Effect of Enzyme-containing Lozenge on Dental Biofilm Formation, Composition and Functionality

The Effect of Non-biocidal Adjuncts on the Formation, Composition, Functionality, and Microscale Architecture of Dental Biofilms: a Randomized Controlled Trial

A double-blind, placebo-controlled randomized cross-over trial evaluating the effect of enzyme-containing lozenge on in vivo and in situ grown dental biofilm accumulation. The study includes two phases, one each for the investigation of in-vivo and in-situ grown dental biofilm

Study Overview

• Status: Recruiting
• Conditions: Dental Biofilm Accumulation
• Intervention / Treatment: Dietary supplement: Enzyme containing lozenge

Detailed Description

Up to 50 subjects (aged ≥ 18 years old) with 3 or more active caries lesion, will be randomized to receive:

Phase 1: The effect of multiple-enzyme treatment on plaque accumulation in vivo

Phase 1 includes two experimental periods lasting for one day each, with a washout period of two weeks in between. Each experimental period will include two visits, at day 0 and day 1.

At day 0, the participants will receive a professional tooth cleaning and be randomized to receive Sequence 1 or Sequence 2 in a double-blind randomized cross-over design:

Sequence 1: 3 active enzyme-containing lozenges per day for one day (app. 24h) followed by a washout period of two weeks, followed by 3 identical placebo lozenges per day for one day (app. 24h).

Sequence 2: 3 placebo lozenges per day for one day (app. 24h) followed by a washout period of two weeks, followed by 3 identical active enzyme lozenges per day for one day (app. 24h).

The participants will be instructed to take one lozenge three times (morning, noon, evening) for one day. No normal oral hygiene procedures will be allowed during the intervention periods of one day. At the end of both experimental phases, plaque is assessed using planimetric recordings obtained with an intraoral camera and TM-QHPI to provide information on the individual level of plaque formation.

Phase 2: The effect of multiple-enzyme treatment on in situ-grown biofilms

The phase is designed in a double-blind randomized cross-over design, including two experimental periods lasting for 2 days, with a washout period of 5 days in between. Each experimental period will include two visits, on day 0 and day 2. Oral biofilms will be grown in situ on prefabricated non-fluorescent glass slabs for 48 hours. The glass slabs will be mounted on the individual lower-jaw splints.

At day 0, the participants will be randomized to receive Sequence 1 or Sequence 2:

Sequence 1: 3 active enzyme-containing lozenges per day for 2 days followed by a washout period of 5 days, followed by 3 identical placebo lozenges per day for 2 days.

Sequence 2: 3 placebo lozenges per day for 2 days followed by a washout period of 5 days, followed by 3 identical active enzyme lozenges per day for 2 days.

Oral biofilms will be grown in situ on prefabricated non-fluorescent glass slabs for 2-4 experimental periods of 48 hours. After each experimental period, the in situ-grown biofilms will be collected and stored in a research biobank.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caterina Holz, PhD; Phone Number: +4930921076550; Email: caho@novozymes.com
• Study Contact Backup: Name: Inge Knap; Email: inkn@novozymes.com

Study Locations

• Denmark
  • Aarhus, Denmark, DK-8000 Aarhus C
    • Recruiting
    • Department of Dentistry and Oral Health, Aarhus University
    • Contact: Sebastian Schlafer, PhD; Phone Number: (+45) 4297 6020; Email: sebastians@dent.au.dk
    • Contact: Pernille Rikvold; Email: ptr@dent.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males and females ≥ 18 years old.
• Have three or more active carious lesions.
• Anatomically possible to manufacture an intraoral lower-jaw splint.
• Able to understand and follow instructions, as well as to read and sign the informed consent form.
• A plaque index score ≥ 2 according to the Turesky Modification of the Quigley-Hein Plaque Index (TM-QHPI), following 8 to 12 hours plaque accumulation period.

Exclusion Criteria:

• History of allergies towards any of the ingredients in the test products
• Self-reported pregnant or nursing
• Antibiotic or anti-inflammatory medication within 90 days of the screening visit.
• Orthodontic appliances, including retainers, or removable partial dentures.
• Self-reported serious medical conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active arm; Enzyme-containing lozenge	Dietary supplement: Enzyme containing lozenge; Lozenge containing multiple enzyme combination
Placebo Comparator: Placebo arm; Placebo lozenge	Dietary supplement: Enzyme containing lozenge; Lozenge containing multiple enzyme combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in in-vivo dental biofilm accumulation	To investigate the effect of an enzyme-containing lozenge on dental biofilm accumulation in caries-active subjects in vivo assessed by the planimetric plaque index (PPI)	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in in-vivo dental biofilm accumulation	To investigate the effect of an enzyme-containing lozenge on dental biofilm accumulation in caries-active subjects in vivo assessed by the Turesky-modified Quigley Hein Plaque Index (TM-QHPI)	1 days
Change in in-situ grown dental biofilm accumulation	The effect of enzyme-containing lozenge on changes in the microarchitecture of in situ-grown biofilms from caries-active subjects analyzed by optical coherence tomography.	2 days
Change in oral microbial community composition of in-situ grown dental biofilm	Shift in oral microbial community composition of in situ-grown biofilms from caries-active subjects assessed by next-generation sequencing of 16S rRNA genes	2 days

Collaborators and Investigators

• Sponsor: Novozymes A/S
• Collaborators: University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2023
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Actual): November 21, 2023

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Diseases; Dental Deposits; Dental Plaque
• Other Study ID Numbers: NZ-2022-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No