A Randomized Controlled Trial of Vitamin D Supplementation on Salivary Biomarkers and Cariogenic Oral Microbiome (Incipient)

Effect of Vitamin D Supplementation on Salivary Biomarkers; Certain Proteins and Cariogenic Oral Microbiome for Medical Management of Dental Caries: A Randomized Controlled Trial

The goal of this clinical trial is to compare the treatment effect of vitamin D supplementation and topical fluorides in the population having vitamin D deficiency and Initial Carious Lesions (ICL) on the progression of ICL in teeth. This study aims to observe the changes in the International Caries Detection and Assessment System (ICDAS) scores, the concentration of salivary proteins, and cariogenic microbes, six months after the interventions.

• Group A will get vitamin D supplements and oral hygiene instructions (OHI).
• Group B will get vitamin D supplements, topical fluorides, and OHI.
• Group C (Control), the vitamin D sufficient group will get topical fluorides and OHI.

Study Overview

• Status: Recruiting
• Conditions: Dental Caries; White Spot Lesion; Initial Caries; Incipient Enamel Caries
• Intervention / Treatment: Procedure: Topical fluoride application along with behavioral modification; Dietary supplement: Vitamin D supplements along with behavioral modification; Combination product: Topical fluoride application and Vitamin D supplements along with behavioral modification

Detailed Description

The study investigator will conduct a multi-centered randomized clinical trial in the outpatient department of Operative Dentistry, in three units of Dow University of Health Sciences (DUHS), with parallel treatment assignment to an experimental, active comparator, and control groups. The investigator will recruit study participants aged 12 to 45 at moderate risk of dental caries, specifically those with vitamin D deficiency. Additionally, participants must have at least two clinically diagnosed teeth with initial carious lesions (ICL). Each participant will be enrolled for six months in this trial.

The investigator will obtain data on vitamin D deficiency from Dow Diagnostic Laboratory. Dental caries risk will be assessed using a caries risk assessment (CRA) form, while ICL will be evaluated through the International Caries Detection and Assessment System (ICDAS) scores. The investigator will collect the samples of participants' saliva to analyze salivary proteins using the enzyme-linked immunosorbent assay (ELISA), and cariogenic microbes through polymerase chain reaction (PCR).

Participants will be assigned to one of three groups randomly:

• Group A participants will be vitamin D deficient with caries, receiving vitamin D supplements and Oral hygiene instructions (OHI).
• Group B participants will be vitamin D deficient with caries, receiving vitamin D supplements, topical fluorides, and OHI.
• Group C participants will be vitamin D sufficient to be considered as controls for comparison, receiving fluoride application and OHI.

The investigator will assess study outcomes by observing changes in ICDAS scores, salivary protein concentrations, and count of cariogenic bacterial species (Streptococcal mutans and Lactobacilli).

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dr Saba Arshad; Phone Number: 02138771111; Email: saba.arshad@duhs.edu.pk
• Study Contact Backup: Name: Dr. Sadiah Muhammad Saleem Ullah Khan; Phone Number: 02199261300; Email: sadiah.saleem@uok.edu.pk

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 75330
      • Recruiting
      • Dr Saba Arshad
      • Contact: Dr Saba Arshad; Email: saba.arshad@duhs.edu.pk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients of all genders and ages ranging from 12-50 years, having at least two teeth with clinically diagnosed Initial Carious Lesions at Moderate Risk of Dental Caries, after written informed consent.
• Patients having vitamin D deficiency.

Exclusion Criteria:

• Patients who have heavy calculus, gingivitis, or periodontitis.
• Patients using desensitizing toothpaste or mouthwash up to six weeks before the study.
• Patients who have severe intestine or kidney disease, malabsorption syndrome, or any other conditions affecting vitamin D metabolism.
• Patients on antibiotics or probiotics therapy for the last month
• Pregnant females.
• Patients with poor oral hygiene and with excessive dietary exposure to acids and carbohydrates.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; vitamin D Deficient group having initial caries	Dietary supplement: Vitamin D supplements along with behavioral modification; Vitamin D soft gel capsules of 50,000 IU/week for two months followed by a maintenance dosage of 5000 IU/day for one month. Behavior modification for dental caries with standard instructions of brushing teeth twice daily with regular fluoridated toothpaste and diet counseling.
Active Comparator: Group B; vitamin D deficient group having initial caries	Combination product: Topical fluoride application and Vitamin D supplements along with behavioral modification; Professional topical 5% sodium fluoride gel application for 5 minutes on the teeth having ICL. Behavior modification for dental caries with standard instructions of brushing teeth twice daily with regular fluoridated toothpaste and diet counseling. Vitamin D soft gel capsules of 50,000 IU/week for two months followed by a maintenance dosage of 5000 IU/day for one month. Behavior modification for dental caries with standard instructions of brushing teeth twice daily with regular fluoridated toothpaste and diet counseling.
Placebo Comparator: Group C; vitamin D sufficient group having initial caries	Procedure: Topical fluoride application along with behavioral modification; Professional topical 5% sodium fluoride gel application for 5 minutes on the teeth having ICL. Behavior modification for dental caries with standard instructions of brushing teeth twice daily with regular fluoridated toothpaste and diet counseling. Behavior modification for dental caries with standard instructions of brushing teeth twice daily with regular fluoridated toothpaste and diet counseling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICDAS scores of initial caries or white spot lesions	Change in ICDAS scores of initial caries or white spot lesions	6 months
Number of growth forming units of microbial strains	Change in number of growth forming units of microbial strains	6 months
Genetic expression of target genes of S. Mutans and L. Rhamnosus	Presence or absence of genetic expression of target genes of S. Mutans and L. Rhamnosus	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Vitamin D levels	Change in Serum Vitamin D levels	6 months
Salivary protein concentration	Change in salivary protein concentration	6 months

Collaborators and Investigators

• Sponsor: Dow University of Health Sciences
• Collaborators: University of Karachi
• Investigators: Principal Investigator: Dr Saba Arshad, DUHS

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: December 12, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 8, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Dental Caries; White Spot Lesion; Initial Caries; Incipient Enamel Caries
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Diseases; Tooth Demineralization; Dental Caries; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents; Micronutrients; Protective Agents; Cariostatic Agents; Vitamin D; Ergocalciferols; Vitamins; Fluorides; Cholecalciferol; Fluorides, Topical
• Other Study ID Numbers: SArshad

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No