title: Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial.
abstract: The development of probiotics as therapies to cure or prevent disease lags far behind that of other investigational medications. Rigorously designed phase I clinical trials are nearly non-existent in the field of probiotic research, which is a contributing factor to this disparity. As a consequence, how to appropriately dose probiotics to study their efficacy is unknown. Herein we propose a novel phase I ascending dose trial of Bifidobacterium longum subsp. infantis (B. infantis) to identify the dose required to produce predominant gut colonisation in healthy breastfed infants at 6 weeks of age.
  
  
  
  This is a parallel-group, placebo-controlled, randomised, double-blind ascending dose phase I clinical trial of dietary supplementation with B. infantis in healthy breastfed infants. The objective is to determine the pharmacologically effective dose (ED) of B. infantis required to produce predominant (>50 %) gut colonisation in breastfed infants at 6 weeks of age. Successively enrolled infant groups will be randomised to receive two doses of either B. infantis or placebo on days 7 and 14 of life. Stool samples will be used to characterise the gut microbiota at increasing doses of B. infantis.
  
  
  
  Probiotic supplementation has shown promising results for the treatment of a variety of ailments, but evidence-based dosing regimes are currently lacking. The ultimate goal of this trial is to establish a recommended starting dose of B. infantis for further efficacy-testing phase II trials designed to evaluate B. infantis for the prevention of atopic dermatitis and food allergies in at-risk children.
  
  
  
  Clinicaltrials.gov # NCT02286999 , date of trial registration 23 October 2014.
authors.affiliation: Department of Dermatology, University of California Davis Medical Center, Sacramento, CA, USA.
authors.forename: Smita
authors.initials: S
authors.lastname: Awasthi
authors.affiliation: Department of Dermatology, University of California Davis Medical Center, Sacramento, CA, USA.
authors.forename: Reason
authors.initials: R
authors.lastname: Wilken
authors.affiliation: Department of Dermatology, University of California Davis Medical Center, Sacramento, CA, USA.
authors.forename: Forum
authors.initials: F
authors.lastname: Patel
authors.affiliation: Department of Food Science & Technology, University of California Davis , Davis, CA, USA.
authors.forename: J Bruce
authors.initials: JB
authors.lastname: German
authors.affiliation: Department of Food Science & Technology, University of California Davis , Davis, CA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Mills
authors.affiliation: Department of Chemistry, University of California Davis , Davis, CA, USA.
authors.forename: Carlito B
authors.initials: CB
authors.lastname: Lebrilla
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, University of California Davis , Davis, CA, USA.
authors.forename: Kyoungmi
authors.initials: K
authors.lastname: Kim
authors.affiliation: Foods for Health Institute, University of California Davis , Davis, CA, USA.
authors.forename: Samara L
authors.initials: SL
authors.lastname: Freeman
authors.affiliation: Foods for Health Institute, University of California Davis , Davis, CA, USA.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Smilowitz
authors.affiliation: Department of Dermatology, Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA.
authors.forename: April W
authors.initials: AW
authors.lastname: Armstrong
authors.affiliation: Department of Dermatology, University of California Davis Medical Center, Sacramento, CA, USA. emaverakis@ucdavis.edu.
authors.forename: Emanual
authors.initials: E
authors.lastname: Maverakis
mesh_terms: D000367:Age Factors; D000070236:Bifidobacterium longum subspecies infantis / Q000254:growth & development*; D001942:Breast Feeding; D002140:California; D002985:Clinical Protocols; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D019936:Probiotics / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
keywords: Atopic dermatitis; Atopy; Bifidobacterium infantis; Dose-escalation; Food allergy; Phase I clinical trial; Probiotic