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CompletedNCT07565181ZO-RASUpdated May 4, 2026

Effect of Zinc Oxide Ointment on Recurrent Aphthous Stomatitis

A Phase 4 interventional study of zinc oxide and Placabo in Recurrent Aphthous Stomatitis, sponsored by Faculty of Dental Medicine for Girls. Completed at 1 site in Egypt. Open to participants aged 16 Years to 45 Years. Per ClinicalTrials.gov, last updated 2026-05-04.

Sponsored by Faculty of Dental Medicine for Girls · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
100
Allocation
Randomized
Ages
16 Years to 45 Years
Sex
All
01

Study summary

This randomized placebo-controlled trial evaluated the effectiveness of zinc oxide ointment in the treatment of recurrent aphthous stomatitis (RAS). The study included 100 patients randomly assigned to receive either zinc oxide ointment or a placebo, applied three times daily for six days. Pain intensity was measured using a visual analogue scale (VAS), and oral health-related quality of life was assessed using OHIP-14 at baseline and on days 1, 3, and 6.

Read the detailed description

This randomized, placebo-controlled clinical trial investigated the efficacy of topical zinc oxide ointment in the management of recurrent aphthous stomatitis (RAS). A total of 100 participants diagnosed with RAS were enrolled and randomly assigned in equal proportions to either the intervention group receiving zinc oxide ointment or the control group receiving a placebo formulation. The study medication was applied topically three times daily for a duration of six consecutive days.

Clinical outcomes were assessed at baseline and on days 1, 3, and 6 post-treatment initiation. Pain intensity was evaluated using a visual analogue scale (VAS), while oral health-related quality of life was measured using the Oral Health Impact Profile (OHIP-14). Additional clinical observation included assessment of ulcer size and surrounding erythematous halo.

02

Conditions studied

  • Recurrent Aphthous Stomatitis

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Keywords

  • Zinc Oxide
  • Recurrent Aphthous Stomatitis
  • Treatment
03

Who can participate

Ages eligible
16 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • -Systemically healthy subjects suffering from minor oral RAS.
  • Patients of both sexes, aged 16-45 years (to avoid the potential effects of age on healing).
  • Participants had not received any treatment for the ulcers before being included in the study and had no active periodontitis.
  • Ulcers are of a duration of less than 48 hours.

Exclusion criteria

Exclusion Criteria:

  • -Participants with removable prosthetic or orthodontic appliances (to avoid potential effects on healing).
  • Tobacco chewers, smokers or alcoholics.
  • Pregnant or lactating females.
  • Patients who had previously or are presently taking medications that could affect events associated with the healing process (erg, corticosteroids, oral antidiabetics, non-steroidal anti-inflammatory drugs, immune-modulating agents).
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
100 participants (actual)

Study arms

  • Experimental
    Znic Oxide Ointment group

    Participants administrated Zinc Oxide Ointment 3 times for 7days. Participants instructed to apply ointment after drinking and eating.

    Drug: zinc oxide

  • Placebo comparator
    Placebo

    Placebo ointment was administered by this group; it was prepared the same as the test ointment, without zinc oxide.

    Drug: Placabo

Interventions

  • Drugzinc oxide

    zinc oxide ointment that was formulated as in a polyethylene glycol base. The prepared ointment was evaluated for organoleptic properties such as odor, color, pH, smoothness, and spread ability

    Also known as: Medicated ointment

  • DrugPlacabo

    A topical placebo ointment that was prepared the same as the test ointment without zinc oxide.

    Also known as: Ointment without Zinc Oxide

05

What researchers measure

Primary outcomes

  1. Visual analog scale

    A Visual Analog Scale (VAS) is a subjective, validated, 100mm (or 10cm) straight-line tool used in healthcare to measure pain intensity, fatigue, or other sensations. Patients mark their sensation level between "no pain" (0) and "worst pain imaginable" (100). It is highly sensitive for tracking changes in symptoms over time

    Time frame: Before treatment ,Day 1,Day 3 and Day 6

Secondary outcomes

  1. Diameter of the ulcer

    Measurement of erythematous halo diameter and whitish base

    Time frame: Day before treatment,1st day,3rd day and 6th day

  2. OHIP-14

    Oral health impact 14 questionnaire Secondary outcome: Oral health-related quality of life assessed using the validated Oral Health Impact Profile-14 (OHIP-14), with scores ranging from 0 to 56, where higher scores indicate poorer quality of life.

    Time frame: At day 6

06

Study locations

1 site
  • Faculty of Dental Medicine for Girls ,Al-Azhar university
    Cairo, Cairo Governorate 11651, Egypt
07

References and documents

Publications

  • El-Wakeel NM, Dawoud MHS. Topical insulin-liposomal formulation in management of recurrent aphthous ulcers: A randomized placebo-controlled trial. J Investig Clin Dent. 2019 Nov;10(4):e12437. doi: 10.1111/jicd.12437. Epub 2019 Jul 27. PubMed 31350870 ↗
  • Ghorbani A, Akbari J, Boorboor M, Nekoukar Z, Eslami G. Evaluation of zinc sulfate mucoadhesive formulation on recurrent aphthous stomatitis: a randomized double-blind, placebo-controlled clinical trial. BMC Oral Health. 2020 Jul 28;20(1):212. doi: 10.1186/s12903-020-01194-4. PubMed 32723352 ↗
  • Halboub E, Al-Maweri SA, Parveen S, Al-Wesabi M, Al-Sharani HM, Al-Sharani A, Al-Kamel A, Albashari A, Shamala A. Zinc supplementation for prevention and management of recurrent aphthous stomatitis: a systematic review. J Trace Elem Med Biol. 2021 Dec;68:126811. doi: 10.1016/j.jtemb.2021.126811. Epub 2021 Jun 12. PubMed 34146924 ↗
  • Estornut C, Rinaldi G, Carceller MC, Estornut S, Perez-Leal M. Systemic and local effect of oxidative stress on recurrent aphthous stomatitis: systematic review. J Mol Med (Berl). 2024 Apr;102(4):453-463. doi: 10.1007/s00109-024-02434-8. Epub 2024 Feb 20. PubMed 38376817 ↗
  • Parssinen M, Jasberg H, Mikkonen JJW, Kullaa AM. Oral mucosal pellicle as an immune protection against micro-organisms in patients with recurrent aphthous stomatitis: A hypothesis. Med Hypotheses. 2021 Jan;146:110449. doi: 10.1016/j.mehy.2020.110449. Epub 2020 Dec 11. PubMed 33359920 ↗
  • Al-Maweri SA, Halboub E, Al-Sharani HM, Shamala A, Al-Kamel A, Al-Wesabi M, Albashari A, Al-Sharani A, Abdulrab S. Association between serum zinc levels and recurrent aphthous stomatitis: a meta-analysis with trial sequential analysis. Clin Oral Investig. 2021 Feb;25(2):407-415. doi: 10.1007/s00784-020-03704-8. Epub 2021 Jan 6. PubMed 33409687 ↗
  • Kounoupis V, Andreadis D, Georgaki M, Albanidou-Farmaki E, Daniilidis M, Markopoulos A, Karyotis N, Nikitakis NG, Poulopoulos A. IL-10 and TGF-beta1 gene polymorphisms in Greek patients with recurrent aphthous stomatitis. Med Oral Patol Oral Cir Bucal. 2022 Sep 1;27(5):e426-e433. doi: 10.4317/medoral.25352. PubMed 35660731 ↗
  • Silva TM, Bolzan TCA, Zanini MS, Alencar T, Rodrigues WD, Bastos KA, Severi JA, Resende JA, Villanova JCO. Development and Evaluation of a Novel Oral Mucoadhesive Ointment Containing Pomegranate Peel Extract as an Adjuvant for Oral Hygiene of Dogs. J Vet Dent. 2020 Sep;37(3):133-140. doi: 10.1177/0898756420973470. Epub 2020 Nov 25. PubMed 33234003 ↗

Individual participant data

Plan to share: No — This study investigated whether zinc oxide (ZnO) ointment can help reduce pain and improve healing in patients with recurrent aphthous ulcers (mouth ulcers). One hundred participants were divided into two groups: one received ZnO ointment and the other received a placebo. The treatment was applied three times daily for six days. Pain levels and oral health impact were measured before and after treatment. The results showed that ZnO ointment helped reduce pain faster in the early days compared to placebo, but there was no significant difference in overall quality of life after six days.

08

Registry details

Key details

Study ID
NCT07565181
Lead sponsor
Faculty of Dental Medicine for Girls
Collaborators
Cairo University
Responsible party
Esraa hamdy (Dental student, Faculty of Dental Medicine for Girls) — Principal investigator
First posted
May 4, 2026
Start date
Jun 30, 2025
Primary completion
Jan 30, 2026
Completion
Mar 30, 2026
Last update
May 4, 2026

Study contacts

Naglaa M. El-Wakeel, PhD
principal investigator · Al Azhar University for girls

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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