A Clinical Trial of Silver Diamine Fluoride to Arrest Early Childhood Caries in Young Children

NCT04054635 | Completed Results FDA Device

• 1 other identifier: B2019:068
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Silver diamine fluoride (SDF) is an antibiotic liquid that has the potential to arrest Early Childhood Caries in young children and delay treatment until children can be seen in outpatient settings. While SDF received approval for clinical use in Canada in 2017 (i.e. Advantage Arrest TM/38% SDF), there has been little guidance on the frequency and duration of applications. This study evaluates the use of SDF at different frequencies to manage dental caries in young children. Potential oral microbiome changes in children receiving SDF treatments are also studied. The investigators hypothesize that two applications of SDF at different frequencies will yield similar arrest rates, and that SDF negatively influences the population of cariogenic bacteria in the oral microbiome. The investigators propose a randomized clinical trial to study the use of SDF to arrest cavitated lesions in primary teeth at different application regimens. Regimen 1 will be two applications of SDF four months apart. Regimen 2 will be two applications of SDF six months apart. Regimen 3 will be two applications of SDF one month apart. Arrest of caries lesions will be determined by assessing clinical hardness, colour change and size of lesions at baseline, at second visit, and at the final study visit. Children \< 72 months of age with active caries will be recruited from community-based dental clinics or who are currently on a wait list for dental surgery under general anesthesia in Winnipeg, Manitoba. SDF will be applied on the day of recruitment to cavitated lesions involving dentin followed by 5%NaFV. Depending on which frequency regimen children are randomized to, participants will return for a second visit. At the second visit, caries lesions treated with SDF at baseline will be assessed to see if caries is arrested. A second application of SDF will be applied to these initially treated caries lesions followed by 5%NaFV. Participants will return for a third and final study visit according to the schedule of their randomized grouping. Caries lesions previously treated by SDF will be assessed once again. To investigate SDF's influence on the human oral microbiome, children from each regimen will have plaque samples collected. Samples will be obtained prior to SDF application at baseline, at the first follow-up visit, and at the final visit. Following nucleic acid isolation from plaque samples and amplicon sequencing, data analysis will be performed in lab using established methods.

Conditions

Early Childhood Caries

Keywords

silver diamine fluoride; randomized clinical trial; early childhood caries; severe early childhood caries; oral microbiome; treatment; arrest; application; frequency; regimen; cariogenic bacteria; early childhood oral health impact scale; oral health-related quality of of life; caries; oral bacteriome; oral mycobiome; cavitated lesions

Outcome Measures

Primary Outcomes (3)

• Overall Arrest Rates

  Total number of lesions arrested/total number of lesions treated

  8 months, 12 months, and 2 months

• Anterior Teeth Arrest Rates

  Total number of anterior lesions arrested/total number of anterior lesions treated.

  8 months, 12 months, and 2 months

• Posterior Arrest Rates

  Total number of posterior lesions arrested/total number of posterior lesions treated.

  8 months, 12 months, and 2 months

Study Arms (3)

Regimen 1

EXPERIMENTAL

Two applications of silver diamine fluoride (SDF) four months apart, which is the protocol frequency adopted by the Winnipeg Regional Health Authority's (WRHA) Clinical Guideline on SDF.

Device: Silver diamine fluoride

Regimen 2

EXPERIMENTAL

Two applications of silver diamine fluoride (SDF) six months apart, which is the American Dental Association's recommendation for SDF.

Device: Silver diamine fluoride

Regimen 3

EXPERIMENTAL

Two applications of silver diamine fluoride (SDF) one month apart, which is proposed in the American Academy of Pediatric Dentistry's clinical practice guidelines.

Device: Silver diamine fluoride

Interventions

Silver diamine fluoride DEVICE

Antibiotic liquid with anti-caries effects. A non-restorative option to manage cavitated caries lesions. Approved for clinical use in Canada in 2017.

Also known as: Advantage Arrest Silver Diamine Fluoride 38%

Regimen 1; Regimen 2; Regimen 3

Eligibility Criteria

• Age: Up to 72 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Child is \< 72 months of age with early childhood caries (ECC) with active lesions (International Caries Detection and Assessment System codes 5 or 6).
• Child has ≥ 1 primary tooth with caries that is eligible to receive SDF. Eligible primary teeth must: a) have soft cavitated caries lesions extending into dentin; b) the cavitated lesions must allow for direct application of silver diamine fluoride (SDF). Teeth that meet any of the PUFA (pulpal involvement, ulceration, fistula, and abscess) index criteria (i.e. spontaneous pain due to caries, pulp exposure, mobility, signs of pulpal infection such as abscess, fistula, or swelling) will be excluded. However, a child would still be eligible even if they have at least one tooth that meets PUFA criteria, but other eligible teeth with caries do not.

You may not qualify if:

• Child is allergic or has a sensitivity to silver or other heavy metal ions.
• Child has hereditary generalized developmental defects of enamel (e.g. Amelogenesis Imperfecta, Dentinogenesis Imperfecta)
• Child has severe medical problems that limit participation.
• Child requires immediate rehabilitation under general anesthesia (GA) because of severe infection or pain.
• Antibiotic use within the last 2 weeks.

Sponsors & Collaborators

• University of Manitoba: lead
• Children's Hospital Research Institute of Manitoba: collaborator

Study Sites (1)

Children's Hospital Research Institute of Manitoba

Winnipeg, Manitoba, R3E 3P4, Canada

Location

Related Publications (36)

• Policy on Early Childhood Caries (ECC): Classifications, Consequences, and Preventive Strategies. Pediatr Dent. 2017 Sep 15;39(6):59-61. No abstract available.

  PMID: 29179321 BACKGROUND

• Schroth RJ, Levi JA, Sellers EA, Friel J, Kliewer E, Moffatt ME. Vitamin D status of children with severe early childhood caries: a case-control study. BMC Pediatr. 2013 Oct 25;13:174. doi: 10.1186/1471-2431-13-174.

  PMID: 24160554 BACKGROUND

• Schroth RJ, Harrison RL, Moffatt ME. Oral health of indigenous children and the influence of early childhood caries on childhood health and well-being. Pediatr Clin North Am. 2009 Dec;56(6):1481-99. doi: 10.1016/j.pcl.2009.09.010.

  PMID: 19962032 BACKGROUND

• Schroth RJ, Levi J, Kliewer E, Friel J, Moffatt ME. Association between iron status, iron deficiency anaemia, and severe early childhood caries: a case-control study. BMC Pediatr. 2013 Feb 7;13:22. doi: 10.1186/1471-2431-13-22.

  PMID: 23388209 BACKGROUND

• Schroth RJ, Quinonez C, Shwart L, Wagar B. TREATING EARLY CHILDHOOD CARIES UNDER GENERAL ANESTHESIA: A NATIONAL REVIEW OF CANADIAN DATA. J Can Dent Assoc. 2016 Jul;82:g20.

  PMID: 27548666 BACKGROUND

• Schroth RJ, Smith WF. A review of repeat general anesthesia for pediatric dental surgery in Alberta, Canada. Pediatr Dent. 2007 Nov-Dec;29(6):480-7.

  PMID: 18254418 BACKGROUND

• Fisher-Owens SA, Gansky SA, Platt LJ, Weintraub JA, Soobader MJ, Bramlett MD, Newacheck PW. Influences on children's oral health: a conceptual model. Pediatrics. 2007 Sep;120(3):e510-20. doi: 10.1542/peds.2006-3084.

  PMID: 17766495 BACKGROUND

• Selwitz RH, Ismail AI, Pitts NB. Dental caries. Lancet. 2007 Jan 6;369(9555):51-9. doi: 10.1016/S0140-6736(07)60031-2.

  PMID: 17208642 BACKGROUND

• Peng JJ, Botelho MG, Matinlinna JP. Silver compounds used in dentistry for caries management: a review. J Dent. 2012 Jul;40(7):531-41. doi: 10.1016/j.jdent.2012.03.009. Epub 2012 Apr 3.

  PMID: 22484380 BACKGROUND

• Chu CH, Lo EC, Lin HC. Effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting dentin caries in Chinese pre-school children. J Dent Res. 2002 Nov;81(11):767-70. doi: 10.1177/0810767.

  PMID: 12407092 BACKGROUND

• Rosenblatt A, Stamford TC, Niederman R. Silver diamine fluoride: a caries "silver-fluoride bullet". J Dent Res. 2009 Feb;88(2):116-25. doi: 10.1177/0022034508329406.

  PMID: 19278981 BACKGROUND

• Horst JA, Ellenikiotis H, Milgrom PL. UCSF Protocol for Caries Arrest Using Silver Diamine Fluoride: Rationale, Indications and Consent. J Calif Dent Assoc. 2016 Jan;44(1):16-28.

  PMID: 26897901 BACKGROUND

• Milgrom P, Horst JA, Ludwig S, Rothen M, Chaffee BW, Lyalina S, Pollard KS, DeRisi JL, Mancl L. Topical silver diamine fluoride for dental caries arrest in preschool children: A randomized controlled trial and microbiological analysis of caries associated microbes and resistance gene expression. J Dent. 2018 Jan;68:72-78. doi: 10.1016/j.jdent.2017.08.015. Epub 2017 Sep 1.

  PMID: 28866468 BACKGROUND

• Gao SS, Zhao IS, Hiraishi N, Duangthip D, Mei ML, Lo ECM, Chu CH. Clinical Trials of Silver Diamine Fluoride in Arresting Caries among Children: A Systematic Review. JDR Clin Trans Res. 2016 Oct;1(3):201-210. doi: 10.1177/2380084416661474. Epub 2016 Aug 20.

  PMID: 30931743 BACKGROUND

• Slayton RL, Urquhart O, Araujo MWB, Fontana M, Guzman-Armstrong S, Nascimento MM, Novy BB, Tinanoff N, Weyant RJ, Wolff MS, Young DA, Zero DT, Tampi MP, Pilcher L, Banfield L, Carrasco-Labra A. Evidence-based clinical practice guideline on nonrestorative treatments for carious lesions: A report from the American Dental Association. J Am Dent Assoc. 2018 Oct;149(10):837-849.e19. doi: 10.1016/j.adaj.2018.07.002.

  PMID: 30261951 BACKGROUND

• Use of Silver Diamine Fluoride for Dental Caries Management in Children and Adolescents, Including Those with Special Health Care Needs. Pediatr Dent. 2017 Sep 15;39(6):146-155.

  PMID: 29179353 BACKGROUND

• Horst JA. Silver Fluoride as a Treatment for Dental Caries. Adv Dent Res. 2018 Feb;29(1):135-140. doi: 10.1177/0022034517743750.

  PMID: 29355428 BACKGROUND

• Pahel BT, Rozier RG, Slade GD. Parental perceptions of children's oral health: the Early Childhood Oral Health Impact Scale (ECOHIS). Health Qual Life Outcomes. 2007 Jan 30;5:6. doi: 10.1186/1477-7525-5-6.

  PMID: 17263880 BACKGROUND

• Jankauskiene B, Virtanen JI, Kubilius R, Narbutaite J. Oral health-related quality of life after dental general anaesthesia treatment among children: a follow-up study. BMC Oral Health. 2014 Jul 1;14:81. doi: 10.1186/1472-6831-14-81.

  PMID: 24984901 BACKGROUND

• Ward TL, Dominguez-Bello MG, Heisel T, Al-Ghalith G, Knights D, Gale CA. Development of the Human Mycobiome over the First Month of Life and across Body Sites. mSystems. 2018 Mar 6;3(3):e00140-17. doi: 10.1128/mSystems.00140-17. eCollection 2018 May-Jun.

  PMID: 29546248 BACKGROUND

• Walters W, Hyde ER, Berg-Lyons D, Ackermann G, Humphrey G, Parada A, Gilbert JA, Jansson JK, Caporaso JG, Fuhrman JA, Apprill A, Knight R. Improved Bacterial 16S rRNA Gene (V4 and V4-5) and Fungal Internal Transcribed Spacer Marker Gene Primers for Microbial Community Surveys. mSystems. 2015 Dec 22;1(1):e00009-15. doi: 10.1128/mSystems.00009-15. eCollection 2016 Jan-Feb.

  PMID: 27822518 BACKGROUND

• Usyk M, Zolnik CP, Patel H, Levi MH, Burk RD. Novel ITS1 Fungal Primers for Characterization of the Mycobiome. mSphere. 2017 Dec 13;2(6):e00488-17. doi: 10.1128/mSphere.00488-17. eCollection 2017 Nov-Dec.

  PMID: 29242834 BACKGROUND

• Agnello M, Marques J, Cen L, Mittermuller B, Huang A, Chaichanasakul Tran N, Shi W, He X, Schroth RJ. Microbiome Associated with Severe Caries in Canadian First Nations Children. J Dent Res. 2017 Nov;96(12):1378-1385. doi: 10.1177/0022034517718819. Epub 2017 Jul 14.

  PMID: 28709393 BACKGROUND

• Peters BA, Wu J, Hayes RB, Ahn J. The oral fungal mycobiome: characteristics and relation to periodontitis in a pilot study. BMC Microbiol. 2017 Jul 12;17(1):157. doi: 10.1186/s12866-017-1064-9.

  PMID: 28701186 BACKGROUND

• Schroth RJ, Jeal NS, Kliewer E, Sellers EA. The relationship between vitamin D and severe early childhood caries: a pilot study. Int J Vitam Nutr Res. 2012 Feb;82(1):53-62. doi: 10.1024/0300-9831/a000094.

  PMID: 22811377 BACKGROUND

• Davidson K, Schroth RJ, Levi JA, Yaffe AB, Mittermuller BA, Sellers EAC. Higher body mass index associated with severe early childhood caries. BMC Pediatr. 2016 Aug 20;16:137. doi: 10.1186/s12887-016-0679-6.

  PMID: 27543009 BACKGROUND

• Prowse S, Schroth RJ, Wilson A, Edwards JM, Sarson J, Levi JA, Moffatt ME. Diversity considerations for promoting early childhood oral health: a pilot study. Int J Dent. 2014;2014:175084. doi: 10.1155/2014/175084. Epub 2014 Jan 30.

  PMID: 24624141 BACKGROUND

• Schroth RJ, Edwards JM, Brothwell DJ, Yakiwchuk CA, Bertone MF, Mellon B, Ward J, Ellis M, Hai-Santiago K, Lawrence HP, Moffatt ME. Evaluating the impact of a community developed collaborative project for the prevention of early childhood caries: the Healthy Smile Happy Child project. Rural Remote Health. 2015 Oct-Dec;15(4):3566. Epub 2015 Nov 4.

  PMID: 26530126 BACKGROUND

• Macintosh AC, Schroth RJ, Edwards J, Harms L, Mellon B, Moffatt M. The impact of community workshops on improving early childhood oral health knowledge. Pediatr Dent. 2010 Mar-Apr;32(2):110-7.

  PMID: 20483013 BACKGROUND

• Schroth RJ, Moore P, Brothwell DJ. Prevalence of early childhood caries in 4 Manitoba communities. J Can Dent Assoc. 2005 Sep;71(8):567.

  PMID: 16202195 BACKGROUND

• Schroth RJ, Wilson A, Prowse S, et al. Looking back to move forward: understanding service provider, parent, and caregiver views on early childhood oral health promotion in Manitoba, Canada. Can J Dent Hyg. 2014 Jan;48(3):99-108.

  BACKGROUND

• Canadian Institute for Health Information. Treatment of Preventable Dental Cavities in Preschoolers: A Focus on Day Surgery Under General Anesthesia. Ottawa, ON: CIHI; 2013. p. 1-34.

  BACKGROUND

• Sihra R, Schroth RJ, Bertone M, Martin H, Patterson B, Mittermuller BA, Lee V, Patterson B, Moffatt ME, Klus B, Fontana M, Robertson L. The Effectiveness of Silver Diamine Fluoride and Fluoride Varnish in Arresting Caries in Young Children and Associated Oral Health-Related Quality of Life. J Can Dent Assoc. 2020 Jun;86:k9.

  PMID: 32543369 BACKGROUND

• Grant CG, Daymont C, Rodd C, Mittermuller BA, Pierce A, Kennedy T, Singh S, Moffatt MEK, Schroth RJ. Oral Health-Related Quality of Life of Canadian Preschoolers with Severe Caries After Dental Rehabilitation Under General Anesthesia. Pediatr Dent. 2019 May 15;41(3):221-228.

  PMID: 31171075 BACKGROUND

• Manerkar M, de Jesus VC, Mittermuller BA, Lee VHK, Singh S, Bertone M, Chelikani P, Schroth RJ. Effects of silver diamine fluoride on oral bacteriome and mycobiome: a randomized clinical trial. BMC Oral Health. 2025 Oct 21;25(1):1643. doi: 10.1186/s12903-025-06986-0.

  PMID: 41120980 DERIVED

• Schroth RJ, Bajwa S, Lee VHK, Mittermuller BA, Singh S, Cruz de Jesus V, Bertone M, Chelikani P. An open-label, parallel-group, randomized clinical trial of different silver diamine fluoride application intervals to arrest dental caries. BMC Oral Health. 2024 Sep 4;24(1):1036. doi: 10.1186/s12903-024-04791-9.

  PMID: 39227897 DERIVED

MeSH Terms

Conditions

Heart Arrest

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

A limitation of this study is the significant difference in the number of teeth and lesions treated between the three groups. The six-month interval group (regimen 2) had a lower number of lesions treated than the one-month (regimen 3) or four-month (regimen 1) interval groups. Since arrest rates were analyzed using a pooled sample, the six-month interval group may have been disadvantaged from a lack of additional lesions to be examined.

Results Point of Contact

• Title: Dr. Robert J. Schroth
• Organization: University of Manitoba

robert.schroth@umanitoba.ca

204-977-7764

Study Officials

• Robert J Schroth

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants are randomly assigned to one of three application regimens of silver diamine fluoride (SDF) to cavitated caries lesions in primary teeth during the duration of the study. Regimen 1 will be two applications of SDF four months apart. Regimen 2 will be two applications of SDF six months apart. Regimen 3 will be two applications of SDF one month apart.

Study Record Dates

• First Submitted: August 10, 2019
• First Posted: August 13, 2019
• Study Start: October 1, 2019
• Primary Completion: March 5, 2022
• Study Completion: July 31, 2023
• Last Updated: September 13, 2023
• Results First Posted: September 13, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)