Adjunctive Topical Melatonin Gel in Non-Surgical Periodontal Therapy for Periodontitis

Evaluation of Clinical Outcomes of Adjunctive Topical Melatonin Gel in Non-Surgical Periodontal Therapy: A Randomized Placebo-Controlled Trial in Karachi

The goal of this clinical trial is to evaluate the clinical effectiveness of adjunctive topical melatonin gel when used with non-surgical periodontal therapy (NSPT) in adult patients with periodontitis. This study includes systemically healthy or medically controlled patients aged 18-45 years who are diagnosed with periodontitis and attend the Department of Periodontology at Liaquat College of Medicine & Dentistry, Karachi.

The main questions it aims to answer are:

• Does adjunctive topical 5% melatonin gel improve clinical attachment level (CAL) compared to placebo after NSPT?
• Does adjunctive topical 5% melatonin gel improve plaque index (PI), gingival index (GI), and periodontal pocket depth (PPD) compared to placebo after NSPT? Researchers will compare patients receiving NSPT with topical melatonin gel to patients receiving NSPT with placebo gel to determine whether melatonin provides additional clinical benefits in periodontal therapy.

Participants will:

• Undergo baseline periodontal examination, including assessment of plaque index, gingival index, periodontal pocket depth, and clinical attachment level.
• Receive non-surgical periodontal therapy (scaling and root planing).
• Be randomly assigned to receive either 5% topical melatonin gel or placebo gel applied intra-pocket.
• Attend follow-up visits for gel application and monitoring.
• Undergo reassessment of clinical periodontal parameters after three months.
• Be monitored for any adverse effects during the study period. This study is a randomized, double-blind, placebo-controlled clinical trial evaluating the role of topical melatonin gel as an adjunct to conventional non-surgical periodontal therapy in improving periodontal clinical outcomes.

Study Overview

• Status: Completed
• Conditions: Periodontal Disease; Melatonin
• Intervention / Treatment: Drug: Topical 5% Melatonin Gel; Other: Placebo

Detailed Description

Periodontitis is a chronic inflammatory disease affecting the supporting structures of the teeth and is one of the leading causes of tooth loss worldwide. The disease is initiated by pathogenic bacterial biofilm and progresses through a complex host inflammatory response that results in destruction of the periodontal ligament, alveolar bone loss, periodontal pocket formation, and clinical attachment loss. In Pakistan, periodontitis has a high prevalence and represents a significant oral health burden affecting quality of life and overall health.

Non-surgical periodontal therapy (NSPT), consisting primarily of scaling and root planing, is considered the gold standard treatment for periodontitis. NSPT effectively reduces microbial load and improves periodontal clinical parameters, including plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL). However, despite the effectiveness of mechanical debridement, complete resolution of inflammation and periodontal tissue regeneration may not always be achieved, leading researchers to investigate adjunctive therapeutic approaches.

Melatonin is a naturally occurring hormone mainly secreted by the pineal gland and is known for regulating circadian rhythm. In addition to its physiologic role, melatonin possesses antioxidant, anti-inflammatory, immunomodulatory, and bone-regenerative properties. Experimental and clinical studies have suggested that melatonin may reduce oxidative stress, regulate inflammatory mediators, inhibit tissue destruction, and promote osteoblastic activity and collagen formation. These biologic effects indicate its potential usefulness as an adjunctive agent in periodontal therapy.

Previous international studies have demonstrated promising results with topical melatonin application in periodontal treatment, showing improvements in inflammatory parameters and periodontal healing. However, there is limited evidence regarding its clinical effectiveness in the Pakistani population, and no randomized placebo-controlled clinical trial has been conducted locally to evaluate its adjunctive role with NSPT.

This study is designed as a randomized, double-blind, placebo-controlled clinical trial to assess the clinical outcomes of adjunctive topical melatonin gel in patients undergoing non-surgical periodontal therapy. A total of 30 patients diagnosed with periodontitis will be recruited from the Department of Periodontology at Liaquat College of Medicine & Dentistry, Karachi. Eligible participants will include adults aged 18-45 years who are systemically healthy or medically controlled and diagnosed with periodontitis with clinical attachment loss between 3-4 mm.

Participants will be randomly allocated into two groups. The experimental group will receive NSPT followed by intra-pocket application of 5% topical melatonin gel, while the control group will receive NSPT followed by placebo gel application. Both gels will be similar in appearance to maintain blinding. The study will follow a double-blind design in which both participants and the primary investigator assessing outcomes will remain unaware of group allocation.

Clinical periodontal parameters, including Plaque Index (PI), Gingival Index (GI), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL), will be recorded at baseline and reassessed after three months. Participants will also be monitored for adverse effects such as burning sensation, taste alteration, or mucosal irritation throughout the study period.

The primary objective of the study is to compare the clinical effectiveness of adjunctive topical melatonin gel with placebo in improving periodontal clinical outcomes following NSPT. The findings of this study may contribute to the growing evidence regarding host-modulatory therapy in periodontics and help determine whether topical melatonin can serve as a cost-effective adjunctive treatment option in periodontal care within the local population.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 7290
      • Liaquat College of Medicine and Dentistry

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged 18-45 years
• Patients diagnosed with periodontitis with clinical attachment loss (CAL) between 3-4 mm
• Systemically healthy individuals
• Patients with controlled systemic diseases (ASA I & II)
• Patients willing to participate and provide informed consent

Exclusion Criteria:

• Smokers or tobacco users
• Pregnant or lactating females
• Patients with uncontrolled diabetes mellitus (HbA1c >6.5%)
• Patients who received periodontal therapy within the last 6 months
• Patients who used antibiotics, anti-inflammatory drugs, sleeping pills, or antioxidant supplements within the last 6 months
• Individuals working night shifts -Patients with mental illness or neuromuscular disorders-
• Patients unwilling to participate or unable to comply with follow-up visits

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Group; Participants in the experimental group received non-surgical periodontal therapy (scaling and root planing) followed by intrapocket application of 5% topical melatonin gel. The gel was applied weekly during the first month after therapy. Clinical periodontal parameters, including Plaque Index (PI), Gingival Index (GI), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL), were evaluated at baseline and after three months to assess treatment outcomes.	Drug: Topical 5% Melatonin Gel; A locally delivered 5% topical melatonin gel applied intra-pocket as an adjunct to non-surgical periodontal therapy (scaling and root planing). The gel was prepared using a standardized gel base and administered weekly during the first month of treatment. Melatonin gel was used to evaluate its potential anti-inflammatory, antioxidant, and periodontal healing effects in patients with periodontitis.
Placebo Comparator: Control Group; Participants in the control group received non-surgical periodontal therapy (scaling and root planing) followed by intrapocket application of placebo gel identical in appearance to the melatonin gel but without the active ingredient. The placebo gel was applied weekly during the first month after therapy. Clinical periodontal parameters, including Plaque Index (PI), Gingival Index (GI), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL), were evaluated at baseline and after three months to assess treatment outcomes.	Other: Placebo; A locally delivered placebo gel applied intrapocketly as an adjunct to non-surgical periodontal therapy (scaling and root planing). The placebo gel contained the same gel base and appearance as the experimental melatonin gel but without the active melatonin ingredient. It was administered weekly during the first month of treatment to serve as a control for comparison of clinical periodontal outcomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Probing Pocket Depth (PPD)	Measured using a UNC-15 periodontal probe in millimeters from baseline to 3 months following non-surgical periodontal therapy.	3 Months
Change in Clinical Attachment Level (CAL)	Measured using a UNC-15 periodontal probe in millimeters from baseline to 3 months following non-surgical periodontal therapy.	3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gingival Index (GI)	Assessed using standardized gingival inflammation scoring from baseline to 3 months following therapy.	3 Months
Change in Plaque Index (PI)	Assessed using standardized plaque accumulation scoring from baseline to 3 months following therapy.	3 Months

Collaborators and Investigators

• Sponsor: Liaquat College of Medicine and Dentistry

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2025
• Primary Completion (Actual): January 5, 2026
• Study Completion (Actual): April 10, 2026

Study Registration Dates

• First Submitted: April 29, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 26, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Periodontal Diseases
• Other Study ID Numbers: ASRB/No./09930/MS

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