Oropharyngeal Candidiasis (OPC) and S-ECC

Early Childhood Caries Clinical Trial

— Oral-Thrush  

Official title:

Association of Early Candida Infection (Oral Thrush) and Severe Early Childhood Caries (S-ECC)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05761197
• Other study ID #: 851149
• Status: Not yet recruiting
• Start date: July 1, 2024
• Est. completion date: August 31, 2028

Study information

• Verified date: February 2024
• Source: University of Pennsylvania
• Contact: Yuan Liu, DDS, MS, PhD
• Phone: 215-573-6248
• Email: liuyuan1[@]upenn.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The overall objective of this study is to investigate the association of early Candida infection (known as oral thrush or oropharyngeal candidiasis, OPC) in children during the first year of life with the onset and severity of severe early childhood caries (S-ECC).

Description:

The overall goal of this study is to conduct a longitudinal observational study to investigate the association of early OPC with the onset and severity of S-ECC to better understand the role of Candida (particularly C. albicans) in severe childhood caries. The investigators will test the hypothesis that OPC is associated with S-ECC by modifying the plaque microbiota and enhancing virulence in a manner that is conducive to the early development of the disease. For this study, a total of 60 infants (aged 6-15-month-old) with or without a history of OPC in their first year of life will be enrolled, based on the inclusion and exclusion criteria. Subjects will have their medical/dental history reviewed from medical records. At each study visit (Baseline, 6-month, 12-month, 18-month, and 24-month follow-ups), an oral examination including soft tissue and caries exam will be performed by a calibrated evaluator. Dental plaque/oral swab samples will be collected at each study visit. In addition, a comprehensive survey including demographic status, oral hygiene, diet, delivery, and feeding method as well as current medication usage will also be collected.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: August 31, 2028
• Est. primary completion date: August 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 15 Months

Eligibility

Inclusion Criteria:

• Male or female individuals at the age of 6-15-month-old
• Must have at least one fully erupted tooth at baseline visit
• Parent/guardian willing and able to provide informed consent
• With or without a history of OPC (the study team will enroll 30 participants with and 30 participants without a history of OPC)

Exclusion Criteria:

• Presence of a systemic medical condition (e.g. Down syndrome etc.)
• Presence of an orofacial deformity
• Presence of dental caries
• Use of systemic antimicrobial therapy within 30 days of the baseline visit
• Presence of any condition which, in the opinion of the investigator, makes participation in the project not in the individual's best interest.

Related Conditions & MeSH terms

• Candida Infection
• Candidiasis
• Candidiasis, Oral
• Early Childhood Caries
• Infections

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	Children's Hospital of Philadelphia

Country where clinical trial is conducted

United States, 

References & Publications (28)

American Academy on Pediatric Dentistry; American Academy of Pediatrics. Policy on early childhood caries (ECC): classifications, consequences, and preventive strategies. Pediatr Dent. 2008-2009;30(7 Suppl):40-3. No abstract available. — View Citation

Bowen WH, Burne RA, Wu H, Koo H. Oral Biofilms: Pathogens, Matrix, and Polymicrobial Interactions in Microenvironments. Trends Microbiol. 2018 Mar;26(3):229-242. doi: 10.1016/j.tim.2017.09.008. Epub 2017 Oct 30. — View Citation

Broffitt B, Levy SM, Warren J, Cavanaugh JE. Factors associated with surface-level caries incidence in children aged 9 to 13: the Iowa Fluoride Study. J Public Health Dent. 2013 Fall;73(4):304-10. doi: 10.1111/jphd.12028. Epub 2013 Jul 26. — View Citation

de Carvalho FG, Silva DS, Hebling J, Spolidorio LC, Spolidorio DM. Presence of mutans streptococci and Candida spp. in dental plaque/dentine of carious teeth and early childhood caries. Arch Oral Biol. 2006 Nov;51(11):1024-8. doi: 10.1016/j.archoralbio.2006.06.001. Epub 2006 Aug 7. — View Citation

Drury TF, Horowitz AM, Ismail AI, Maertens MP, Rozier RG, Selwitz RH. Diagnosing and reporting early childhood caries for research purposes. A report of a workshop sponsored by the National Institute of Dental and Craniofacial Research, the Health Resources and Services Administration, and the Health Care Financing Administration. J Public Health Dent. 1999 Summer;59(3):192-7. doi: 10.1111/j.1752-7325.1999.tb03268.x. No abstract available. — View Citation

Duangthip D, D D. Early childhood caries and candida albicans. Evid Based Dent. 2018 Dec;19(4):100-101. doi: 10.1038/sj.ebd.6401337. Erratum In: Evid Based Dent. 2019 Mar;20(1):13. D, Duangthip [corrected to Duangthip D]. — View Citation

Falsetta ML, Klein MI, Colonne PM, Scott-Anne K, Gregoire S, Pai CH, Gonzalez-Begne M, Watson G, Krysan DJ, Bowen WH, Koo H. Symbiotic relationship between Streptococcus mutans and Candida albicans synergizes virulence of plaque biofilms in vivo. Infect Immun. 2014 May;82(5):1968-81. doi: 10.1128/IAI.00087-14. Epub 2014 Feb 24. — View Citation

GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017 Sep 16;390(10100):1211-1259. doi: 10.1016/S0140-6736(17)32154-2. Erratum In: Lancet. 2017 Oct 28;390(10106):e38. — View Citation

Gugnani N, Pandit IK, Srivastava N, Gupta M, Sharma M. International Caries Detection and Assessment System (ICDAS): A New Concept. Int J Clin Pediatr Dent. 2011 May-Aug;4(2):93-100. doi: 10.5005/jp-journals-10005-1089. Epub 2010 Apr 15. — View Citation

Hajishengallis E, Forrest CB, Koo H. Early Childhood Caries: Future Perspectives in Risk Assessment. JDR Clin Trans Res. 2016 Jul;1(2):110-111. doi: 10.1177/2380084416637577. Epub 2016 Mar 7. No abstract available. — View Citation

Hajishengallis E, Parsaei Y, Klein MI, Koo H. Advances in the microbial etiology and pathogenesis of early childhood caries. Mol Oral Microbiol. 2017 Feb;32(1):24-34. doi: 10.1111/omi.12152. Epub 2016 Feb 4. — View Citation

Hedrick VE, Comber DL, Estabrooks PA, Savla J, Davy BM. The beverage intake questionnaire: determining initial validity and reliability. J Am Diet Assoc. 2010 Aug;110(8):1227-32. doi: 10.1016/j.jada.2010.05.005. — View Citation

Hwang G, Liu Y, Kim D, Li Y, Krysan DJ, Koo H. Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo. PLoS Pathog. 2017 Jun 15;13(6):e1006407. doi: 10.1371/journal.ppat.1006407. eCollection 2017 Jun. — View Citation

Jean J, Goldberg S, Khare R, Bailey LC, Forrest CB, Hajishengallis E, Koo H. Retrospective Analysis of Candida-related Conditions in Infancy and Early Childhood Caries. Pediatr Dent. 2018 Mar 15;40(2):131-135. — View Citation

Kassebaum NJ, Smith AGC, Bernabe E, Fleming TD, Reynolds AE, Vos T, Murray CJL, Marcenes W; GBD 2015 Oral Health Collaborators. Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990-2015: A Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors. J Dent Res. 2017 Apr;96(4):380-387. doi: 10.1177/0022034517693566. — View Citation

Kim D, Sengupta A, Niepa TH, Lee BH, Weljie A, Freitas-Blanco VS, Murata RM, Stebe KJ, Lee D, Koo H. Candida albicans stimulates Streptococcus mutans microcolony development via cross-kingdom biofilm-derived metabolites. Sci Rep. 2017 Jan 30;7:41332. doi: 10.1038/srep41332. — View Citation

Kim HE, Liu Y, Dhall A, Bawazir M, Koo H, Hwang G. Synergism of Streptococcus mutans and Candida albicans Reinforces Biofilm Maturation and Acidogenicity in Saliva: An In Vitro Study. Front Cell Infect Microbiol. 2021 Feb 19;10:623980. doi: 10.3389/fcimb.2020.623980. eCollection 2020. — View Citation

Koo H, Andes DR, Krysan DJ. Candida-streptococcal interactions in biofilm-associated oral diseases. PLoS Pathog. 2018 Dec 13;14(12):e1007342. doi: 10.1371/journal.ppat.1007342. eCollection 2018 Dec. No abstract available. — View Citation

Koo H, Bowen WH. Candida albicans and Streptococcus mutans: a potential synergistic alliance to cause virulent tooth decay in children. Future Microbiol. 2014;9(12):1295-7. doi: 10.2217/fmb.14.92. No abstract available. — View Citation

Kressin NR, Nunn ME, Singh H, Orner MB, Pbert L, Hayes C, Culler C, Glicken SR, Palfrey S, Geltman PL, Cadoret C, Henshaw MM. Pediatric clinicians can help reduce rates of early childhood caries: effects of a practice based intervention. Med Care. 2009 Nov;47(11):1121-8. doi: 10.1097/MLR.0b013e3181b58867. — View Citation

Metwalli KH, Khan SA, Krom BP, Jabra-Rizk MA. Streptococcus mutans, Candida albicans, and the human mouth: a sticky situation. PLoS Pathog. 2013;9(10):e1003616. doi: 10.1371/journal.ppat.1003616. Epub 2013 Oct 17. No abstract available. — View Citation

Policy on Early Childhood Caries (ECC): Classifications, Consequences, and Preventive Strategies. Pediatr Dent. 2016 Oct;38(6):52-54. No abstract available. — View Citation

Qiu R, Li W, Lin Y, Yu D, Zhao W. Genotypic diversity and cariogenicity of Candida albicans from children with early childhood caries and caries-free children. BMC Oral Health. 2015 Nov 17;15(1):144. doi: 10.1186/s12903-015-0134-3. — View Citation

Raja M, Hannan A, Ali K. Association of oral candidal carriage with dental caries in children. Caries Res. 2010;44(3):272-6. doi: 10.1159/000314675. Epub 2010 May 27. — View Citation

Shoaib L, Deery C, Ricketts DN, Nugent ZJ. Validity and reproducibility of ICDAS II in primary teeth. Caries Res. 2009;43(6):442-8. doi: 10.1159/000258551. Epub 2009 Nov 12. — View Citation

Xiao J, Huang X, Alkhers N, Alzamil H, Alzoubi S, Wu TT, Castillo DA, Campbell F, Davis J, Herzog K, Billings R, Kopycka-Kedzierawski DT, Hajishengallis E, Koo H. Candida albicans and Early Childhood Caries: A Systematic Review and Meta-Analysis. Caries Res. 2018;52(1-2):102-112. doi: 10.1159/000481833. Epub 2017 Dec 21. — View Citation

Xiao J, Moon Y, Li L, Rustchenko E, Wakabayashi H, Zhao X, Feng C, Gill SR, McLaren S, Malmstrom H, Ren Y, Quivey R, Koo H, Kopycka-Kedzierawski DT. Candida albicans Carriage in Children with Severe Early Childhood Caries (S-ECC) and Maternal Relatedness. PLoS One. 2016 Oct 14;11(10):e0164242. doi: 10.1371/journal.pone.0164242. eCollection 2016. — View Citation

Yang XQ, Zhang Q, Lu LY, Yang R, Liu Y, Zou J. Genotypic distribution of Candida albicans in dental biofilm of Chinese children associated with severe early childhood caries. Arch Oral Biol. 2012 Aug;57(8):1048-53. doi: 10.1016/j.archoralbio.2012.05.012. Epub 2012 Jun 18. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To study the role of Candida on biofilm cariogenic properties	Candida-bacterial interaction in modulating biofilm development and virulence will be evaluated using validated experimental models	24 months
Primary	To explore the association between OPC and S-ECC onset and severity	Caries will be measured by ICDAS scoring system; Plaque and oral swab samples will be collected at each study visit (Baseline, 6-month, 12-month,18-month and 24-month follow-ups); Candida strains will be detected using culturing-dependent and -independent sequencing techniques.	24 months
Secondary	To evaluate the influence of OPC on the oral microbiota	Microbiome profiling will be done by shot gun sequencing	24 months

External Links

•   AAPD encourages healthcare providers and caregivers to implement preventive practices that can decrease a child's risks of developing this preventable disease to reduce the burden on the child, the family, and society
•   As dental caries can progress throughout a person's lifetime, understanding caries risk factors unique to specific life phases is important. This study aims to assess caries incidence and risk factors for young adolescents.
•   As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016
•   Children with oral C. albicans have higher odds of experiencing ECC, compared to children without C. albicans.
•   Clinical data, together with in vivo studies, provide compelling evidence of the importance of cross-kingdom interactions in the severity of mucosal diseases and dental caries.
•   Early childhood caries (ECC) is a serious and preventable disease which pediatric clinicians can help address by counseling to reduce risk.
•   Early identification and early application of preventive measures are essential to help eliminate this costly and painful disease
•   Enhanced understanding of GtfB-Candida interactions may provide new perspectives for devising effective therapies to disrupt this cross-kingdom relationship associated with an important childhood oral disease.
•   In this study, the authors investigate the presence and genotypic distribution of C. albicans in the dental biofilm of Chinese children with severe early childhood caries (S-ECC).
•   The aim of this in vitro study was to assess the validity and reproducibility of the ICDAS II (International Caries Detection and Assessment System) criteria in primary teeth.
•   The American Academy of Pediatric Dentistry (AAPD) encourages healthcare providers and caregivers to implement preventive practices that can decrease a child's risks of developing this disease.
•   The article discusses recent advances in the role of the biofilm matrix and interactions between opportunistic pathogens and commensals in the pathogenesis of dental caries.
•   The authors provide feasible data to support the clinical findings in regards to the synergistic association between S. mutans and C. albicans in the pathogenesis of ECC.
•   The authors suggest the need to explore how Candida infection is acquired and whether some strains are more infectious than others.
•   The Global Burden of Disease 2015 study aims to use all available data of sufficient quality to generate reliable and valid prevalence, incidence, and disability-adjusted life year (DALY) estimates of oral conditions for the period of 1990 to 2015.
•   The goal of this study was to examine the C. albicans carriage in children with severe early childhood caries (S-ECC) and the maternal relatedness.
•   The ICDAS criteria was developed by an international team of caries researchers to integrate several new criteria systems into one standard system for caries detection and assessment.
•   The presence of C. albicans in the oral environment can now be considered an additional factor that needs to be taken into account in evaluating risks to caries
•   The purpose of this cross-sectional investigation was to determine the validity and reliability of a self-administered beverage intake questionnaire (BEVQ) that estimates mean daily intake of beverages consumed across 19 beverage categories.
•   The purpose of this study was to assess whether there is an association between oral thrush or other Candida-related conditions in infancy and early childhood caries (ECC) diagnosed by pediatricians.
•   The workshop's goal was to review current methods of diagnosis of dental caries in primary teeth and to propose case definitions and diagnostic criteria for future research projects regarding dental caries in preschool-aged children.
•   This review provides a broader perspective about the etiology and pathogenesis of ECC based on previous and current knowledge on biofilm matrix, microbial diversity
•   This study aimed to explore the genotypic diversity and cariogenicity of C. albicans from children with early childhood caries and caries-free children.
•   This study determined the presence of mutans streptococci and Candida spp. in supragingival dental plaque and infected dentine of caries-free children, with early childhood caries and caries
•   This study was carried out to identify association between oral candidal carriage in children and dental caries.
•   This study was conducted to investigate how microbial products from this cross-kingdom association modulate S. mutans build-up in biofilms.
•   This systematic review indicates that children with oral C. albicans have >5 times higher odds of having ECC compared to those without C. albicans.
•   Using a rodent model, the authors explored the implications of the cross-kingdom interaction for the pathogenesis of dental caries.