Prevention of Linear Growth Failure in Infants and Young Children With Lipid-based Nutrient Supplements (iLiNS-DOSE) (iLiNS-DOSE)

• ClinicalTrials.gov Identifier: NCT00945698
• Recruitment Status: Completed
• First Posted: July 24, 2009
• Last Update Posted: May 27, 2015
• Sponsor: Tampere University
• Collaborators: University of Malawi College of Medicine; University of California, Davis; Bill and Melinda Gates Foundation
• Information provided by (Responsible Party): Per Ashorn, Tampere University

Study Description

Brief Summary:

The use of lipid-based nutrients (LNS), such as Nutributter or fortified spread (FS), have been associated with improved growth and development outcomes among infants in Ghana and Malawi. Modified versions of such supplements have been developed to improve their nutrient density and quality and to lower their costs. Such modified products have proven acceptable to infants and their guardians in Malawi and Ghana. In the present trial, the investigator aim to identify the lowest growth-promoting daily dose of modified LNS. Additionally, the investigators will test a hypothesis that LNS that does not contain milk promotes growth as well as milk-containing LNS when given for 12 months at a 10-40 g daily dose to 6-18 month old infants in rural Malawi.

Condition or disease	Intervention/treatment	Phase
Malnutrition	Dietary Supplement: Lipid-based nutrient supplement, 10gM; Dietary Supplement: Lipid-based nutrient supplement, 20gM; Dietary Supplement: Lipid-based Nutrient Supplement, 20gNoM; Dietary Supplement: Lipid-based nutrient supplement, 40gM; Dietary Supplement: Lipid-based Nutrient Supplement, 40gNoM; Dietary Supplement: Maize-soy flour	Phase 3

Detailed Description:

Six-month old healthy infants are identified through community surveys in the study area. 1920 infants meeting set criteria are randomised into receiving the following intervention between 6 and 18 months of age: 1) standard treatment from 6-18 months (i.e.no supplements, with delayed intervention between 18-30 months of age (ST-DI), 2) 10 g / day milk-containing LNS (LNS-10gM), 3) 20 g / day milk-containing LNS (LNS-20gM), 4) 20 g / day milk-free LNS (LNS-20gNoM), 5) 40 g / day milk-containing LNS, (LNS-40gM) 6) 40 g / day milk-free LNS (LNS-40gNoM). The families receive the food supplements at 2-weekly intervals and the participants undergo a morbidity evaluation weekly, a limited development assessment at 4-weekly intervals and anthropometric evaluation at 26-week intervals and laboratory analyses at enrollment and at 18 months. Growth outcome analyses are done at 18 and at 42 months of age.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1920 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Two-centre, Randomised, Single-blind, Parallel Group Controlled Trial, Testing the Growth Promoting Effect of Long-term Complementary Feeding of Infants With Different Doses and Formulations of Lipid-based Nutrient Supplements (LNS)
• Study Start Date: November 2009
• Actual Primary Completion Date: August 2012
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
ST-DI (Delayed intervention); 1 kg fortified maize / soy flour (Likuni phala, LP) 2-weekly (71 g / day) between 18 and 30 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Maize-soy flour; No food supplement during the primary trial period (6 to 18 months of age); 1 kg fortified maize / soy flour (Likuni phala, LP) 2-weekly (71 g / day) between 18 and 30 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-10gM; 140 g of milk-containing LNS (LNS-10gM) 2-weekly (10 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based nutrient supplement, 10gM; 140 g of milk-containing LNS (LNS-10gM) 2-weekly (10 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-20gM; 280 g of milk-containing LNS (LNS-20gM) 2-weekly (20 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based nutrient supplement, 20gM; 280 g of milk-containing LNS (LNS-20gM) 2-weekly (20 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-20gNoM; 280 g of milk-free LNS (LNS-20gNoM) 2-weekly (20 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based Nutrient Supplement, 20gNoM; 280 g of milk-free LNS (LNS-20gNoM) 2-weekly (20 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-40gM; 560 g of milk-containing LNS (LNS-40gM) 2-weekly (40 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based nutrient supplement, 40gM; 560 g of milk-containing LNS (LNS-40gM) 2-weekly (40 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-40gNoM; 560 g of milk-free LNS (LNS-40gNoM) 2-weekly (40 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based Nutrient Supplement, 40gNoM; 560 g of milk-free LNS (LNS-40gNoM) 2-weekly (40 g / day) between 6 and 18 months of age; Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

Outcome Measures

Primary Outcome Measures :

1. Change in length-for-age Z-score (LAZ, based on WHO 2005 MGRS) between enrollment and 18 months of age [ Time Frame: Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months) ]
2. Incidence of serious adverse events during the study period [ Time Frame: 12 months after enrollment (age 18 months) ]

Secondary Outcome Measures :

1. Change in weight-for-age (WAZ) and weight-for-length (WLZ) Z-scores [ Time Frame: Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months) ]
2. Incidence of stunting, underweight, and wasting [ Time Frame: Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months) ]
3. Prevalence of reduced appetite [ Time Frame: Daily assessment during 12 month supplementation ]
4. Energy intake from complementary foods [ Time Frame: 3 and 9 months after enrollment (age 9 and 15 months) ]
5. Incidence of laboratory-confirmed malaria infection [ Time Frame: 12 months after enrollment (age 18 months) ]
6. Incidence of caregiver-reported morbidity [ Time Frame: Daily assessment during 12 month supplementation ]
7. Immune function (measured by humoral immunity towards measles vaccination) [ Time Frame: 12 months after enrollment (age 18 months) ]
8. Change in hemoglobin and micronutrient status (iron status, measured by zinc protoporphyrin (ZPP); plasma zinc; plasma vitamin A; B-vitamins and related metabolites; urine iodine [ Time Frame: 12 months after enrollment (age 18 months) ]
9. Proportion with anaemia at 18 months of age [ Time Frame: 12 months after enrollment (age 18 months) ]
10. Change in erythrocyte essential fatty acid (EFA) concentration (measured from a subsample of 400 participants) [ Time Frame: 12 months after enrollment (age 18 months) ]
11. Neuro-behavioral development (timing of acquisition of the certain skills and more comprehensive analysis at the age of 18 months) [ Time Frame: Limited assessment every 4 weeks during the 12 months supplementation, more comprehensive at age 18 months ]
12. Incidence of all adverse events during the study period [ Time Frame: 12 months after enrollment (age 18 months) ]

Eligibility Criteria

• Ages Eligible for Study: 167 Days to 197 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Signed informed consent from at least one guardian
• Age 5.50 months to 6.49 months
• Availability during the period of the study.
• Permanent resident of Mangochi District Hospital or Namwera Health Centre catchment area

Exclusion Criteria:

• Weight for length Z score (WLZ) < -2.0
• Presence of oedema
• Severe anaemia (Hb<50 g / l)
• Severe illness warranting hospital referral
• History of allergy towards peanut
• History of anaphylaxis or serious allergic reaction to any substance, requiring emergency medical care
• Concurrent participation in any other clinical trial

Contacts and Locations

Locations

Malawi

University of Malawi, College of Medicine

Mangochi, Malawi

Sponsors and Collaborators

Tampere University

University of Malawi College of Medicine

University of California, Davis

Bill and Melinda Gates Foundation

Investigators

• Principal Investigator: Per Ashorn, MD, PhD; University of Tampere Medical School
• Principal Investigator: Kenneth Maleta, MBBS, PhD; University of Malawi College of Medicine

More Information

Additional Information:

College of Medicine homepage  Home page for University of Tampere Medical School, Department of International Health 

Publications:

Adu-Afarwuah S, Lartey A, Brown KH, Zlotkin S, Briend A, Dewey KG. Home fortification of complementary foods with micronutrient supplements is well accepted and has positive effects on infant iron status in Ghana. Am J Clin Nutr. 2008 Apr;87(4):929-38.

Phuka JC, Maleta K, Thakwalakwa C, Cheung YB, Briend A, Manary MJ, Ashorn P. Complementary feeding with fortified spread and incidence of severe stunting in 6- to 18-month-old rural Malawians. Arch Pediatr Adolesc Med. 2008 Jul;162(7):619-26. doi: 10.1001/archpedi.162.7.619. Erratum in: Arch Pediatr Adolesc Med. 2008 Oct;162(10):942.

Phuka JC, Maleta K, Thakwalakwa C, Cheung YB, Briend A, Manary MJ, Ashorn P. Postintervention growth of Malawian children who received 12-mo dietary complementation with a lipid-based nutrient supplement or maize-soy flour. Am J Clin Nutr. 2009 Jan;89(1):382-90. doi: 10.3945/ajcn.2008.26483. Epub 2008 Dec 3.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bendabenda J, Patson N, Hallamaa L, Ashorn U, Dewey KG, Ashorn P, Maleta K. Does anthropometric status at 6 months predict the over-dispersion of malaria infections in children aged 6-18 months? A prospective cohort study. Malar J. 2019 Apr 22;18(1):143. doi: 10.1186/s12936-019-2778-y.

Bendabenda J, Patson N, Hallamaa L, Mbotwa J, Mangani C, Phuka J, Prado EL, Cheung YB, Ashorn U, Dewey KG, Ashorn P, Maleta K. The association of malaria morbidity with linear growth, hemoglobin, iron status, and development in young Malawian children: a prospective cohort study. BMC Pediatr. 2018 Dec 28;18(1):396. doi: 10.1186/s12887-018-1378-2.

Kumwenda C, Hemsworth J, Phuka J, Ashorn U, Arimond M, Maleta K, Prado EL, Haskell MJ, Dewey KG, Ashorn P. Association between breast milk intake at 9-10 months of age and growth and development among Malawian young children. Matern Child Nutr. 2018 Jul;14(3):e12582. doi: 10.1111/mcn.12582. Epub 2018 Jan 19.

Adams KP, Ayifah E, Phiri TE, Mridha MK, Adu-Afarwuah S, Arimond M, Arnold CD, Cummins J, Hussain S, Kumwenda C, Matias SL, Ashorn U, Lartey A, Maleta KM, Vosti SA, Dewey KG. Maternal and Child Supplementation with Lipid-Based Nutrient Supplements, but Not Child Supplementation Alone, Decreases Self-Reported Household Food Insecurity in Some Settings. J Nutr. 2017 Dec;147(12):2309-2318. doi: 10.3945/jn.117.257386. Epub 2017 Oct 4.

Prado EL, Abbeddou S, Adu-Afarwuah S, Arimond M, Ashorn P, Ashorn U, Brown KH, Hess SY, Lartey A, Maleta K, Ocansey E, Ouédraogo JB, Phuka J, Somé JW, Vosti SA, Yakes Jimenez E, Dewey KG. Linear Growth and Child Development in Burkina Faso, Ghana, and Malawi. Pediatrics. 2016 Aug;138(2). pii: e20154698. doi: 10.1542/peds.2015-4698.

Bendabenda J, Alho L, Ashorn U, Cheung YB, Dewey KG, Vosti SA, Phuka J, Maleta K, Ashorn P. The effect of providing lipid-based nutrient supplements on morbidity in rural Malawian infants and young children: a randomized controlled trial. Public Health Nutr. 2016 Jul;19(10):1893-903. doi: 10.1017/S1368980016000331. Epub 2016 Mar 9.

Hemsworth J, Kumwenda C, Arimond M, Maleta K, Phuka J, Rehman AM, Vosti SA, Ashorn U, Filteau S, Dewey KG, Ashorn P, Ferguson EL. Lipid-Based Nutrient Supplements Increase Energy and Macronutrient Intakes from Complementary Food among Malawian Infants. J Nutr. 2016 Feb;146(2):326-34. doi: 10.3945/jn.115.215327. Epub 2016 Jan 6.

Maleta KM, Phuka J, Alho L, Cheung YB, Dewey KG, Ashorn U, Phiri N, Phiri TE, Vosti SA, Zeilani M, Kumwenda C, Bendabenda J, Pulakka A, Ashorn P. Provision of 10-40 g/d Lipid-Based Nutrient Supplements from 6 to 18 Months of Age Does Not Prevent Linear Growth Faltering in Malawi. J Nutr. 2015 Aug;145(8):1909-15. doi: 10.3945/jn.114.208181. Epub 2015 Jun 10.

Ashorn U, Alho L, Arimond M, Dewey KG, Maleta K, Phiri N, Phuka J, Vosti SA, Zeilani M, Ashorn P. Malawian Mothers Consider Lipid-Based Nutrient Supplements Acceptable for Children throughout a 1-Year Intervention, but Deviation from User Recommendations Is Common. J Nutr. 2015 Jul;145(7):1588-95. doi: 10.3945/jn.114.209593. Epub 2015 May 20.

Kumwenda C, Dewey KG, Hemsworth J, Ashorn P, Maleta K, Haskell MJ. Lipid-based nutrient supplements do not decrease breast milk intake of Malawian infants. Am J Clin Nutr. 2014 Mar;99(3):617-23. doi: 10.3945/ajcn.113.076588. Epub 2013 Dec 24.

• Responsible Party: Per Ashorn, Professor of International Health, Tampere University
• ClinicalTrials.gov Identifier: NCT00945698
• Other Study ID Numbers: iLiNS-DOSE
• First Posted: July 24, 2009
• Last Update Posted: May 27, 2015
• Last Verified: May 2015

Keywords provided by Per Ashorn, Tampere University:

Stunting; Growth failure; Malnutrition; Lipid based nutrient supplement; LNS; Prevention; Malawi; Sub-Saharan Africa; Dietary supplementation; Efficacy

Additional relevant MeSH terms:

Malnutrition; Nutrition Disorders; Vitamins; Vitamin A; Retinol palmitate; Vaccines; Nutrients; Micronutrients; Growth Substances; Physiological Effects of Drugs; Immunologic Factors; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Anticarcinogenic Agents; Antineoplastic Agents