| Protocol No: | ECCT/23/03/04 | Date of Protocol: | 12-09-2022 |
| Study Title: |
A Phase 3, randomized, double-blind, placebo-controlled study to evaluate the effect of Bi-26 (strain of Bifidobacterium longum, B. infantis) supplementation versus placebo on weight gain in underweight infants
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| The additional site of Dr Simon Kariuki is being submitted as an amendment. | |
| Study Objectives: | Primary Objective To evaluate the change in weight (standardized for age) of infants receiving Bi-26 Key Secondary Objective To evaluate the change in weight of infants receiving Bi-26 Other Secondary Objectives
Exploratory Objectives
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| Laymans Summary: | Poor countries bear a greater burden of children who are born with a weight that is less than it should be for their age. Poor health in the digestive system (gut) can be caused by a poor balance of good bacteria that are thought to play a role in how nutrients are absorbed in the intestines. Good bacteria in a baby’s gut are important in helping the baby grow, develop normally, and be healthier. One of the bacteria, called B. infantis, that is normally found in babies’ guts makes it easier for the baby to digest their mother’s milk and help keep the baby healthy. Babies who have a weight that is less than it should be for their age have less of the B. infantis bacteria, compared to healthy babies. This may cause poor absorption of these nutrients and can lead to babies not being able to gain weight, leading to them becoming underweight and failing to thrive. Providing a dietary supplement with a specific strain of the bacteria known as EVC001 has been shown to boost the friendly bacteria living in the gut and cause significant changes in the composition of the friendly bacteria and its environment in the gut especially in healthy babies who are breastfed. A small study in Bangladesh tested this strain among babies who were aged between 2 and 6 months and had been admitted to hospital, who were also suffering from severe acute malnutrition. They were given the friendly B. infantis bacteria species as a dietary supplement daily for a period of four weeks. It was found out that this supplementation boosted the friendly bacteria and resulted in the children gaining weight and improving their nutritional weight-for-age Z score (WAZ). We want to study underweight babies who are between 1 and 4 months of age who are in the hospital, to see if they will also gain weight after taking the B. infantis supplement Bi-26. If the results in our study show that the dietary supplements with this friendly bacterial species of B. infantis improves weight gain among underweight children, then it can potentially be used in poor countries as a dietary supplement in babies who are underweight. |
| Abstract of Study: |
Bifidobacteria are gram-positive, heterofermentative, anaerobic bacteria that colonize the newborn gut within the first days and weeks of life. They are often the most abundant bacterial genus in a breast-fed infant’s intestinal flora. B. infantis metabolizes Human milk oligosaccharides (HMOs) and produces short chain fatty acids (SCFA) that are thought to play an important role in nutrition and immune development, stimulating anti-inflammatory and inhibiting pro-inflammatory responses [Halloran 2019; Henrick 2021].
B. infantis Bi-26 strain is a nutritional probiotic intervention that will be evaluated in this trial for its ability to improve weight gain and health outcomes of underweight infants with WAZ <-2 who have been hospitalized with acute illness.
Clinical study data in the United States (US) have shown that B. infantis strain EVC001 colonizes the gut and is associated with significant changes to fecal microbiome composition in healthy breast-fed infants [Frese 2017; Henrick 2019]. Supplementation of B. infantis EVC001 has been associated with a reduction in pro-inflammatory cytokines [Henrick 2019]. Similar observations have been reported for preterm infants given B. infantis EVC001 [Nguyen 2021].
In a pilot trial evaluating B. infantis EVC001 supplementation in Bangladesh in hospitalized 2-to 6-month-old infants with SAM, i.e., weight-for-length z score [WLZ] <-3, researchers observed that daily supplementation with B. infantis for 4 weeks was associated with B. infantis colonization and an increase in WAZ [Barratt 2022].
A number of B. infantis strains, including Bi-26, have been designated as generally recognized as safe (GRAS) based on review by a panel of independent experts in the field. Furthermore, the US Food and Drug Administration (FDA) did not have questions about the GRAS determination of Bi-26 (GRN 985). In the US, the GRAS determination and the FDA no question letter allow the use of Bi-26 under its intended conditions of use (healthy term infants) in infant formula. The strain bearing the GRAS designation can also be used in dietary supplements, including those for infants.
In low-income countries, B. infantis strain Bi-26, evaluated in this study, could potentially be used as a dietary supplement in underweight infants if the safety and efficacy findings of the previous pilot study are confirmed.
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