Rescuing the Microbiome Effectively With Different Doses of B. Infantis in Infants

Study Overview
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Brief Summary
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The REMEDI Study is a single-center, prospective, double-blind, randomized, placebo-controlled trial of multiple doses of B. infantis EVC001 supplementation in healthy term breastfed infants.

Detailed Description
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Mother-infant dyads will be enrolled when the infant is 2-4 months of age. A 1-week lead-in period will be utilized to collect baseline microbiome samples and for the completion of daily and weekly feeding and health logs. Subjects that meet eligibility criteria on Day 7 will be randomized into 1 of 4 treatment arms. Supplementation will begin on Day 8 and will continue for a total of 28 consecutive days. Subjects will be followed for an additional 4 weeks after the cessation of the supplement. The total duration of the study will be approximately 9 weeks. Infant stool and urine samples, as well as maternal breast milk samples, will be collected on multiple occasions during the study. Mothers will be asked to complete questionnaires and health logs during the course of the study as well.

Official Title
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Rescuing the Microbiome Effectively With Different Doses of B. Infantis in Infants (The REMEDI Study)

Conditions
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Gut Microbiome

Intervention / Treatment
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* Other: B. infantis EVC001
* Other: Lactose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of subjects: Infants: 60 to 125 days old, Mothers: 21 years old and greater Mother-infant dyads who live within a 40-mile radius from the clinical site Infants predominately breastfed with maternal intent to continue exclusive breastfeeding for at least 9 additional weeks Term infants born >37 weeks gestation Healthy infants without medical complications Generally healthy women Mothers who are willing to refrain from feeding their infants infant formula, solid foods, and probiotic or iron supplements (confounding variables of the intestinal microbiome) before the end of the study Exclusion Criteria: Mothers diagnosed with any metabolic, endocrine, liver, or kidney disease, any autoimmune disease, cirrhosis, hepatitis C, HIV, AIDs, cancer, obesity (pre-pregnancy BMI >34.9 kg/m2), Crohn's disease, heart disease, type 1 or type 2 diabetes (type 1 diabetes is acceptable if mother's blood glucose has been well-regulated) Infants born in a multiple birth Infants born with medical complications such as: respiratory distress syndrome or birth defects Infants with any GI tract abnormalities Infants who have taken antibiotics within 4 weeks of enrollment or during the Lead-in Period Infants who have taken iron supplements within 4 weeks of enrollment or during the Lead-in Period Infants who have consumed any infant formula within 4 weeks of enrollment or more than 10 times between birth and enrollment or during the Lead-in Period Infants whose parents plan to feed them any infant formula any time throughout the duration of the study Infants who have consumed any probiotics containing B. infantis since birth Infants who have consumed any Bifidobacterium-containing probiotics within 4 weeks of enrollment or during the Lead-in Period Infants whose parents plan to administer probiotics to them any time throughout the duration of the study (not including the study supplement) Infants who have consumed any solid foods or beverages between birth and enrollment or during the Lead-in Period (liquid medicines, supplements, and sugar water are ok) Infants whose parents plan to feed them solid foods or beverages any time throughout the duration of the study Infants whose mothers have changed their minds about their plans to exclusively breastfeed for at least 8 additional weeks by Day 7 For infants born vaginally, maternal intake of probiotics containing B. infantis during the last trimester of pregnancy Mother-infant dyads who live in more than one location Infants who have been diagnosed with any medical or nutritional condition that would require iron supplementation Mothers who smoked cigarettes during pregnancy, currently smoke, or plan to initiate smoking during the study duration Anyone the investigator feels isn't an applicable subject

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 4 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be enrolled and randomized 1:1:1:1 to the following treatment arms (daily dose of B. infantis EVC001): high dose, medium dose, low dose, and placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High dose B. infantis EVC001<br>10 participants will receive powdered B. infantis EVC001 at a high dose per daily oral feeding | Other: B. infantis EVC001<br>* A once-daily oral feeding of B. infantis EVC001 will be mixed with breast milk and provided to infants for 28 consecutive days.<br>|
| Active Comparator: Medium dose B. infantis EVC001<br>10 participants will receive powdered B. infantis EVC001 at a medium dose per daily oral feeding | Other: B. infantis EVC001<br>* A once-daily oral feeding of B. infantis EVC001 will be mixed with breast milk and provided to infants for 28 consecutive days.<br>|
| Active Comparator: Low dose B. infantis EVC001<br>10 participants will receive powdered B. infantis EVC001 at a low dose per daily oral feeding | Other: B. infantis EVC001<br>* A once-daily oral feeding of B. infantis EVC001 will be mixed with breast milk and provided to infants for 28 consecutive days.<br>|
| Placebo Comparator: Lactose Placebo<br>10 participants will receive powdered lactose per daily oral feeding | Other: Lactose<br>* A once-daily oral feeding of a lactose placebo will be mixed with breast milk and provided to infants for 28 consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal B. infantis levels in infants at 28 days - difference between B. infantis and placebo | The difference in levels of infant fecal B. infantis (as measured by B. infantis qPCR) between B. infantis EVC001 supplementation and placebo supplementation on Day 28. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal B. infantis levels in infants at 28 days - difference between B. infantis doses | The differences between B. infantis EVC001 doses on levels of infant fecal B. infantis (as measured by B. infantis qPCR) on Day 28. | 28 days |