The Pharmacokinetics of Silver Diamine Fluoride (SDF) in Healthy Children

Dental Caries in Children Clinical Trial

— SDF  

Official title:

The Pharmacokinetics of Silver Diamine Fluoride (SDF) in Healthy Children

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04766775
• Other study ID #: DF CD1914/0065/20157 (P)
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 3, 2020
• Est. completion date: November 26, 2021

Study information

• Verified date: March 2021
• Source: University of Malaya
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study focus on the pharmacokinetic characteristic of silver diamine fluoride (SDF) in healthy children. All of the children received treatment for the decayed teeth in the same way. A medication called silver diamine fluoride is used to treat the decayed teeth. It contains a high concentration of fluoride (range from 14100 ppm to 51013 ppm) and silver. This medication halts the decay process through the combined effects of anti-bacterial from silver and remineralization from fluoride. As this product contains the highest concentration of fluoride level found in the market and the metal element of silver, the investigators aim to study the body's reaction towards SDF. The investigators collect the hair and urine samples at different time points and then analyze them to determine the silver and/or fluoride levels. The outcomes include 1. the silver level in the hair and urine samples 2. the fluoride level in the urine samples. The investigators analyze the silver level in hair and urine samples using Inductively Coupled Plasma Mass Spectrometry (ICP-MS); fluoride level in urine samples using Ion-Selective Electrode.

Description:

This research aims to determine the pharmacokinetics characteristics of silver and fluoride following topical application of Silver Diamine Fluoride (SDF) in healthy children. The use of Silver Diamine Fluoride is increasingly widespread since the device is approved by the Food and Drug Administration (FDA) of the United States in 2014, especially among the pediatric population. It is a single-arm, clinical study with the specific objectives: 1. to assess the level of silver and fluoride in the urine sample of patients receiving the SDF treatment; 2. to evaluate the pharmacokinetics of silver, based on the hair sample of patients receiving the SDF treatment. The investigators hypothesize that the pharmacokinetic characteristics of silver diamine fluoride in healthy children are different from that of silver diamine fluoride in healthy adults. The research is taking place at the Paediatrics Dentistry Specialist Clinic, Faculty of Dentistry, University of Malaya. The investigators have used a convenience sampling method to recruit children aged 4-10 years old to join the study. The investigators have calculated the sample size based on the alpha error probability of 0.05 and the power of study at 95%. The investigators have recruited children with at least one decayed primary tooth without clinical signs or symptoms. Radiographically the deepest layer of caries lesion does not involve the pulp. The investigators have excluded children with known medical illness, having glass ionomer or stainless steel crown restorations in the oral cavity. All of the recruited patients received the same intervention, the application of SDF onto the tooth cavity. The investigators have taken the patients' biological samples (urine and hair) to assess the silver and/or fluoride levels. The urine samples are collected before the SDF treatment, in the first and second 24 hours after the SDF treatment. Besides that, hair samples are collected before the SDF treatment, followed by days 7,14,30,60,75, and 90 after the SDF treatment. The silver level in hair and urine samples were analyzed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS); fluoride level in urine samples using Ion-Selective Electrode. After review at days 90, if caries remains active despite the SDF treatment, the investigators will restore the SDF treated teeth or continue the six-monthly application of SDF depending on the patient's ability to cope with the procedure and the caries status.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: November 26, 2021
• Est. primary completion date: November 26, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 4 Years to 10 Years

Eligibility

Inclusion Criteria:

1. Healthy children aged between 4 to 10 years old

• With at least one decayed primary tooth without clinical signs or symptoms suggesting reversible or irreversible pulpitis.

• Radiographically the deepest layer of caries lesion does not encroach on pulp, and inter-radicular supporting structures appear normal

Exclusion Criteria:

1. Children aged below 4 years and above 10 years

2. Healthy children aged between 4 to 10 years old

• Do not have decayed teeth

• The decayed tooth with clinical signs or symptoms suggesting reversible or irreversible pulpitis

• Radiographically the deepest layer of caries lesion does encroach on pulp, and inter-radicular supporting structures appear abnormal

• No consent and permission to join the study

• Taking medications/over the counter medications/supplements

• Known allergy to silver or fluoride

• Presence of ulcer in the mouth which has not heal completely

• Presence of at least one tooth treated with silver fillings or stainless steel crown.

• Presence of at least one tooth filled with a material that contains glass particles known as glass ionomer within a year before this research.

• Children with medical problems

Related Conditions & MeSH terms

• Dental Caries
• Dental Caries in Children

Intervention

Device:
• Silver Diamine Fluoride
Silver Diamine Fluoride (Riva Star) which contains silver, fluoride, ammonia and water.

Locations

Country	Name	City	State
Malaysia	University of Malaya	Kuala Lumpur	Kuala

Sponsors (1)

Lead Sponsor	Collaborator
University of Malaya

Country where clinical trial is conducted

Malaysia, 

References & Publications (14)

Chen KF, Milgrom P, Lin YS. Silver Diamine Fluoride in Children Using Physiologically Based PK Modeling. J Dent Res. 2020 Jul;99(8):907-913. doi: 10.1177/0022034520917368. Epub 2020 May 6. — View Citation

Cooper GA, Kronstrand R, Kintz P; Society of Hair Testing. Society of Hair Testing guidelines for drug testing in hair. Forensic Sci Int. 2012 May 10;218(1-3):20-4. doi: 10.1016/j.forsciint.2011.10.024. Epub 2011 Nov 15. — View Citation

Crystal YO, Marghalani AA, Ureles SD, Wright JT, Sulyanto R, Divaris K, Fontana M, Graham L. 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(5):135-145. — View Citation

DiVincenzo GD, Giordano CJ, Schriever LS. Biologic monitoring of workers exposed to silver. Int Arch Occup Environ Health. 1985;56(3):207-15. — View Citation

Goullé JP, Mahieu L, Castermant J, Neveu N, Bonneau L, Lainé G, Bouige D, Lacroix C. Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma, urine and hair. Reference values. Forensic Sci Int. 2005 Oct 4;153(1):39-44. — View Citation

Kintz P. Hair Analysis in Forensic Toxicology: An Updated Review with a Special Focus on Pitfalls. Curr Pharm Des. 2017;23(36):5480-5486. doi: 10.2174/1381612823666170929155628. Review. — View Citation

Lansdown AB. Silver in health care: antimicrobial effects and safety in use. Curr Probl Dermatol. 2006;33:17-34. Review. — View Citation

Lansdown AB. Silver. I: Its antibacterial properties and mechanism of action. J Wound Care. 2002 Apr;11(4):125-30. Review. — View Citation

Lin YS, Rothen ML, Milgrom P. Pharmacokinetics of 38% topical silver diamine fluoride in healthy adult volunteers. J Am Dent Assoc. 2019 Mar;150(3):186-192. doi: 10.1016/j.adaj.2018.10.018. — View Citation

Ngara B, Zvada S, Chawana TD, Stray-Pedersen B, Nhachi CFB, Rusakaniko S. A population pharmacokinetic model is beneficial in quantifying hair concentrations of ritonavir-boosted atazanavir: a study of HIV-infected Zimbabwean adolescents. BMC Pharmacol Toxicol. 2020 Aug 3;21(1):58. doi: 10.1186/s40360-020-00437-y. — View Citation

Vasquez E, Zegarra G, Chirinos E, Castillo JL, Taves DR, Watson GE, Dills R, Mancl LL, Milgrom P. Short term serum pharmacokinetics of diammine silver fluoride after oral application. BMC Oral Health. 2012 Dec 31;12:60. doi: 10.1186/1472-6831-12-60. — View Citation

Villa A, Anabalon M, Zohouri V, Maguire A, Franco AM, Rugg-Gunn A. Relationships between fluoride intake, urinary fluoride excretion and fluoride retention in children and adults: an analysis of available data. Caries Res. 2010;44(1):60-8. doi: 10.1159/00 — View Citation

Wilschefski SC, Baxter MR. Inductively Coupled Plasma Mass Spectrometry: Introduction to Analytical Aspects. Clin Biochem Rev. 2019 Aug;40(3):115-133. doi: 10.33176/AACB-19-00024. Review. — View Citation

World Health Organization. (2014). Basic methods for assessing renal fluoride excretion in community prevention programmes for oral health. World Health Organization. https://apps.who.int/iris/handle/10665/112662

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the silver level in the hair samples (µg/g)	SDF treatment will be provided to the patients, hair samples will be collected at day 7 after the SDF treatment	7 days
Primary	To assess the silver level in the hair samples (µg/g)	SDF treatment will be provided to the patients, hair samples will be collected at day 14 after the SDF treatment	14 days
Primary	To assess the silver level in the hair samples (µg/g)	SDF treatment will be provided to the patients, hair samples will be collected at day 30 after the SDF treatment	30 days
Primary	To assess the silver level in the hair samples (µg/g)	SDF treatment will be provided to the patients, hair samples will be collected at day 60 after the SDF treatment	60 days
Primary	To assess the silver level in the hair samples (µg/g)	SDF treatment will be provided to the patients, hair samples will be collected at day 75 after the SDF treatment	75 days
Primary	To assess the silver level in the hair samples (µg/g)	SDF treatment will be provided to the patients, hair samples will be collected at day 90 after the SDF treatment	90 days
Primary	To assess the fluoride level in the urine samples (µg/24h)	SDF treatment will be provided to the patients, urine samples will be collected before the start of the treatment; in the first and second 24 hour after the treatment	72 hours
Primary	To assess the silver level in the urine samples (µg/24h)	SDF treatment will be provided to the patients, urine samples will be collected before the start of the treatment; in the first and second 24 hour after the treatment	72 hours