Development of Shelf-Stable, Locally-Sourced, Microbiota-Directed Complementary Foods for Children With Undernutrition

Study site: The study will be conducted among residents of an under slum community in Baoniabad of Mirpur, one of the 21 administrative units of the nation's capital, Dhaka. Mirpur is selected as the study site because it is inhabited by poor and lower middle-class families, residential and sanitary conditions are typical of any congested urban settlement. Additionally, the investigators have established several field sites in the area and they have ongoing research activities in the community.

Enrollment: A trained Field Research Assistant (FRA) will explain the study in detail, answer any questions from the parent(s), and invite the parent(s) to enrol the child in the study. If the parent(s) are interested to volunteer in the study, the designated staff will proceed to screening and consenting. Screening will consist of a review of the inclusion and exclusion criteria listed above. If the subject is eligible to participate, the process will proceed to consenting consisting of a thorough review of the written consent form in a manner appropriate for the child's parents' literacy level. Prior to signing the consent form, the parents of the participants will have an opportunity to ask any questions about the study. If the FRA determines that participants have demonstrated adequate comprehension of the study, the consent form will be signed by the FRA and the child's parent(s). If the parent(s) are not sufficiently literate to read and/or sign the consent form, consenting and a thumbprint signature will be obtained in the presence of a witness who is not associated with the study. The child's parent(s) will be provided with a copy of the signed consent form.

Children will undergo thorough clinical assessment and laboratory tests (if needed) to exclude any organic diseases or any other causes of secondary malnutrition. Detailed inclusion/exclusion criteria are provided separately below.

At the beginning of the study, information will be collected on the demographic characteristics of the participants (family income, standard/type of housing, family structure, parental education, etc.). FRAs will collect anthropometry data by recording the child's weight using a digital scale with 2 g precision (Seca, model 728, Germany), length (using infantometer, Seca, model 416, Germany), and mid-upper arm circumference (MUAC) to the nearest millimeter (using a non-stretch tape). Collection of anthropometric data will subsequently occur at weekly intervals throughout the study.

Study Design: The study will be 8 weeks in duration and comprise 5 arms, with a minimum of 23 children per arm required to complete the study. Children will be randomly assigned to one of the five arms using a computer generated randomization scheme. Efforts will be made to balance arms with respect to gender. Mothers/primary caregivers will be be advised to maintain their child's current dietary and breastfeeding practices throughout the study. Following a 2-week 'run-in' phase with weekly fecal sample collection and a blood draw, treatment will be initiated. The treatment phase will be for 4 weeks, during which time each test product will be administered at the test center twice daily, separated by at least 6 hours. The amount of each serving actually ingested will be calculated by subtracting the leftover amount from the offered amount. Pre-weighed napkins will be provided; any food that is regurgitated, vomited or spilled will be swabbed, weighed and subtracted from the amount offered. Fecal samples will be collected weekly using established SOPs for rapid cryopreservation. A second blood draw will be performed at the end of the 4-week intervention period. There will be a 2- week post intervention phase during which 2 additional fecal samples will be collected (at the end of weeks 7 and 8) to assess changes in the microbiota that occur after cessation of treatment.