Efficacy of a Multiple Micronutrient-Fortified Lipid-Based Nutrient Supplement for Children Under Two in Cambodia

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the efficacy of the LNS on children aged 6-17 months in preventing growth faltering and improving micronutrient status. The impact of product will be compared to Corn Soy Blend ++ (CSB++), Sprinkles, and to a control group consuming an unsupplemented diet, which is usually borbor at an early age, and thereafter, family foods.

Detailed Description
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BACKGROUND: In Cambodia, progress in combatting malnutrition has stalled. In 2010, 40% of all children under five (and 49% of 4-5 year-olds) were stunted, 11% were wasted, and 28% were underweight, indicating, respectively, chronic and acute malnutrition, and a combination of the two. Stunting is partially attributed to poor complementary feeding, which remains inadequate for achieving growth outcomes and micronutrient status. Malnutrition can be prevented with supplementary foods. These foods usually contain a source of protein and lipids such as powered milk, soy or peanuts, and multiple micronutrients. They can be prepared as a fortified blended product, such as Corn-Soy Blend++ (CSB++), that is mixed with water to make a porridge, or ready-to-use supplementary foods (RUSFs). The latter are usually lipid-based nutrient supplements (LNSs) which are often pastes such as the peanut-based Plumpy'Nut™. These energy-dense supplementary foods contain both macro and micronutrients and are used to prevent and treat moderate acute malnutrition by promoting improved linear growth, weight gain and micronutrient status among children. Until recently, treatment of moderate acute malnutrition has relied on fortified blended products. The new RUSFs are also proving effective, as they are higher energy and have a longer shelf life, and since they require no preparation, are convenient. Another common nutrition intervention is multiple micronutrient supplements such as Sprinkles. These are individually-packed powders that can be added to food. However, micronutrients are more likely to achieve growth outcomes when they are combined with energy, for example, in lipid-based nutrient supplements and there is no evidence that micronutrient powders alone contribute to growth. Until June 2014, the United Nations World Food Program (WFP) used CSB++ (now called Supercereal Plus) to treat and prevent moderate acute malnutrition in Cambodia. Sprinkles are also being distributed, though not widely, to prevent micronutrient deficiencies. These products that have been recently or are currently used are relatively expensive to procure and ship to Cambodia and in the case of Sprinkles, are not as effective as foods that contain macronutrients. Moreover, CSB++ was not very well accepted in practice, and WFP has phased it out. Therefore, UNICEF and the Cambodian Ministry of Health are looking for a locally-produced product containing macro and micronutrients to prevent growth faltering and improve micronutrient status in Cambodian children. TRIAL DESIGN AND METHODOLOGY: Therefore, this trial will evaluate the efficacy of the LNS on children aged 6-17 months in preventing growth faltering and improving micronutrient statu. The impact of product will be compared to CSB++, Sprinkles, and to a control group. The trial is a prospective, cluster randomised, non-blinded controlled trial among infants 6-17 months of age. The trial aims to establish the superiority of the novel LNS, using CSB++ and Sprinkles as active comparators and the unimproved diet as a control. The allocation ratio is 1:1. The study will take place over 8 months. The study will be conducted in 28 sites in peri-urban Phnom Penh. Infants aged 6-12 months will be recruited. Upon consent and enrolment, baseline data will be collected from the participants. This will include demographics, morbidity, anthropometry (weight, height, mid-upper arm circumference, skinfolds), haematological and stool samples, dietary data (breastfeeding, food frequency and dietary diversity). Data will be collected monthly, and haematological samples will be collected again at endline. Participants will then be provided with a one month supply of the food to which their site has been allocated. Staff will explain how to prepare the food, how often it should be consumed, and who should consume it (i.e. subjects). Participants will be provided with food on a monthly basis. They will continue to consume the food over a six-month period, at which time endline data, including haematological samples, will be collected.

Official Title
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Efficacy of a Locally-Produced Multiple Micronutrient-Fortified Lipid-Based Nutrient Supplement (LNS) for Children Under Two Years in Cambodia

Conditions
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Child Malnutrition

Intervention / Treatment
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* Dietary Supplement: LNS
* Dietary Supplement: Corn-soy blend ++ (CSB++)
* Dietary Supplement: Sprinkles


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 6-12 months Normally nourished or only moderately malnourished (MUAC>115mm, WHZ score>-3) Have not received therapy for acute malnutrition within one month prior to presentation Healthy (no ill-health in past two weeks) Anaemia status - normal, mild or moderate No known food intolerances Informed signed consent of caregiver Caregivers are healthy Exclusion Criteria: Children <6 months or >12mths Severely malnourished (MUAC< 115mm, WHZ score<3, bipedal pitting oedema). Have received therapy for acute malnutrition within one month prior to presentation Any medical complications at the recruitment time or illness requiring referral or clinic visit in past 2 weeks Severe anaemia (Hb<70g/l) Known intolerances No informed signed consent of caregiver

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 Months

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lipid-based nutrient supplement (LNS)<br>LNS added to borbor, eaten over 6 months, age 6-12 months to age 11-17 months | Dietary Supplement: LNS<br>* Compact, paste-filled wafer snack containing fish, rice, soy, mungbeans, oil, sugar and multiple micronutrients<br>|
| Active Comparator: Corn-soy blend ++ (CSB++)<br>CSB++ porridge, eaten over 6 months, age 6-12 months to age 11-17 months | Dietary Supplement: Corn-soy blend ++ (CSB++)<br>* Blended flour containing soy, corn, milk powder, oil, sugar and multiple micronutrients.<br>* Other names: Supercereal Plus;|
| Active Comparator: Sprinkles<br>Sprinkles added to borbor, eaten over 6 months, age 6-12 months to age 11-17 months | Dietary Supplement: Sprinkles<br>* Multiple micronutrient powder packaged in sachet.<br>|
| No Intervention: Control<br>Plain borbor and thereafter family foods, eaten over 6 months, age 6-12 months to age 11-17 months | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutritional status | Weight-for-height (WHZ), length/height-for-age (L/HAZ), and weight-for-age (WAZ) calculated through monthly weight and height measurements | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Triceps, biceps and/or subscapular skinfolds | 6 months | 
| Iron status | Analysis of haemoglobin (g/l), ferritin (µg/l), tranferrin receptor (mg/l), C reactive protein (mg/l), and alpha-1-acid glycoprotein (mg/l) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ready-to-use supplementary food (RUSF), Lipid-based nutrient supplement (LNS), Multiple micronutrients (MMN), Complementary feeding, Home fortification, Efficacy/impact, Infant and young child feeding (IYCF), Cambodia, Cluster randomised controlled trial