Survey of the Facial Bacteriome

• ClinicalTrials.gov Identifier: NCT04180748
• Recruitment Status: Recruiting
• First Posted: November 29, 2019
• Last Update Posted: March 26, 2020
• Sponsor: University Health Network, Toronto
• Information provided by (Responsible Party): University Health Network, Toronto

Tracking Information

• First Submitted Date: November 21, 2019
• First Posted Date: November 29, 2019
• Last Update Posted Date: March 26, 2020
• Actual Study Start Date: November 25, 2019
• Estimated Primary Completion Date: May 15, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 25, 2019)

• Bacterial diversity between individuals of each skin condition (i.e. normal, dry, oily, combination, sensitive). (Number of CFU) [ Time Frame: February 2020 ]
  Frequency of unique colonies identified from microbiological and microbiome techniques between individuals of each skin condition (i.e. normal, dry, oily, combination, sensitive).
• Bacterial density (CFU/cm2) between individuals of each skin condition [ Time Frame: February 2020 ]
  Abundance of bacterial colonies per cm2 of sampled area identified from microbiological and microbiome techniques between individuals of each skin condition (i.e. normal, dry, oily, combination, sensitive).
• MolecuLight i:X detection of density and diversity (green or red fluroescence/cm2) [ Time Frame: February 2020 ]
  Abundance of green and/or red fluorescent detection with MolecuLight i:X per cm2 of sampled area between individuals of each skin condition. Frequency of green or red fluorescence per sample.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 25, 2019)

• Identification of spatial distribution of bacterial species (CFU/cm2 of individual species) [ Time Frame: February 2020 ]
  Abundance of unique species and bacterial families identified from microbiological and microbiome techniques between individuals of each skin condition (i.e. normal, dry, oily, combination, sensitive) and Fitzpatrick skin type per. Distribution of unique species and bacterial families across the area of sampling of individuals on Tegaderm "map".
• Identification of spatial distribution of red/green fluorescence detected with MolecuLight i:X™ (red and green fluroescence/cm2) [ Time Frame: February 2020 ]
  Abundance of unique fluorescent (green and red) detection with MolecuLight i:X™ between individuals of each skin condition (i.e. normal, dry, oily, combination, sensitive) and Fitzpatrick skin type. Distribution of red and green fluorescent signals across the area of sampling of individuals on Tegaderm "map".

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: November 25, 2019)

• Imapact of cosmetic use on diversity of bacterial species across individuals with different cosmetic use (high, mid, low). (Number of CFU) [ Time Frame: February 2020 ]
  Compare the frequency of specific bacterial species and bacterial families identified with microbiology and microbiome techniques between individuals with different skin care routines.
• Imapact of cosmetic use on density of bacterial species across individuals with different cosmetic use (high, mid, low). (CFU/cm2) [ Time Frame: February 2020 ]
  Compare the abundance of specific bacterial species and bacterial families identified with microbiology and microbiome techniques between individuals with different skin care routines per cm2 of area sampled.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Survey of the Facial Bacteriome
• Official Title: Survey of Diversity and Density on the Facial Bacteriome of Different Skin Types

Brief Summary

The microbiome can affect skin health from the gut-skin axis, from environmental exposure, and topical treatments. Decreasing biodiversity of skin microbiota has been linked to inflammatory conditions, allergies, and skin health.

This cross sectional study will be used to survey healthy volunteers and measure the density and diversity of skin flora of varying skin types. The aim of this study is to identify associations between the skin flora and characteristics of healthy skin types.

Detailed Description

The microbiome can affect skin health from the gut-skin axis, from environmental exposure, and topical treatments. Decreasing biodiversity of skin microbiota has been linked to inflammatory conditions, allergies and skin health.

Therefore, this cross sectional study will be used to survey healthy volunteers and measure the density and diversity of skin flora of varying skin types.

This study will aim to determine if there are associations between the diversity and/or density of normal bacterial flora and (1) the different skin types (i.e. normal, dry, oily, combination, sensitive); (2) the different Fitzpatrick skin types (i.e. ivory; fair or pale; fair to beige with golden undertones; olive or light brown; dark brown; deeply pigmented dark brown to darkest brown): (3) the number of skin products used daily representing time spent on skin health (i.e. low:0-1, mid:2-4, high:5+). Participants will complete a survey in which they will identify their skin conditions and the number and type of skin products they use on their face as a part of their daily routine.

In addition, this study will evaluate the potential of an autofluorescence image-guided device to capture differences in healthy human skin flora through autofluorescence. The MolecuLight i:X™ is used to detect bacteria in chronic wounds. Based on extensive preclinical and clinical studies, the i:X has demonstrated its capability at collecting autofluorescent images of wounds and detecting the presence and relative changes in connective tissue (e.g. collagen) content and bio-distribution involved in wound healing. It can also detect the presence and relative amounts of commensal and pathogenic bacteria within the wound based on autofluorescence alone (these bacteria are invisible to standard visualization with the naked eye using white light), thus providing a measure of infection status.

The imaging device will be used to image skin from the cheek and forehead of healthy volunteers to compare the fluorescent characteristics of normal skin flora. The fluorescent images captured with the i:X™ will be compared against 16S RNA analysis of the skin microbiome and traditional microbiology techniques with selective and differential tests. In addition, non-selective agars will be used to grow bacteria according to the spatial topography of the skin, using a tape stripping method, with lightly adhesive 3M™Tegaderm wound dressings. This will serve as a "map" for fluorescent images by which to compare fluorescent features to bacterial species.

• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: The study population will consist of healthy volunteers with no existing or recent skin conditions.

Condition

• Understanding Skin Health and the Microbiome
• Microbial Colonization

Intervention

Other: fluorescence imaging with 405nm light

Each group will have images taken with an Health Canada approved device to capture images under white light and 405nm fluorescence with an mCherry filter. These images will not be used for diagnostics and will be analyzed for features which correlate to identified microbes from 16S RNA analysis and traditional microbiological technique. Groups are self identified by participants in order to capture a diverse population.

Study Groups/Cohorts

• Normal skin
  Intervention: Other: fluorescence imaging with 405nm light
• Oily skin
  Intervention: Other: fluorescence imaging with 405nm light
• Dry skin
  Intervention: Other: fluorescence imaging with 405nm light
• Combination skin
  Intervention: Other: fluorescence imaging with 405nm light
• Sensitive skin
  Intervention: Other: fluorescence imaging with 405nm light

Publications *

• Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Doré J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J; MetaHIT Consortium, Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010 Mar 4;464(7285):59-65. doi: 10.1038/nature08821.
• Luckey TD. Introduction to intestinal microecology. Am J Clin Nutr. 1972 Dec;25(12):1292-4.
• Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016 Aug 19;14(8):e1002533. doi: 10.1371/journal.pbio.1002533. eCollection 2016 Aug.
• Burne RA, Quivey RG Jr, Marquis RE. Physiologic homeostasis and stress responses in oral biofilms. Methods Enzymol. 1999;310:441-60. Review.
• Robinson CJ, Bohannan BJ, Young VB. From structure to function: the ecology of host-associated microbial communities. Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76. doi: 10.1128/MMBR.00014-10. Review.
• Davey ME, O'toole GA. Microbial biofilms: from ecology to molecular genetics. Microbiol Mol Biol Rev. 2000 Dec;64(4):847-67. Review.
• Salem I, Ramser A, Isham N, Ghannoum MA. The Gut Microbiome as a Major Regulator of the Gut-Skin Axis. Front Microbiol. 2018 Jul 10;9:1459. doi: 10.3389/fmicb.2018.01459. eCollection 2018. Review.
• Prescott SL, Larcombe DL, Logan AC, West C, Burks W, Caraballo L, Levin M, Etten EV, Horwitz P, Kozyrskyj A, Campbell DE. The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming. World Allergy Organ J. 2017 Aug 22;10(1):29. doi: 10.1186/s40413-017-0160-5. eCollection 2017. Review.
• Lee HJ, Jeong SE, Lee S, Kim S, Han H, Jeon CO. Effects of cosmetics on the skin microbiome of facial cheeks with different hydration levels. Microbiologyopen. 2018 Apr;7(2):e00557. doi: 10.1002/mbo3.557. Epub 2017 Nov 29.
• Sohn E. Skin microbiota's community effort. Nature. 2018 Nov;563(7732):S91-S93. doi: 10.1038/d41586-018-07432-8.
• Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol. 1988 Jun;124(6):869-71.
• Stone FM, Coulter CB. PORPHYRIN COMPOUNDS DERIVED FROM BACTERIA. J Gen Physiol. 1932 Jul 20;15(6):629-39.
• Philipp-Dormston WK, Doss M. Comparison of porphyrin and heme biosynthesis in various heterotrophic bacteria. Enzyme. 1973;16(1):57-64.
• Kjeldstad B, Christensen T, Johnsson A. Porphyrin photosensitization of bacteria. Adv Exp Med Biol. 1985;193:155-9.
• Cox CD, Adams P. Siderophore activity of pyoverdin for Pseudomonas aeruginosa. Infect Immun. 1985 Apr;48(1):130-8.
• Cody YS, Gross DC. Characterization of Pyoverdin(pss), the Fluorescent Siderophore Produced by Pseudomonas syringae pv. syringae. Appl Environ Microbiol. 1987 May;53(5):928-34.
• Agren MS, Werthén M. The extracellular matrix in wound healing: a closer look at therapeutics for chronic wounds. Int J Low Extrem Wounds. 2007 Jun;6(2):82-97. Review.
• DaCosta RS, Kulbatski I, Lindvere-Teene L, Starr D, Blackmore K, Silver JI, Opoku J, Wu YC, Medeiros PJ, Xu W, Xu L, Wilson BC, Rosen C, Linden R. Point-of-care autofluorescence imaging for real-time sampling and treatment guidance of bioburden in chronic wounds: first-in-human results. PLoS One. 2015 Mar 19;10(3):e0116623. doi: 10.1371/journal.pone.0116623. eCollection 2015.
• Wu YC, Kulbatski I, Medeiros PJ, Maeda A, Bu J, Xu L, Chen Y, DaCosta RS. Autofluorescence imaging device for real-time detection and tracking of pathogenic bacteria in a mouse skin wound model: preclinical feasibility studies. J Biomed Opt. 2014 Aug;19(8):085002. doi: 10.1117/1.JBO.19.8.085002.
• He SY, McCulloch CE, Boscardin WJ, Chren MM, Linos E, Arron ST. Self-reported pigmentary phenotypes and race are significant but incomplete predictors of Fitzpatrick skin phototype in an ethnically diverse population. J Am Acad Dermatol. 2014 Oct;71(4):731-7. doi: 10.1016/j.jaad.2014.05.023. Epub 2014 Jun 11.
• Baumann L. Understanding and treating various skin types: the Baumann Skin Type Indicator. Dermatol Clin. 2008 Jul;26(3):359-73, vi. doi: 10.1016/j.det.2008.03.007. Review.
• Ottolino-Perry K, Chamma E, Blackmore KM, Lindvere-Teene L, Starr D, Tapang K, Rosen CF, Pitcher B, Panzarella T, Linden R, DaCosta RS. Improved detection of clinically relevant wound bacteria using autofluorescence image-guided sampling in diabetic foot ulcers. Int Wound J. 2017 Oct;14(5):833-841. doi: 10.1111/iwj.12717. Epub 2017 Feb 28.
• Chamma E, Qiu J, Lindvere-Teene L, Blackmore KM, Majeed S, Weersink R, Dickie CI, Griffin AM, Wunder JS, Ferguson PC, DaCosta RS. Optically-tracked handheld fluorescence imaging platform for monitoring skin response in the management of soft tissue sarcoma. J Biomed Opt. 2015 Jul;20(7):076011. doi: 10.1117/1.JBO.20.7.076011.
• Wu YC, Smith M, Chu A, Lindvere-Teene L, Starr D, Tapang K, Shekhman R, Wong O, Linden R, DaCosta RS. Handheld fluorescence imaging device detects subclinical wound infection in an asymptomatic patient with chronic diabetic foot ulcer: a case report. Int Wound J. 2016 Aug;13(4):449-53. doi: 10.1111/iwj.12451. Epub 2015 Apr 22.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 25, 2019): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 15, 2020
• Estimated Primary Completion Date: May 15, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy male or female 18 years or older.
• Able to provide consent
• Identifies as having normal (n=6), oily (n=6), dry (n=6), combination (n=6), and/or sensitive (n=6) skin groups.

Exclusion Criteria:

• Treatment with topical or oral antibiotic(s) or antifungal(s) within 1 month of enrolment
• Diagnosed with chronic conditions (excluding acne and dermatological conditions)
• Treatment for a chronic condition
• Diagnosed with bacterial/fungal infection within 1 month of enrolment
• Treatment with an investigational drug within 1 month of enrolment
• Allergies to antibiotics, antiseptics, tape, or adhesives
• Inability to consent

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Cristiana O'Brien; 4166348754; cristiana.obrien@uhnresearch.ca

Contact: Sara Rapic; sara.rapic@uhnresearch.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT04180748
• Other Study ID Numbers: 19-5749
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: IPD which underlie results may be shared in an academic publication. It is undecided if these results may yield a publication.

• Responsible Party: University Health Network, Toronto
• Study Sponsor: University Health Network, Toronto
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University Health Network, Toronto
• Verification Date: November 2019