Effects of Three Feeding Regimens on Recovery of Uncomplicated Severely Acute Malnourished Children

Study Overview
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Brief Summary
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This project aims to assess the efficacy of three options under consideration in India for home management of Severe Acute Malnutrition (SAM). The investigators propose to conduct a multi-center randomized controlled trial to determine the efficacy of two community-supported home-based regimes using centrally or locally produced Ready to Use Therapeutic Foods (RUTF) for recovery from uncomplicated SAM after 16 weeks of management, compared with an augmented home-prepared foods regimen. The trial will enroll 911 children with uncomplicated SAM and will have enough statistical power to detect a 15% or greater difference in recovery rates between either one of the intervention groups compared with comparison group.

Detailed Description
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India accounts for over half the global burden of severe acute malnutrition (SAM) in the world. While it is important to accelerate efforts to prevent SAM, effective management of children suffering from it is critical for reducing child mortality and achieving MDG1 and MDG4. Available evidence mostly from studies in Africa suggest that home based management of uncomplicated SAM with Ready to Use Therapeutic Foods (RUTF) is at least as efficacious as facility-based management and that locally produced RUTF is as efficacious as centrally produced RUTF. More evidence on efficacy and effectiveness of home based management using RUTF is needed to decide if this intervention offers substantial advantages over home-prepared foods in the Indian settings. Additionally, there is a demand to generate evidence of efficacy of locally produced RUTF as compared to that of centrally produced RUTF. These issues can only be resolved through a well designed randomized controlled trial. This project therefore aims to assess the efficacy of three options under consideration in India for home management of SAM. The investigators propose to conduct a multi-center randomized controlled trial to determine the efficacy of two community-supported home-based regimes using centrally or locally produced Ready to Use Therapeutic Foods (RUTF) for recovery from uncomplicated SAM after 16 weeks of management, compared with an augmented home-prepared foods regimen. The trial will enroll 911 children with uncomplicated SAM and will have enough statistical power to detect a 15% or greater difference in recovery rates between either one of the intervention groups compared with the comparison group. Participants: The study will be conducted in three sites - urban slums and resettlement colonies in the national capital region, rural (predominantly tribal) Rajasthan, rural and urban Tamil Nadu. Field workers will survey the study area to measure mid-upper arm circumference (MUAC) in children 6 to 59 months of age and refer children with MUAC less than 13 cm to a study clinic. At the study clinic, anthropometric measurements will be taken and children with weight for height less than -3 SD of the WHO standards or oedema of both feet will be offered participation in the study. Intervention and Comparison Regimes for Home Management of SAM Children randomized to the first intervention arm (Arm 1) will receive a centrally produced RUTF. Children randomized to the second intervention arm (Arm 2) will receive a locally produced RUTF. Children randomized to the comparison group (Arm 3) will receive augmented Home-Prepared Foods. The amount of food advised for each child in all the 3 study arms are calculated to provide 175cal/kg body weight per day. These foods will be given to children from the time of enrollment until recovery (but not beyond 16 weeks). Caregivers of all enrolled children will receive counseling on frequency of feeding, amounts to be fed, encouraging children to continue breastfeeding and good hygiene practices. Additional support through a volunteer from the community will be provided to mothers who give consent, to assist in feeding the child. Management Phases: The management will be in two phases: Treatment Phase: From enrolment until recovery or 16 weeks (whichever is earlier), enrolled children will be provided the foods according to the study group they are randomized to, and counselled on their use. Sustenance Phase: After completion of the treatment phase, children in all arms will be referred to the closest Anganwadi centre from where he/she will access supplementary foods given to children as a part of the ICDS strategy. The sustenance phase will last for 16 weeks after end of treatment phase. Outcomes: A trained and standardized team of field workers will conduct weekly anthropometric measurements and also record morbidity, hospitalizations and deaths from enrolment, weekly till recovery or 16 weeks whichever is earlier. In addition, mortality and hospitalization data will be collected at 16 weeks post treatment phase. The primary outcome will be recovery by 16 weeks after enrollment (defined as achieving weight for height greater than or equal to -2 SD and absence of oedema). Secondary outcomes will include: To compare the weight gain (in grams/kg body weight/day) from enrolment till recovery, or till 16 weeks in those who do not attain recovery, at 16 weeks after recovery. To compare the time required to reach recovery (in weeks). To determine the incidence and prevalence of diarrhea, ARI and fever during the treatment phase To compare the mortality and hospitalizations during the treatment phase, 16 weeks after recovery To compare the perceptions of families, health care providers and ICDS functionaries regarding feasibility of use of the feeding regimens in a sub sample from enrolment tom completion of treatment phase To ascertain factors which affect recovery, at 16 weeks post enrolment in those who do not recover. To compare the perceptions of families regarding Anganwadi centre experience at the end of sustenance phase. To compare the proportion of children with weight for height greater than or equal to -2 SD and absence of oedema feet at 16 weeks after recovery (or 32 weeks after enrolment for those who do not recover) To document the costs of implementing the feeding regimens till end of treatment phase. This will include: Estimation of costs of human resource and other inputs Estimation of household costs Costs per week per child estimated based on total costs and covered population The project has been approved by the National Research Alliance for SAM constituted by the Department of Health and Family Welfare, Department of Health Research and Department of Biotechnology. It will be coordinated by Centre for Health Research and Development-Society for Applied Studies. WHO will provide technical support and monitoring for the study implementation as a response to a request from the Alliance. Oversight to the study will be provided by a Technical Advisory group constituted by the Alliance and a Data Safety Monitoring Board. Clearances have been sought from the state governments of Delhi, Rajasthan and Tamil Nadu.

Official Title
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To Evaluate the Impact of Three Feeding Regimens on the Recovery of Children From Uncomplicated Severe Acute Malnutrition (SAM) in India and to Use the Evidence to Inform National Policy

Conditions
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Uncomplicated Severe Acute Malnutrition

Intervention / Treatment
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* Other: Ready to Use Therapeutic Food-Centrally produced
* Other: Ready to Use Therapeutic Food-Locally produced
* Other: High energy and micronutrient rich foods


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6 to 59 months SAM, defined as Weight for height less than -3 SD of WHO standard or oedema of both feet or both. Exclusion Criteria: Complicated SAM defined as child with SAM having signs of severe illness requiring hospitalization Known allergy to animal milk or peanuts Likely to leave the study area permanently in the next 16 weeks

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RUTF-Centrally produced<br>Ready to Use Therapeutic Food-Centrally produced by an Indian company | Other: Ready to Use Therapeutic Food-Centrally produced<br>* Ready to Use Therapeutic Food-Centrally produced by an Indian company.<br>|
| Experimental: RUTF-Locally produced<br>Ready to Use Therapeutic Food-Locally produced by the study team at each study site | Other: Ready to Use Therapeutic Food-Locally produced<br>* Ready to Use Therapeutic Food prepared by the study team<br>|
| Active Comparator: High energy and micronutrient rich foods<br>High energy and micronutrient rich foods prepared by caregivers at home using ingredients provided to them | Other: High energy and micronutrient rich foods<br>* High energy and micronutrient rich foods prepared by caregivers at home using ingredients provided to them<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery by 16 weeks after enrollment (defined as achieving weight for height greater than or equal to -2 SD and absence of oedema of both feet) |  | Weekly till recovery or 16 weeks after enrollment, whichever is earlier | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality and hospitalizations |  | Weekly till 16 weeks or recovery and at end of sustenance phase | 
| Rate of weight gain (grams/kg body wt/day) |  | From enrollment till recovery or 16 weeks whichever is earlier | 
| Time required to reach recovery |  | From enrollment till recovery or 16 weeks whichever is earlier | 
| Íncidence and prevalence of diarrhea, ARI and fever during treatment phase |  | From enrollment till recovery or 16 weeks whichever is earlier | 
| Proportion of children with weight for height greater than or equal to -2 SD and absence of oedema of feet |  | At the end of sustenance phase | 
| Cost of three feeding regimens |  | Enrollment to end of treatment phase | 
| Feedback from families, health care providers and ICDS functionaries about the feeding regimens regarding perceptions and feasibility of use |  | Enrollment to end study | 
| Factors which affect recovery |  | At 16 weeks post enrolment in those that have not recovered | 
| Perception of families regarding anganwadi centre experiences at the end of sustenance phase |  | from end of treatment phase to end of sustanence phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment, severe acute malnutrition