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The EFFECT Study: Probiotic and HMO Supplementation in Infants (EFFECT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03994315
Recruitment Status : Completed
First Posted : June 21, 2019
Last Update Posted : July 9, 2020
Sponsor:
Information provided by (Responsible Party):
Evolve BioSystems, Inc.

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.

Condition or disease Intervention/treatment Phase
Infant Gut Microbiome Other: B. infantis EVC001 Other: Lacto-N-tetraose (LNT) Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Exclusively Formula-Fed Infants Effectively Colonizing With B. Infantis EVC001 From Lacto-N-Tetraose Supplementation
Actual Study Start Date : September 12, 2019
Actual Primary Completion Date : March 13, 2020
Actual Study Completion Date : March 13, 2020

Arm Intervention/treatment
Experimental: B. infantis EVC001 + LNT (3 g/L then 8 g/L)
Infants 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. Group 1 [B. infantis + LNT (3 g/L then 8 g/L)] will also receive two dose-escalated concentrations of the prebiotic supplement (LNT) mixed with their infant formula for every formula preparation during the 28-day supplementation period. They will receive a concentration of 3 g/L for 2 weeks followed by 8 g/L for the next 2 weeks, without a washout period in between.
Other: B. infantis EVC001
Bifidobacterium longum subspecies infantis strain EVC001, designated a "Foods for Special Dietary Use" (FSDU)
Other Name: Evivo

Other: Lacto-N-tetraose (LNT)
LNT is a human milk oligosaccharide (HMO) found in human breast milk and is a selective prebiotic for B. infantis.

Experimental: B. infantis EVC001 + LNT (6 g/L then 12 g/L)
Infants 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. Group 2 [B. infantis + LNT (6 g/L then 12 g/L)] will also receive two dose-escalated concentrations of the prebiotic supplement (LNT) mixed with their infant formula for every formula preparation during the 28-day supplementation period. They will receive a concentration of 6 g/L for 2 weeks followed by 12 g/L for the next 2 weeks, without a washout period in between.
Other: B. infantis EVC001
Bifidobacterium longum subspecies infantis strain EVC001, designated a "Foods for Special Dietary Use" (FSDU)
Other Name: Evivo

Other: Lacto-N-tetraose (LNT)
LNT is a human milk oligosaccharide (HMO) found in human breast milk and is a selective prebiotic for B. infantis.

Active Comparator: B. infantis EVC001 alone
Infants 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.
Other: B. infantis EVC001
Bifidobacterium longum subspecies infantis strain EVC001, designated a "Foods for Special Dietary Use" (FSDU)
Other Name: Evivo




Primary Outcome Measures :
  1. B. infantis levels in infant stool [ Time Frame: Baseline, Days 1-35, Day 40 ]
    To evaluate the ability of different doses of a prebiotic supplement (LNT) to initiate intestinal colonization of a probiotic strain (B. infantis EVC001) in exclusively formula-fed infants. DNA will be extracted from stool swab samples and will be used for quantitative PCR to determine levels of B. infantis.


Secondary Outcome Measures :
  1. Total infant gut microbiome modulation [ Time Frame: Baseline, Days 5, 12, 19, 26, 40 ]
    To evaluate the total gut microbiome modulation from supplementation of B. infantis with and without a prebiotic supplement (LNT) in exclusively formula-fed infants. DNA and RNA will be extracted from stool swab samples and will be used for next generation sequencing to determine relative abundance of the most abundant bacterial taxa.

  2. Frequency of adverse events [ Time Frame: During supplementation (Day 1 to Day 28) and Post-supplementation (Day 29 to Day 42) ]
    Frequency of treatment emergent adverse events (TEAEs), serious TEAEs and TEAEs causing premature discontinuation will be provided by treatment group.

  3. Frequency of gastrointestinal symptoms warranting a doctor's visit [ Time Frame: During supplementation (Day 1 to Day 28) and Post-supplementation (Day 29 to Day 42) ]
    Frequency of gastrointestinal symptoms warranting a doctor's visit will be provided by treatment group.

  4. Frequency of adverse events resulting in withholding or discontinuing the study products [ Time Frame: During supplementation (Day 1 to Day 28) ]
    Frequency of adverse events resulting in withholding or discontinuing the study products will be provided by treatment group.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 60 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03994315


Locations
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United States, South Carolina
Coastal Pediatric Research
Charleston, South Carolina, United States, 29414
Sponsors and Collaborators
Evolve BioSystems, Inc.
Investigators
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Principal Investigator: Rimon Youssef, MD Coastal Pediatric Research
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Responsible Party: Evolve BioSystems, Inc.
ClinicalTrials.gov Identifier: NCT03994315    
Other Study ID Numbers: EV-8901
First Posted: June 21, 2019    Key Record Dates
Last Update Posted: July 9, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No