Mouthwashes for Gingivitis: Comparing a Hydrogen Peroxide-Hyaluronic Acid Mix, Hyaluronic Acid, and Chlorhexidine, A Triple-Blind Clinical Trial

NCT07031388 | Completed

• 1 other identifier: RP-DPH-KHCMS-2025-001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, triple-blind clinical trial is designed to evaluate the efficacy of four different mouthwash formulations - hydrogen peroxide with hyaluronic acid, hyaluronic acid alone, chlorhexidine, and placebo - in four parallel arms. The study will take place at multiple centers, starting on June 1, 2025, and is expected to conclude by October 1, 2026. There is no external funding source for this study. Eligible participants include systemically healthy individuals aged 18 to 35 years with a gingival and plaque index score of 1 or higher. Individuals with systemic or oral diseases will be excluded. Participants will be randomly assigned to one of four groups, each receiving a different mouthwash formulation for twice-daily use, following standardized oral hygiene instructions. The potential benefit includes a reduced risk of gingivitis progression to periodontitis. There are no significant anticipated risks, though mild oral discomfort or taste alteration may occur.

Conditions

Plaque Induced Gingival Disease

Keywords

Triple blind clinical trial; Gingivitis; Hydrogen peroxide; Hyaluronic acid; Chlorhexidine

Outcome Measures

Primary Outcomes (3)

• Change in Gingival Index (GI) from baseline to week 3

  Mean Gingival Index score per participant, assessed on six sites per tooth. Score range: 0 (normal) to 3 (severe inflammation).

  Baseline, Week 1, Week 2, Week 3

• Change in Plaque Index (PI) from baseline to week 3

  Mean Plaque Index score per participant, assessed using the Silness and Löe method-score range: 0 (no plaque) to 3 (abundant plaque).

  Baseline, week 1, week 2, week 3

• Change in Bleeding on Probing (BOP) from baseline to week 3

  Percentage of sites showing bleeding on probing, recorded within 30 seconds after probing. Range: 0% to 100%.

  baseline, week 1, week 2, week 3

Secondary Outcomes (3)

• Change in Discomfort score after mouthwash use

  After 3 weeks of mouthwash use

• Change in taste perception after mouthwash use

  After 3 weeks of mouthwash use

• Change in tooth color shade assessed by VITA easy shade LITE

  At baseline and after 3 weeks of mouthwash use

Study Arms (4)

1- Arm 1 Hydrogen peroxide + Hyaluronic acid

EXPERIMENTAL

Participants in this arm will receive a mouthwash formulation containing 1.8% hydrogen peroxide and 0.10% hyaluronic acid. The mouthwash is to be used twice daily for 3 weeks, following standardized oral hygiene instructions. This combination is intended to synergize the antimicrobial effects of hydrogen peroxide with the anti-inflammatory and healing properties of hyaluronic acid to manage gingivitis.

Combination Product: 1-Hydrogen peroxide and hyaluronic acid

2- Arm 2 Hyaluronic acid alone

EXPERIMENTAL

Participants in this arm will use a mouthwash containing 0.12% high molecular weight hyaluronic acid only. The mouthwash will be used twice daily for 3 weeks. Hyaluronic acid is known for its anti-inflammatory, tissue repair, and moisturizing effects, and this arm will assess its standalone effectiveness in improving gingival health in patients with gingivitis.

Combination Product: 2- Hyaluronic acid

3- Arm 3 chlorhexidine (CHX)

EXPERIMENTAL

Participants in this arm will receive a commercially available mouthwash containing 0.12% chlorhexidine gluconate. The solution will be used twice daily for 3 weeks, following standardized oral hygiene instructions. Chlorhexidine is a widely used antiseptic known for its broad-spectrum antimicrobial activity and effectiveness in reducing plaque and gingival inflammation.

Combination Product: Chlorhexidine

4- Arm 4 placebo

PLACEBO COMPARATOR

Participants in this arm will receive a placebo mouthwash designed to closely mimic the active treatments in appearance, taste, and viscosity, ensuring effective blinding. The formulation comprises: * 2 ml glycerin * Vanilla flavoring agent * Brown food coloring * Distilled water to make up 1 liter This placebo was prepared at Awamedica, a certified Class A pharmaceutical manufacturer known for its state-of-the-art formulation laboratory and commitment to quality in pharmaceutical manufacturing. The solution is dispensed in 120 ml opaque brown bottles, each labeled solely with the participant's number to maintain blinding. Participants are instructed to use the mouthwash twice daily for 3 weeks, following standardized oral hygiene instructions. This arm serves as a negative control to assess the true efficacy of the active mouthwash formulations in managing gingivitis.

Combination Product: Placebo mouthwash

Interventions

1-Hydrogen peroxide and hyaluronic acid COMBINATION_PRODUCT

Hydrogen Peroxide (1.80%): Acts as an antiseptic agent, releasing oxygen that helps in reducing bacterial load and disrupting biofilms associated with gingivitis. * Hyaluronic Acid (0.10%): A naturally occurring polysaccharide known for its anti-inflammatory and tissue-regenerative properties, aiding in the healing of gingival tissues Clinical studies have demonstrated the efficacy of Perhyal in managing gingivitis. In a randomized controlled trial, Perhyal showed a significant reduction in gingival inflammation compared to placebo, with no reported adverse effects over 21 days.

1- Arm 1 Hydrogen peroxide + Hyaluronic acid

2- Hyaluronic acid COMBINATION_PRODUCT

This intervention involves the use of a mouthwash containing hyaluronic acid (0.12%) of high molecular weight, without any additional active agents. Hyaluronic acid is a naturally occurring substance known for its anti-inflammatory and wound-healing properties. It supports gingival tissue regeneration and hydration, which may contribute to reducing signs of gingivitis such as redness, swelling, and bleeding. Participants assigned to this arm will rinse with 10 mL of the solution twice daily for three weeks, following standardized oral hygiene instructions. This arm serves to evaluate the independent therapeutic effect of hyaluronic acid in managing gingival inflammation.

2- Arm 2 Hyaluronic acid alone

Chlorhexidine COMBINATION_PRODUCT

This intervention uses a commercially available chlorhexidine gluconate 0.12% mouthwash, widely recognized for its strong antimicrobial properties. Chlorhexidine is considered a gold-standard agent for chemical plaque control and is effective in reducing bacterial load, gingival inflammation, and bleeding. Participants in this group will rinse with 10 mL of the solution twice daily for three weeks, in addition to maintaining regular oral hygiene practices.

3- Arm 3 chlorhexidine (CHX)

Placebo mouthwash COMBINATION_PRODUCT

This placebo mouthwash was specially formulated to visually and sensorially resemble the active mouthwash products without containing any active therapeutic ingredients. It was prepared in the AwaMedica laboratory using 1 liter of distilled water, 98.5% distilled water, 2 mL of glycerin for mild viscosity, 5 mL of vanilla flavoring for taste masking, and 8 mL of brown food coloring to match the appearance of chlorhexidine. The solution was stored in 120 mL opaque brown bottles, each labeled only with the participant number to ensure blinding. Participants will use 10 mL of the placebo rinse twice daily for three weeks, following the same oral hygiene protocol as other groups.

4- Arm 4 placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects with a gingival index score of 1 or greater.
• Subjects with a plaque index score of 1 or greater
• Systemically healthy individuals.
• Minimum of 20 natural teeth

You may not qualify if:

• Current use of any mouthwash.
• Smoking habit.
• Presence of active caries.
• Overhanged restorations and crowns.
• Presence of supra or subgingival calculus.
• Ongoing orthodontic treatment (including post-treatment retainer)
• Periodontal treatment within the past 6 months and a diagnosis of periodontitis.
• Use of antibiotics within the past 4 months or requirement for antibiotic prophylaxis.
• Systematic or topical non-steroidal anti-inflammatory drug treatment for the past 4 months
• Pregnancy or lactation.
• History of heart valve replacement.
• Known intolerance or allergy to mouth rinses.

Sponsors & Collaborators

• Ramziyah Hayder Bakr: lead

Study Sites (1)

khanzad specialized health centre + Hwler dental center + Azadi dental center + Students of Hawler medical college

Erbil, Kurdistan, 00441, Iraq

Location

MeSH Terms

Conditions

Gingivitis

Interventions

Hyaluronic Acid; Chlorhexidine

Condition Hierarchy (Ancestors)

Infections; Gingival Diseases; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Board Candidate in Dental Public Health

Model Details: Participants are randomly assigned to one of four parallel treatment groups, each receiving a different mouthwash intervention for gingivitis management.

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: June 22, 2025
• Study Start: July 1, 2025
• Primary Completion: September 1, 2025
• Study Completion: October 17, 2025
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

IR (1)