Candida Associated Cytokines in Oral Leukoplakia

NCT04712929 | Completed

• 1 other identifier: A-634
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine the correlation between candida and pro- inflammatory cytokines response in Oral Leukoplakia(OL) with antifungal therapy. Ethical clearance from the Institutes ethical committee and Informed written consent from the patient will be obtained. The study group would comprise of clinically and histopathologically confirmed cases of OL (60 patients). The control group would be 30 dental patients ( age \& sex matched) who do not any malignancy, OL or any other potentially malignant disorder of oral mucosa. Patients who have any predisposing factor for oral candidiasis will be excluded from the study. Swabs will be taken from the oral lesion and cultured for candida to determine phenotypes, virulence attributes and antifungal sensitivity. Sterile PVA opthalmic sponges will be used to collect sample from the surface of oral epithelium and then processed to determine levels of pro- inflammatory cytokines (IL-6, IL-8. IL-17, TNFα). This procedure will be repeated in study group 2 weeks after a course of antifungal therapy. The results will be tested statistically at a confidence level of 95%.

Conditions

Oral Leukoplakia

Keywords

Candida; oral leukoplakia; il 6; il 8; il 17; TNF alpha; aspartyl proteinase; biofilm formation; phospholipase; antifungal sensitivity

Outcome Measures

Primary Outcomes (11)

• Oral burning sensation

  VAS score (0-10)

  Before and after antifungal treatment (2 weeks)

• Clinical size of lesion

  maximum Length( L) and width (W) L1: L/W ≤ 2 cm L2: L /W 2-4 cm L3: L/W ≥ 4cm

  Before and after antifungal treatment (2 weeks)

• Pro- inflammatory cytokines

  il6,il8,il17,TNF-alpha by ELISA before and after antifungal treatment

  Before and after antifungal treatment (2 weeks)

• Erythema of oral lesion

  Scores as \[ 0- no change, 1- minimal change ( Reduction in erythema \< 1cm of oral lesion, and 2- significant change( Reduction in erythema ≥ 1cm of oral lesion)

  Before and after antifungal treatment (2 weeks)

• Thickness of oral lesion

  Scores as \[ 0- no change, 1- minimal change ( Reduction in thickness \< 1cm of oral lesion, and 2- significant change( Reduction in thickness ≥ 1cm of oral lesion)

  Before and after antifungal treatment (2 weeks)

• candida positivity

  Swabs for smear or culture positive for Candida

  before antifungal treatment

• Phospholipase Activity of Candida in Oral leukoplakia

  Phospholipase activity (Pz) was measured by dividing colony diameter by the diameter of the precipitation zone (Pz) around the colony formed on the plate. A Precipitation zone (in mm) around colony 1.0 : 0 negative (-), 0.99-0.9 : 1 weak (+), 0.89-0.8: 2 poor (++), 0.79-0.7: 3 moderate (+++), \< 0.69: 4 Strong positive(++++),

  Before antifungal therapy

• Secreted aspartyl proteinase activity of Candidain Oral leukoplakia

  Secreted aspartyl proteinase activity was measured by dividing colony diameter by the diameter of the precipitation zone (Pz) around the colony formed on the plate. A Precipitation zone (in mm) around colony 1.0 : 0 negative (-), 0.99-0.9 : 1 weak (+), 0.89-0.8: 2 poor (++), 0.79-0.7: 3 moderate (+++), \< 0.69: 4 Strong positive(++++),

  Before antifungal therapy

• Biofilm formation

  Absorbance values of test wells at 490nm of XTT reduction assay- absorbance values of control

  Before antifungal therapy

• Antifungal sensitivity

  Using CLSI document M44-A for disk diffusion method for Fluconazole (25 μg), Voriconazole (1 μg) and Clotrimazole (50 μg) S: Sensitive R: Resistant I: Intermediate

  Before antifungal therapy

• Histopathology

  Mild Dysplasia Moderate Dysplasia Severe Dysplasia PAS stain positive/ negative

  Before antifungal therapy

Secondary Outcomes (1)

• Malignant transformation

  after 2,5,7,10 years

Study Arms (3)

Homogenous oral leukoplakia

uniform, flat, thin, smooth/ wrinkled/corrugated surface throughout the white lesion. Tab Fluconazole 100 mg as a mouthwash ( tablet dissolved in 10 ml of drinking water and used as a mouth rinse for 2 minute and swallowed) once a day for 14 days

Other: Fluconazole

Non-Homogenous oral leukoplakia

mixture of red and white lesions with a irregularly speckled/ nodular/ verrucous surface Tab Fluconazole 100 mg as a mouthwash ( tablet dissolved in 10 ml of drinking water and used as a mouth rinse for 2 minute and swallowed) once a day for 14 days

Other: Fluconazole

Control group

30 healthy controls ( age and sex matched) would also be recruited from patients who are reporting for other routine dental problems.

Interventions

Fluconazole OTHER

( Tab Fluconazole 100 mg as a mouthwash ( tablet dissolved in 10 ml of drinking water and used as a rinse for 2 minute and swallowed) once a day for 14 days WHO criteria 5As and 5Rs for tobacco cessation

Also known as: Behavioral intervention for tobacco/ betel nut / alcohol cessation

Homogenous oral leukoplakia; Non-Homogenous oral leukoplakia

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The patients in the study group and control group will be consecutively recruited from the Oral Medicine \& Radiology clinic at Centre for Dental Education \& Research AIIMS.

You may qualify if:

• clinically and histologically confirmed cases of Oral Leukoplakia would be prospectively recruited for this study who have not been under treatment for the same for past 6 months.
• healthy controls ( age and sex matched) would also be recruited from patients who are reporting for other routine dental problems.
• Also these patients would be those who have good oral hygiene (simplified oral hygiene index score 0-3, periodontal screening and recording PSR code 0-2) and do not have any potentially malignant disorder of the oral mucosa or oral squamous cell carcinoma and have no systemic diseases or any other malignancy.

You may not qualify if:

• Patients with history of significant and serious uncontrolled systemic disease allergy to antifungals or history of antifungal therapy in past 6 months.
• Patients with history of any other malignant disease.
• Children ( age \< 18 years) and pregnant women.
• Patients with history of major/ minor surgery and predisposing factors for oral candidal infection like diabetes/ endocrine disorders, xerostomia, poor oral hygiene, removable prosthesis, prolonged corticosteroid/ antibiotic/ immunosuppressant/ antibacterial mouthwash therapy, radiation/ chemotherapy, auto immune disorders and primary / secondary immune deficiencies, nutritional deficiencies and hospitalized debilitated patients.

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead

Study Sites (1)

All india Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Related Publications (1)

• Gupta SR, Gupta N, Sharma A, Xess I, Singh G, Mani K. The association of Candida and antifungal therapy with pro-inflammatory cytokines in oral leukoplakia. Clin Oral Investig. 2021 Nov;25(11):6287-6296. doi: 10.1007/s00784-021-03927-3. Epub 2021 Apr 4.

  PMID: 33813637 DERIVED

MeSH Terms

Conditions

Leukoplakia, Oral; Torulopsis

Interventions

Fluconazole; Behavior Therapy; Tobacco Products; Catechin; Ethanol

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Leukoplakia; Precancerous Conditions; Mouth Diseases; Stomatognathic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Psychotherapy; Behavioral Disciplines and Activities; Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture; Chromans; Benzopyrans; Pyrans; Flavonoids; Chromones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alcohols; Organic Chemicals

Study Officials

• Shalini Gupta, MDS,FDSRCS

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: January 19, 2021
• Study Start: November 1, 2018
• Primary Completion: February 15, 2020
• Study Completion: March 30, 2020
• Last Updated: January 20, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)