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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Dental Caries, White Spot Lesion, Initial Caries, Incipient Enamel Caries

Intervention / Treatment
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* Dietary Supplement: Vitamin D supplements along with behavioral modification
* Combination Product: Topical fluoride application and Vitamin D supplements along with behavioral modification
* Procedure: Topical fluoride application along with behavioral modification


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>vitamin D Deficient group having initial caries | Dietary Supplement: Vitamin D supplements along with behavioral modification<br>* 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.<br>|
| Active Comparator: Group B<br>vitamin D deficient group having initial caries | Combination Product: Topical fluoride application and Vitamin D supplements along with behavioral modification<br>* 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.<br>|
| Placebo Comparator: Group C<br>vitamin D sufficient group having initial caries | Procedure: Topical fluoride application along with behavioral modification<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dental Caries, White Spot Lesion, Initial Caries, Incipient Enamel Caries