Clinical trial NCT00945698: Prevention of Linear Growth Failure in Infants and Young Children With Lipid-based Nutrient Supplements (iLiNS-DOSE)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malnutrition
Keywords: Stunting
Growth failure
Malnutrition
Lipid based nutrient supplement
LNS
Prevention
Malawi
Sub-Saharan Africa
Dietary supplementation
Efficacy
Lead sponsor: Tampere University
Sponsor class: OTHER
Collaborators: name: Kamuzu University of Health Sciences
name: University of California, Davis
name: Bill and Melinda Gates Foundation
First posted: 2009-07-24
Enrollment: 1920
Sex: ALL
Minimum age (years): 167
Maximum age (years): 197
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Change in length-for-age Z-score (LAZ, based on WHO 2005 MGRS) between enrollment and 18 months of age
timeFrame: Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months)
measure: Incidence of serious adverse events during the study period
timeFrame: 12 months after enrollment (age 18 months)
Secondary outcomes:
measure: Change in weight-for-age (WAZ) and weight-for-length (WLZ) Z-scores
timeFrame: Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months)
measure: Incidence of stunting, underweight, and wasting
timeFrame: Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months)
measure: Prevalence of reduced appetite
timeFrame: Daily assessment during 12 month supplementation
measure: Energy intake from complementary foods
timeFrame: 3 and 9 months after enrollment (age 9 and 15 months)
measure: Incidence of laboratory-confirmed malaria infection
timeFrame: 12 months after enrollment (age 18 months)
measure: Incidence of caregiver-reported morbidity
timeFrame: Daily assessment during 12 month supplementation
measure: Immune function (measured by humoral immunity towards measles vaccination)
timeFrame: 12 months after enrollment (age 18 months)
measure: 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
timeFrame: 12 months after enrollment (age 18 months)
measure: Proportion with anaemia at 18 months of age
timeFrame: 12 months after enrollment (age 18 months)
measure: Change in erythrocyte essential fatty acid (EFA) concentration (measured from a subsample of 400 participants)
timeFrame: 12 months after enrollment (age 18 months)
measure: Neuro-behavioral development (timing of acquisition of the certain skills and more comprehensive analysis at the age of 18 months)
timeFrame: Limited assessment every 4 weeks during the 12 months supplementation, more comprehensive at age 18 months
measure: Incidence of all adverse events during the study period
timeFrame: 12 months after enrollment (age 18 months)
Other outcomes:
Locations:
city: Mangochi
country: Malawi
facility: University of Malawi, College of Medicine
Study officials:
affiliation: University of Tampere Medical School
name: Per Ashorn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kamuzu University of Health Sciences
name: Kenneth Maleta, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1093/ajcn/87.4.929.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Prado EL, Abbeddou S, Adu-Afarwuah S, Arimond M, Ashorn P, Ashorn U, Brown KH, Hess SY, Lartey A, Maleta K, Ocansey E, Ouedraogo JB, Phuka J, Some JW, Vosti SA, Yakes Jimenez E, Dewey KG. Linear Growth and Child Development in Burkina Faso, Ghana, and Malawi. Pediatrics. 2016 Aug;138(2):e20154698. doi: 10.1542/peds.2015-4698.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.