Comprehensive Multi-omics Characterization and Implications of Non-Pharmaceutical Dental Hygiene Product in a Randomized Controlled Large Population Study.

NCT07451782 | Completed

• 1 other identifier: DDMNF 24-001/ D-0205-2024
• Study Type: interventional
• Target: 595
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of this clinical study are:

1. 1.Survey approximately 600 persons between the ages of 18-80 regarding their medical history \& oral hygiene habits, diet \& exercise habits, and emotional \& physical stressors to understand the barriers this population may face in achieving or maintaining good oral care and whole body health.
2. 2.Compare the survey results with the organic molecule data collected by oral swabs from each subject at three different time points over the course of their 60 day study participation to better understand how behaviors and medical history relate to oral and whole body health.
3. 3.Assess the effectiveness of two marketed oral hygiene study products vs a control on oral microbiome--such as bacteria, fungi, viruses that live naturally in our body-as well as its impact on the oral microbiome of each subject.

Conditions

Basic Science; Intervention Studies; Biomarker Discovery

Keywords

Oral Microbiome; Dental Hygiene; Risk Factors; Intervention

Outcome Measures

Primary Outcomes (5)

• Metagenomic changes at 4 and 8 weeks from baseline in pHossident lozenge recipients vs Protektin water additive recipients vs control participants using shotgun sequencing of salivary DNA isolates sequencing depth of 35.4M read pairs per sample.

  Shotgun sequencing (Illumina NovaSeq X, 2x150bp) of salivary DNA isolates using a sequencing depth of 35.4M read pairs per sample. Data processing through Cmbio Human Microbiome Profiler for taxonomic and functional profiling. Significance determination using the Student's t-test and FDR values for differential abundance across cohorts and over time. Changes in microbial metagenome with focus on the levels of specific commensal species and pathogen species are measured by copy number of specific genomic sequences in a sample relative to the total. High resolution taxonomic profiling will be used to identify species and strains and their relative abundance in a patient sample and how that abundance changes over time and between treatment groups for each microbial species. Anticipate decreases in pathogen species in treatment groups vs control. Units of measurement = # of genome copies and % abundance in the sample.

  Initial visit: baseline measurements to 8 week endpoint measurements

• Metabolomic changes at 4 and 8 weeks from baseline in pHossident lozenge vs Protektin water additive recipients vs control using metabolite profiling of oral swab samples with UHPLC-Orbitrap MS.

  Changes in oral metabolome, ie, the levels of specific metabolites that are measured by peak analyses derived from retention time and fragmentation compared to reference standards obtained from samples and measured using ultra-high pressure liquid chromatography-Orbitrap Mass Spectrometry. High resolution data are normalized for biological and sample variation and processed using Systematic Error Removal using Random Forest (SERRF). Probabalistic quotient normalization will be used to address dilution effects and concentration variability in the metabolomics dataset. Principal component analysis will be used to examine statistical patterns of metabolites within a group and across groups. Score plots will be used to show clustering of patient samples that are similar for each metabolite. Units of measurement = untransformed probailistic quotient normalized (PQN) peak areas of each metabolite, and power-transformed PQN peak areas.

  Baseline time point to week 8 endpoint.

• Inflammation-related Analysis

  Inflammation-related protein biomarker (IL-6, MMP-8, MMP-13) levels and their changes at 4 and 8 weeks from baseline in pHossident lozenge vs Protektin water additive recipients vs control is examined. Oral swab samples are collected and biomarkers are measured using standard curves of recombinant protein biomarker in the enzyme-linked immunosorbent assays (ELISA) specific to each protein biomarker. Significance is determined using the Student's t-test in each cohort over time and across cohorts at each time point. Units of measurement = micrograms/mL levels of each protein biomarker in a sample.

  Baseline time point to endpoint 8 week time point.

• Inter-omics correlations

  The purpose of this analysis is to answer the question: Does the intervention (lozenge or water additive) have a common co-varying effect across the metagenome, metabolome and/or the immunological marker(s)? Additionally, to identify statistically significant correlational relationships between species withing the metagenome, metabolites and inflammation biomarkers. Analyses will be conducted with regards to change from baseline in response to the intervention and compared to the control cohort. Additional analyses will be conducted to examine the differences in the metagenome, metabolome and/or immune markers between pHossident vs Protektin treatment groups. Machine learning prediction models will be used to assess association between datasets. False discovery rate (FDR) and P-values will be assessed using the Benjamini-Hochberg method. All statistical analyses will be performed in R version 4.4.2. Units of measurement = Relative abundance, unit variance, intensity in heat maps.

  Baseline to 8 week endpoint.

• Exploratory baseline analyses

  * Observational inspection of the oral metagenome and metabolome in the study population. * Analysis of the questionnaire data with respect to general physical health, dental hygiene, diet, mental health and exercise habits in the study population. * Analysis of the inflammation protein biomarkers MMP-8, MMP-13 and IL-6 levels in the study population. * Correlation analyses, cluster analysis, of the relationship in these meta-data and multi-omic data using machine learning to assess R-squared to test ordinal variables. Statistical analysis using R. Units of measurements = intensity, relative abundance, unit score will be presented in heat maps to show strength and type of correlation.

  Baseline

Study Arms (3)

Lozenge Intervention (Tradename pHossident)

ACTIVE COMPARATOR

This cohort was randomized and assigned into the pHossident Lozenge cohort. They received 8 lozenges per day for the duration of the study. They completes questionnaires. They were sampled orally at Baseline, Week 4 and Week 8 for multi-omic analyses.

Dietary Supplement: Oral Lozenges (Tradename pHossident)

Control

NO INTERVENTION

Full participation but received no intervention

Water Additive Intervention (Tradename Protektin)

ACTIVE COMPARATOR

This cohort was randomized and assigned into the Protektin water additive cohort. They received 2 water additive sachets per day for the duration of the study. They completes questionnaires. They were sampled orally at Baseline, Week 4 and Week 8 for multi-omic analyses.

Dietary Supplement: Water additive (Tradename Protektin)

Interventions

Oral Lozenges (Tradename pHossident) DIETARY_SUPPLEMENT

dissolvable mint flavored pHossident lozenges containing ingredients that are all FDA-approved with the GRAS (Generally Recognized As Safe) designation, and have years of safety demonstrated in animals, children, adults and pregnant women. The lozenge is not classified as a drug and is regulated as a nutritional supplement. The lozenge does contain the sugar substitutes called mannitol and sorbitol (sugar alcohols), as well as the natural sweetener, stevia, all of which can irritate the lower gastrointestinal tract at amounts that grossly exceed the levels that are contained in the lozenges (I lozenge contains \<l % of the recommended daily intake).

Lozenge Intervention (Tradename pHossident)

Water additive (Tradename Protektin) DIETARY_SUPPLEMENT

Commercially marketed over-the-counter Protektin drinking water additive contains ingredients that are all FDA-approved with the GRAS designation, and have years of safety demonstrated in animals, children, adults and pregnant women. The water additive is not classified as a drug and is regulated as a nutritional supplement. The water additive only contains active ingredients; it does not contain fillers, flavors or sweeteners.

Water Additive Intervention (Tradename Protektin)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (18 to 80 years old), all genders, all incomes, of any race (target of 20% non- Caucasian;
• Non-smokers or those who have currently stopped for at least 2 years;
• Can wear full dentures;
• No oral antibiotic taken in the past 30 days;
• May have gums that sometimes bleed upon brushing, flossing or eating;
• Willing to take an investigational dental hygiene product, daily, for 60 days;
• Must be able to read and understand the consent;
• Must be willing to answer study questionnaires at the clinical site using a laptop;
• Must be willing to participate in 3 onsite clinical visits.

You may not qualify if:

• Subject is pregnant or breastfeeding
• Subject has been on an oral antibiotic within the previous 30 days;
• Subject participated in a dental plaque/gingivitis/periodontal clinical trial within the previous 30 days;
• If the subject reports an allergy to any of the ingredients listed in the ingredient safety information provided in the Appendix.

Sponsors & Collaborators

• Delta Dental of Minnesota Foundation: lead
• Comprehensive Research Group: collaborator
• Primal Therapies Inc.: collaborator
• Clinical Microbiomics: collaborator

Study Sites (1)

Comprehensive Research Group

Minneapolis, Minnesota, 55415, United States

Location

Study Officials

• Bruce Templeton, DMD

  Delta Dental of Minnesota Foundation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Outcome Assessor blinded until completion of primary data analysis and unblinded for secondary data analysis.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Group 1: an oral lozenge supplement an oral lozenge supplement, Group 2: a water additive supplement Group 3: a control group without an assigned supplement

Study Record Dates

• First Submitted: December 22, 2025
• First Posted: March 5, 2026
• Study Start: April 30, 2024
• Primary Completion: July 11, 2024
• Study Completion: July 23, 2025
• Last Updated: March 5, 2026

Record last verified: 2026-02

Locations

US (1)