Malnutrition in babies younger than 6 months is a serious health problem and puts them at a higher risk of dying than older children. It is usually identified when a baby is much smaller than expected for their age, or if they have swelling in their legs or feet. Malnutrition in these babies can happen because they were born small, often have diarrhea, live with illness or disability, or poor feeding practices especially problems with breastfeeding. Problems with gut bacteria may also make it harder for babies to absorb nutrients properly, making it harder for them to grow and gain weight. Many babies in low- and middle-income countries suffer serious health problems due to malnutrition. This study is testing whether giving two types of helpful bacteria (probiotics), B. infantis and LGG®, every day for 28 days helps underweight babies gain more weight. These probiotics may help babies have less diarrhea and better gut health. They might also help babies use breast milk more effectively, which can support growth and development. Researchers from the Africa Clinical Research Network are working with local scientists to see if find out whether giving these probiotics helps babies gain weight better than a powder with no active ingredients (called a placebo). Around About 200 babies from several countries will take part in this study. KEMRI-Mtwapa site is one of the selected sites that will enroll participants in Kenya. Babies aged between 1 and 4 months will be enrolled and randomly placed into two groups. Each baby will be assessed regularly over a period of about 3 months (about 90 days) to see how they are growing. Some babies will get the probiotic powders, and others will get a powder that doesn’t contain the active ingredients. The powders will be given once a day for 28 days. Researchers hope to confirm that giving these probiotics for 28 days helps underweight babies who were recently sick to gain more weight and improve their overall health.

Considering the large unmet medical need for management of underweight infants, if found to be effective, B. infantis combined with LGG supplementation has the potential to have a large global impact on infant health.

Background

Acute malnutrition is a specific form of undernutrition that is commonly defined as “the combination of wasting and oedematous malnutrition, i.e. swelling of the lower limbs”. Infant malnutrition, including undernutrition, can lead to impaired growth, immune and metabolic dysfunction, increased risk of infection, altered development of the central nervous system, and other abnormalities. Severe acute malnutrition is increasingly being recognized in infants under 6 months of age and is often associated with higher mortality rate in young infants than in older infants and children. This trial evaluates the impact of supplementing underweight infants who were recently hospitalised using 2 probiotics, Bifidobacterium longum subsp. Infantis (Bifin02) and Lacticaseibacillus rhamnosus (LGG). The trial will integrate a within-trial economic evaluation. The economic evaluation will provide critical insights into the financial feasibility and potential health benefits of implementing this intervention on a larger scale and a longer time frame.

Purpose and rationale

This trial evaluates the combined use of Bifin02 and LGG® probiotics to improve weight gain and other health outcomes in underweight infants recently hospitalized in low- and middle- income countries (LMICs), aiming to enhance recovery through complementary gut and growth benefits. The economic evaluation will provide critical insights into the financial feasibility and potential health benefits of implementing this intervention on a larger scale and a longer time frame.

Objective: This is a phase 3, randomized, double-blind, placebo-controlled trial designed to evaluate increased weight gain with, and safety of, co-administration of Bifin02 and LGG®, versus placebo in underweight infants (-4.5 ≤ WAZ < -2.0) recently discharged from the hospital following acute non-surgical illness and to assess the financial practicability of including these probiotic supplementations in regular care.

Methodology

This is a Phase 3, randomized, double-blind, placebo-controlled trial to evaluate increased weight gain with, and safety of, co-administration of Bifin02 and LGG®, versus placebo in underweight infants (-4.5 ≤ WAZ < -2.0) recently discharged from the hospital following an acute non-surgical illness. The participants are expected to be enrolled in 5-10 sites in Kenya and Zimbabwe, with the KEMRI-Mtwapa site being one of the participating sites in Kenya. A sufficient number of participants will be screened to randomize approximately 200 participants across the participating sites and follow-up each participant for 3 months.

Expectation

The expected findings of this trial include confirmation that B. infantis and LGG supplementation for 28 days will lead to increased weight gain in underweight infants (-4.5 ≤ WAZ < -2.0) who were hospitalized with acute non-surgical illness and provide valuable data on the cost-effectiveness of probiotics in Zimbabwe and Kenya.