Clinical trial NCT03994315: The EFFECT Study: Probiotic and HMO Supplementation in Infants
Official title: Exclusively Formula-Fed Infants Effectively Colonizing With B. Infantis EVC001 From Lacto-N-Tetraose Supplementation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infant Gut Microbiome
Lead sponsor: Evolve BioSystems, Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-21
Enrollment: 10
Sex: ALL
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a single-center, prospective, randomized, open-label study of an infant probiotic (B. infantis EVC001) and a prebiotic supplement (LNT) in exclusively formula-fed infants. Nine subjects will be randomized (1:1:1) using sealed envelopes into three treatment arms.
Primary purpose: OTHER

Brief summary: Lacto-N-tetraose (LNT) is a human milk oligosaccharide (HMO) present in human colostrum and milk. HMOs are largely undigestable and have no direct nutritive benefit to the infant, but act as a prebiotic substrate for beneficial bacteria (bifidobacteria, in particular) in the infant gut. Exclusively formula-fed infants lack HMOs in their diet in the absence of naturally occurring HMOs from breast milk. The proposed clinical study will evaluate the ability of a prebiotic supplement (LNT) to initiate intestinal colonization of a probiotic strain (B. infantis EVC001) in exclusively formula-fed infants. B. infantis EVC001 has been shown to be well-tolerated and safely consumed in breastfed infants. This study also aims to evaluate the safety and tolerability of LNT in different doses when consumed daily with B. infantis EVC001.

Detailed description: This study is a single-center, prospective, randomized, open-label study of an infant probiotic (B. infantis EVC001) and a prebiotic supplement (LNT) in exclusively formula-fed infants. Nine subjects will be enrolled into three treatment arms:

* Group 1: 8 x 10\^9 CFU B. infantis + LNT (3 g/L then 8 g/L)
* Group 2: 8 x 10\^9 CFU B. infantis + LNT (6 g/L then 12 g/L)
* Group 3: 8 x 10\^9 CFU B. infantis alone Study staff will be unblinded to the treatment assignments. Infants in all groups will receive a once-daily oral feeding of B. infantis EVC001 (8.0 x 10\^9 CFU) mixed with infant formula for 28 consecutive days. Two of the treatment groups (Group 1 \& Group 2) will also receive two dose-escalated concentrations of the prebiotic supplement (LNT) mixed with their daily infant formula: Group 1 will receive a concentration of 3 g/L for 2 weeks followed by 8 g/L for the next 2 weeks. Group 2 will receive a concentration of 6 g/L for 2 weeks followed by 12 g/L for the next 2 weeks. Infants consuming the LNT will cross over to the higher dose without a washout period in between. All infants will be evaluated for an additional 2 weeks after cessation of the supplement(s). The total duration of the study will be approximately 7 weeks.

Eligibility criteria: Inclusion Criteria:

1. Infant is between 0 and 60 days of life at the time of enrollment
2. Infant is exclusively formula-fed with caregiver intent to continue exclusive formula feeding for the duration of the study (at least 7 weeks)
3. Infant is consuming cow's milk-based formula without probiotics
4. Term infant, born \>37 weeks gestation
5. Infant is healthy and without medical complications
6. Infant's caregivers are willing to refrain from feeding their infant breast milk, solid foods, and non-study probiotics prior to study completion

Exclusion Criteria:

1. Infant was born with medical complications such as respiratory distress syndrome or birth defects
2. Infant has any gastrointestinal tract abnormalities
3. Infant has been diagnosed with failure to thrive
4. Infant has taken oral or IV antibiotics or antifungals within 4 weeks of enrollment or during the Lead-in Period
5. Infant is consuming partially hydrolyzed or extensively hydrolyzed infant formula because of gastrointestinal disturbance or gassiness/fussiness
6. Infant has consumed any breast milk within 7 days of enrollment or during the Lead-in Period
7. Infant has consumed any probiotics containing B. infantis since birth
8. Infant has consumed any Bifidobacterium-containing probiotics within 2 weeks of enrollment or during the Lead-in Period
9. Infant's caregivers plan to feed them any breast milk, solid foods, or non-study probiotics at any time throughout the duration of the study
10. Infant was born in a multiple birth
11. Infant lives in more than one location
12. Any infant who the investigator feels is not an appropriate study participant

Primary outcomes:
measure: B. infantis levels in infant stool
timeFrame: Baseline, Days 1-35, Day 40
Secondary outcomes:
measure: Total infant gut microbiome modulation
timeFrame: Baseline, Days 5, 12, 19, 26, 40
measure: Frequency of adverse events
timeFrame: During supplementation (Day 1 to Day 28) and Post-supplementation (Day 29 to Day 42)
measure: Frequency of gastrointestinal symptoms warranting a doctor's visit
timeFrame: During supplementation (Day 1 to Day 28) and Post-supplementation (Day 29 to Day 42)
measure: Frequency of adverse events resulting in withholding or discontinuing the study products
timeFrame: During supplementation (Day 1 to Day 28)
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Coastal Pediatric Research
state: South Carolina
Study officials:
affiliation: Coastal Pediatric Research
name: Rimon Youssef, MD
role: PRINCIPAL_INVESTIGATOR
References: