Clinical trial NCT00524446: Controlled Trial to Test the Efficacy of Lipid-based Nutrient Supplements to Prevent Severe Stunting Among Infants
Official title: A Single-centre, Randomised, Single-blind, Parallel Group Clinical Trial in Rural Malawi, Testing the Growth Promoting Effect of Long-term Complementary Feeding of Infants With a High-energy, Micronutrient Fortified Spread
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malnutrition
Stunting
Developmental Delay
Keywords: Infant
Sub-Saharan Africa
Complementary feeding
Fortified spread
Lipid-based nutrient supplement
Malnutrition
Stunting
Growth
Morbidity
Development
Haemoglobin
Lead sponsor: Tampere University
Sponsor class: OTHER
Collaborators: name: Kamuzu University of Health Sciences
name: Academy of Finland
name: Foundation for Paediatric Research, Finland
name: Medical Research Fund of the Tampere University Hospital, Finland
First posted: 2007-09-03
Enrollment: 840
Sex: ALL
Minimum age (years): 6
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study tests the hypothesis that infants receiving milk-powder containing fortified spread (lipid-based nutrient supplement) as a complementary food for one year have lower incidence of severe stunting (poor length gain) than infants who are provided with no extra food supplements or maize-soy flour for complementary porridge.

Detailed description: Poor growth and severe childhood stunting is very common in rural Malawi and elsewhere in Sub-Sahara Africa. To date, few interventions have proven successful in promoting linear growth in early childhood. Our preliminary results from Malawi suggest that a year-long daily complementary feeding of infants with a high-energy, micronutrient-fortified spread (FS) may markedly reduce the incidence of severe stunting before the age of 18 months. In the present study the investigators will more carefully analyze the efficacy in linear growth promotion and other health benefits of this product when provided as a complementary food to infants between 6 and 18 months of age.

The study will be conducted in Lungwena area, Mangochi District, rural Malawi. Six-month old healthy infants are identified through community surveys in the study area. 840 infants meeting set criteria are randomized into receiving the following intervention between 6 and 18 months of age: 1) standard treatment ie no extra food supplements (but dietary supplementation between 18 and 30 months of age) (ST-DI, control group), 2), "standard" fortified spread with milk-powder as the protein source (FSm), 3) modified fortified spread with soy-powder as the protein source (FSs), or 4) fortified maize-soy flour (likuni phala, LP). The families receive the food supplements at 2-weekly intervals and the participants undergo an anthropometric and developmental evaluation and laboratory analyses at 12-week intervals. Outcome analyses are done at 18 and at 36 months of age.

The impact of the dietary interventions will be primarily assessed by comparing the incidence of severe stunting in the four study groups. Secondary outcomes include a number of anthropometric variables, morbidity, developmental milestones, and laboratory parameters. The study will also produce descriptive data on possible mechanisms for growth failure among the trial subjects.

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 Lungwena Health Centre or Malindi Hospital catchment area

Exclusion Criteria:

* Existing or imminent severe stunting (HAZ \< -2.8)
* Weight for length (WFH) \< 80% of the reference median or presence of oedema
* 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: Incidence of severe stunting (Length-for-age Z score < -3)
timeFrame: 1 year after enrolment
measure: Incidence of serious and non-serious adverse events
timeFrame: 1 year
Secondary outcomes:
measure: Incidence of moderate or severe stunting (Length-for-age Z-score < -2)
timeFrame: 1 year
measure: Length gain (cm)
timeFrame: 1 year
measure: Weight gain (g)
timeFrame: 1 year
measure: Change in anthropometric indices (Weight-for-age Z-score, Weight-for-length Z-score, Length-for-age Z-score), mid-upper arm circumference and head circumference
timeFrame: 1 year
measure: Incidence of moderate or severe underweight or wasting (Weight-for-age Z-score or Weight-for-length Z-score <-2 / -3 SD units)
timeFrame: 1 year
measure: Blood haemoglobin, serum ferritin, vitamin A, and zinc concentration
timeFrame: 18 months of age
measure: Motor, social, and language development (timing of acquisition of defined skills)
timeFrame: 1 year
measure: Incidence of febrile illnesses and laboratory diagnosed malaria
timeFrame: 1 year
measure: Morbidity for respiratory infections, diarrhea, and other illnesses
timeFrame: 1 year
Other outcomes:
Locations:
city: Mangochi
country: Malawi
facility: College of Medicine, University of Malawi
Study officials:
affiliation: University of Tampere Medical School, Finland
name: Per Ashorn, MD, PhD
role: STUDY_DIRECTOR
affiliation: Kamuzu University of Health Sciences
name: Kenneth Maleta, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Xu G, Davis JC, Goonatilleke E, Smilowitz JT, German JB, Lebrilla CB. Absolute Quantitation of Human Milk Oligosaccharides Reveals Phenotypic Variations during Lactation. J Nutr. 2017 Jan;147(1):117-124. doi: 10.3945/jn.116.238279. Epub 2016 Oct 19.
citation: Aakko J, Grzeskowiak L, Asukas T, Paivansade E, Lehto KM, Fan YM, Mangani C, Maleta K, Ashorn P, Salminen S. Lipid-based Nutrient Supplements Do Not Affect Gut Bifidobacterium Microbiota in Malawian Infants: A Randomized Trial. J Pediatr Gastroenterol Nutr. 2017 Apr;64(4):610-615. doi: 10.1097/MPG.0000000000001333.
citation: Mangani C, Ashorn P, Maleta K, Phuka J, Thakwalakwa C, Dewey K, Manary M, Puumalainen T, Cheung YB. Lipid-based nutrient supplements do not affect the risk of malaria or respiratory morbidity in 6- to 18-month-old Malawian children in a randomized controlled trial. J Nutr. 2014 Nov;144(11):1835-42. doi: 10.3945/jn.114.196139. Epub 2014 Sep 17.
citation: Grzeskowiak L, Collado MC, Mangani C, Maleta K, Laitinen K, Ashorn P, Isolauri E, Salminen S. Distinct gut microbiota in southeastern African and northern European infants. J Pediatr Gastroenterol Nutr. 2012 Jun;54(6):812-6. doi: 10.1097/MPG.0b013e318249039c.