomic Energy Agency. Stable isotope technique to assess intake of human milk in breastfed infants. Human Health Series No. 7. Vienna: IAEA, 2010.
• World Health Organization. Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations. Vitamin and Mineral Nutrition Information System. Geneva: WHO, 2011 (WHO/NMH/NHD/MNM/112).

Study Officials

• Aly Diana, PhD

  SEAMEO Regional Centre for Food and Nutrition

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A total of 324 pregnant women will be recruited from 28 clusters (villages) and will be randomised to either intervention or control using a randomized sequence, stratified by villages with \< 100 and ≥ 100 infants using block sizes of 2 and 4. Selected pregnant women from these villages will receive daily interventions in the form of 75 gram food products, made from chicken liver and chicken eggshells (Micronutrient-enriched Crackers/MEC) or placebo. The MEC and placebo will be given from 8-14 weeks gestation to 5 months' post-partum.

Study Record Dates

• First Submitted: September 20, 2020
• First Posted: September 25, 2020
• Study Start: November 11, 2020
• Primary Completion: February 20, 2024
• Study Completion: December 31, 2024
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available after analysis has been finalised (around the end of February 2024) and available for a long term.
• Access Criteria: Data will be shared through open journal repositories; free source data sharing (Open Science Framework); harmonised maternal dietary intake will be available to the Food and Agriculture Organization of the United Nations - Global Individual Food consumption data Tool (FAO/WHO GIFT) platform; shared data available in South East Asia Ministers of Education Organization Regional Centre for Food and Nutrition (SEAMEO RECFON) website and social media; use of MEC permitted for non-commercial purposes under a creative common license.

Locations

ID (1)