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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Malnutrition

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 167 Days
Maximum Age: 197 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ST-DI (Delayed intervention)<br>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<br>* 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<br>|
| Experimental: LNS-10gM<br>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<br>* 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<br>|
| Experimental: LNS-20gM<br>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<br>* 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<br>|
| Experimental: LNS-20gNoM<br>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<br>* 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<br>|
| Experimental: LNS-40gM<br>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<br>* 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<br>|
| Experimental: LNS-40gNoM<br>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<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in length-for-age Z-score (LAZ, based on WHO 2005 MGRS) between enrollment and 18 months of age |  | Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months) | 
| Incidence of serious adverse events during the study period |  | 12 months after enrollment (age 18 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight-for-age (WAZ) and weight-for-length (WLZ) Z-scores |  | Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months) | 
| Incidence of stunting, underweight, and wasting |  | Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months) | 
| Prevalence of reduced appetite |  | Daily assessment during 12 month supplementation | 
| Energy intake from complementary foods |  | 3 and 9 months after enrollment (age 9 and 15 months) | 
| Incidence of laboratory-confirmed malaria infection |  | 12 months after enrollment (age 18 months) | 
| Incidence of caregiver-reported morbidity |  | Daily assessment during 12 month supplementation | 
| Immune function (measured by humoral immunity towards measles vaccination) |  | 12 months after enrollment (age 18 months) | 
| 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 |  | 12 months after enrollment (age 18 months) | 
| Proportion with anaemia at 18 months of age |  | 12 months after enrollment (age 18 months) | 
| Change in erythrocyte essential fatty acid (EFA) concentration (measured from a subsample of 400 participants) |  | 12 months after enrollment (age 18 months) | 
| Neuro-behavioral development (timing of acquisition of the certain skills and more comprehensive analysis at the age of 18 months) |  | Limited assessment every 4 weeks during the 12 months supplementation, more comprehensive at age 18 months | 
| Incidence of all adverse events during the study period |  | 12 months after enrollment (age 18 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stunting, Growth failure, Malnutrition, Lipid based nutrient supplement, LNS, Prevention, Malawi, Sub-Saharan Africa, Dietary supplementation, Efficacy