Evaluation of the Anti-septic Effect of a Chlorhexidine (CHX) Mouthwash With or Without an Anti-Discoloration System (ADS) During Experimental Gingivitis

Protocol Title Evaluation of the Anti-septic Effect of a Chlorhexidine (CHX) Mouthwash With or Without an Anti-Discoloration System (ADS) Compared to Placebo, During Experimental Gingivitis

Recently, a chlorhexidine product with an anti-discoloration system (ADS) was launched in the market. A comparative study was done to confirm the effectiveness of 0.2% chlorhexidine with ADS. The study was single-blinded. In the experimental period, volunteers maintained their usual oral hygiene habits, besides, they rinsed twice daily with mouthwash (0.2% chlorhexidine) with or without ADS. Obviously, subject's home oral hygiene may become a major confounder of plaque accumulation. Although the effect of ADS is statistically significant, the ability of this new product to prevent plaque accumulation and gingivitis remained highly questionable.

Hence, controversy exists about the clinical efficacy of the chlorhexidine products with ADS. Consequently, a clinical validation of such products appears necessary. In the present study, the 21-day experimental gingivitis model will be used. This model is an established non-invasive model in humans for investigating the induction and resolution of inflammation in response to increasing bacterial accumulation. The design enables a study to be performed over 35 days in a well-controlled manner. So far, it is the most accurate clinical study model to access how medication or compounds in dentifrices affect plaque accumulation and gingival inflammation.

Study Overview

• Status: Enrolling by invitation
• Conditions: Gingivitis Infection
• Intervention / Treatment: Other: Experimental gingivitis model

Detailed Description

Chlorhexidine is the most effective anti-plaque agent to date. It was more widely used in medicine and surgery. Löe and Schiött (1970) firstly studied its application in dentistry. The study showed that rinsing for 60 seconds twice per day with 10ml of a 0.2% chlorhexidine gluconate solution in the absence of normal tooth cleaning, inhibited plaque regrowth and the development of gingivitis. Because chlorhexidine is a bis-biguanide with a strong base and cationic, it reacts with anions, which is related to its antimicrobial activity. It has no systemic toxicity from topical application or ingestion. However, two pronounced side effects - superficial staining of the teeth and altered taste perception - were recognized almost immediately. This may compromise patient compliance for esthetic reasons. Recently, a chlorhexidine product with an anti-discoloration system (ADS) was launched in the market. A comparative study was done to confirm the effectiveness of 0.2% chlorhexidine with ADS. The study was single-blinded. In the experimental period, volunteers maintained their usual oral hygiene habits, besides, they rinsed twice daily with mouthwash (0.2% chlorhexidine) with or without ADS. Obviously, subject's home oral hygiene may become a major confounder of plaque accumulation. Although the effect of ADS is statistically significant, the ability of this new product to prevent plaque accumulation and gingivitis remained highly questionable.

Hence, controversy exists about the clinical efficacy of the chlorhexidine products with ADS. Consequently, a clinical validation of such products appears necessary. In the present study, the 21-day experimental gingivitis model will be used. This model is an established non-invasive model in humans for investigating the induction and resolution of inflammation in response to increasing bacterial accumulation. The design enables a study to be performed over 35 days in a well-controlled manner. So far, it is the most accurate clinical study model to access how medication or compounds in dentifrices affect plaque accumulation and gingival inflammation.

Chlorhexidine is the most effective anti-plaque agent to date. It was more widely used in medicine and surgery. Löe and Schiött (1970) firstly studied its application in dentistry. The study showed that rinsing for 60 seconds twice per day with 10ml of a 0.2% chlorhexidine gluconate solution in the absence of normal tooth cleaning, inhibited plaque regrowth and the development of gingivitis. Because chlorhexidine is a bis-biguanide with a strong base and cationic, it reacts with anions, which is related to its antimicrobial activity. It has no systemic toxicity from topical application or ingestion. However, two pronounced side effects - superficial staining of the teeth and altered taste perception - were recognized almost immediately. This may compromise patient compliance for esthetic reasons. Recently, a chlorhexidine product with an anti-discoloration system (ADS) was launched in the market. A comparative study was done to confirm the effectiveness of 0.2% chlorhexidine with ADS. The study was single-blinded. In the experimental period, volunteers maintained their usual oral hygiene habits, besides, they rinsed twice daily with mouthwash (0.2% chlorhexidine) with or without ADS. Obviously, subject's home oral hygiene may become a major confounder of plaque accumulation. Although the effect of ADS is statistically significant, the ability of this new product to prevent plaque accumulation and gingivitis remained highly questionable.

Hence, controversy exists about the clinical efficacy of the chlorhexidine products with ADS. Consequently, a clinical validation of such products appears necessary. In the present study, the 21-day experimental gingivitis model will be used. This model is an established non-invasive model in humans for investigating the induction and resolution of inflammation in response to increasing bacterial accumulation.

During the study period, participants will be asked to rinse with the mouthrinse sample or the placebo for 60 seconds twice daily, under video supervision (participants send in video recordings of their rinsing to control adherence to the protocol). A dental assistant, unaware of the study's purpose, will distribute the samples. The containers will be unlabeled, ensuring that both the participants and examiners are blinded to group allocation.

At Days 0, 7, 14 and 21 of the experiment, clinical examinations will be performed from central incisors to the second molars in each participant. The Discoloration Index (DI17) will be recorded at three aspects on each tooth (mesial, buccal and distal). The criteria for the Discoloration Index (DI) are indicated in Table 1. Plaque and Gingivitis Indices will be assessed at 4 aspects of each tooth (mesial, buccal, distal and lingual) using the criteria of the Plaque Index system (PlI) (Silness & Löe 1964) and the Gingival Index System (GI) (Löe & Silness 1963) 16, 18. At each visit, the parameters will be assessed by the same examiner, who will be masked by the allocation of the test and control to avoid examiner bias and calibration bias.

Upon completion of the experimental period, mechanical daily plaque control measures will be re-instated and the participants will be re-examined after 3 weeks to ensure their periodontal health. Following the experimental period, another professional cleansing will be performed to remove plaque and possible stain on the teeth. At day 35 the participants will be checked again.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3010
      • Department of Periodontology, University of Bern

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• systemically healthy,
• non-smoker, former smokers > 5 years,
• at least 24 teeth,
• clinical diagnosis of periodontal health or gingivitis as determined by pocket probing depth not exceeding 4 mm with concomitant bleeding on probing.

Exclusion Criteria:

• clinically visible carious lesions,
• systemic antibiotics within 3 months prior to enrolment
• vulnerable persons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group; Group P rinses twice daily with 10 ml of a placebo (pure water with flavored additive) solution	Other: Experimental gingivitis model; After a preparatory phase of prophylaxis and 3 weeks of optimal oral hygiene practice, the plaque and gingivitis scores of the participants will approach zero. The participants will then be asked to abolish all measures for mechanical plaque control for a period of 3 weeks according to the experimental gingivitis model.
Experimental: Group T1; Group T1 rinses twice daily with 10 ml of 0.12% chlorhexidine solution with ADS (Anti-Discoloration System) solution (Curasept ADS 212)	Other: Experimental gingivitis model; After a preparatory phase of prophylaxis and 3 weeks of optimal oral hygiene practice, the plaque and gingivitis scores of the participants will approach zero. The participants will then be asked to abolish all measures for mechanical plaque control for a period of 3 weeks according to the experimental gingivitis model.
Experimental: Group T2; Group T2 rinses twice daily with 10 ml of 0.12% chlorhexidine with HA (Hyaluronic Acid)	Other: Experimental gingivitis model; After a preparatory phase of prophylaxis and 3 weeks of optimal oral hygiene practice, the plaque and gingivitis scores of the participants will approach zero. The participants will then be asked to abolish all measures for mechanical plaque control for a period of 3 weeks according to the experimental gingivitis model.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of gingival inflammation, assessed by the Gingival Index by Löe and Silness 1963	The index is a scoring system 0, 1, 2, or 3 where 0 is defining normal gingiva to 3 representing severe inflammation with spontaneous bleeding	at day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of gingival inflammation, assessed by the Gingival Index by Löe and Silness 1963	The index is a scoring system 0, 1, 2, or 3 where 0 is defining normal gingiva to 3 representing severe inflammation with spontaneous bleeding	at day 0, 7, 14, and 35
Plaque accumulation, assessed by the Plaque Index Silness and Löe 1994	The index is a scoring system assessing the plaque at 4 surfaces of the teeth, starting at 0 for no plaque visible to 3 with an abundance of plaque creating a thick layer that fills the interdental space.	at day 0, 7, 14, 21 and 35
Staining assessed by the Discoloration index	The discoloration is an index from 0: no discoloration to 3: Heavy brown and black discoloration over the entire extent of the tooth surface, black discoloration predominantly on the interproximal surfaces	at day 0, 7, 14, 21 and 35
Oral scan	Oral scans will be performed to study changes in gingival texture, volume and colour or other changes	at day 0, 21 and 35
Microbiological changes	Changes in 8 periodontopathogens will be assessed by Multiplex PCR	at day 0, 21 and 35
Characterisation of host- and microbiome-derived metabolites	From selective participants, host-derived metabolites will be assessed by untargeted liquid chromatography-mass spectrometry (LC-MS) to study molecular changes throughout disease progression and possible relationships with other generated datasets.	at day 0, 21 and 35

Collaborators and Investigators

• Sponsor: University of Bern

Study record dates

Study Major Dates

• Study Start (Estimated): July 8, 2026
• Primary Completion (Estimated): September 7, 2026
• Study Completion (Estimated): August 7, 2027

Study Registration Dates

• First Submitted: July 6, 2026
• First Submitted That Met QC Criteria: July 6, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: experimental gingivitis; gingivitis model; mouth-rinses with anti-discoloration system
• Other Study ID Numbers: V4ExpAugGingivitis

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