Comparison of Topical Photodynamic Therapy With Topical Calcipotriol in Management of Oral Leukoplakia

NCT07453472 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: PDT CALCI HOL 2025
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

Brief Summary

(i)Rationale/ gaps in existing knowledge,: Oral cancer, one of the top three common cancers in India is usually preceded by Oral potentially malignant disorders in nearly two thirds of the cases like Oral leukoplakia. OL has a high prevalence and malignant transformation rates(0.13% - 40.8%). There are no universal protocols for management in OL ranging from preventive, conservative, medical and surgical interventions. They all have limitations and high recurrence rates requiring regular follow up. (ii)Novelty: Removal of pathological lesions are believed to reduce the risk of malignant transformation in OL. Surgical methods are associated with morbidity and high recurrence rates. Non -invasive methods (like Photodynamic therapy) that can remove the abnormal lesions would be preferred as they are cheaper, convenient, safe with less morbidity and better patient acceptability. They also have the advantage of repeatability with minimum morbidity and damage to adjacent normal tissues. Non -invasive medical management involves topical application of retinoids which are associated with systemic toxicity, recurrence and development of resistance. (iii)Objectives, Primary objective: To compare the effect of 2.5% Toluidine blue mediated topical photodynamic therapy and topical calcipotriol (0.005%) on clinical response after completion of treatment at 4 weeks from baseline during management of Oral leukoplakia Secondary objectives: To compare the effect of 2.5% Toluidine blue mediated topical photodynamic therapy with topical Calcipotriol (0.005%) on lesion size, lesion roughness/ whiteness, and oral health quality of life after completion of treatment at 4 weeks and 12 weeks from baseline during management of Oral leukoplakia To compare the effect of 2.5% Toluidine blue mediated topical photodynamic therapy with topical Calcipotriol (0.005%) on salivary molecular markers ( IL6, TNF-α, PCNA, Survivin and VEGF) after completion of treatment at 4 weeks from baseline To compare the adverse events, time to complete response and recurrence rates between the two groups (iv)Methods,: An open label randomized clinical trial where Group A (n=83) will receive 4 sessions of Toludine blue mediated photodynamic therapy (Fluence 15J/cm2); GroupB (n=83) will receive twice daily tropical application of Calcipotriol (0.005%) over a period of 4 weeks. The clinical response, lesion thickness/ whiteness, lesion size /area, OHIP-14 scores, adverse events and recurrence rates will be compared with baseline at 4 weeks and 12 weeks after completion of therapy. Sterile PVA ophthalmic sponges will be used to evaluate molecular markers ( IL6, TNF-α, PCNA, Survivin VEGF) from treatment site of lesion at baseline and 4 weeks after completion of treatment by ELISA. The data will be analyzed statistically using Intention to treat and as per protocol analysis at significance levels of p\<0.05. (v)Expected outcome.: The study will validate and verify the effectiveness of the TB mediated PDT protocol in the management of OL as compared to other non invasive method of topical Calcipotriol in terms of clinical response ( complete/ partial/ none), lesion thickness/ whiteness, lesion size and it's effect on oral health quality of life. Adverse events if any and recurrence rates or malignant transformation rates will also help in assessment of safety of the protocol. The molecular markers will help to monitor and determine prognosis of the lessons following treatment.

Conditions

Oral Leukoplakia

Keywords

Oral leukoplakia; photodynamic therapy; photosensitizers; calcipotriol; assessment; patient outcomes; biology molecular

Outcome Measures

Primary Outcomes (1)

• Clinical response: Number of patients with Complete response/ Partial response/ No response/ alteration in clinical pattern

  a. Clinical response(Chen et al 2021)(42): 1. complete remission of the lesion clinically evaluated; Complete Response CR 2. partial reduction of at least 20% in the total diameter of the lesion; Partial response PR 3. reduction of the lesion by less than 20% in diameter; No Response NR 4. alteration in the clinical pattern of the lesion (homogeneous and non- homogeneous).

  Baseline, 4 weeks, 12 weeks

Secondary Outcomes (4)

• Lesion size

  Baseline, 4 weeks, 12 weeks

• Lesion roughness/ whiteness: Number of patients with total resolution/ Moderate resolution/ Minimal change/ No visible change

  Baseline, 4 weeks, 12 weeks

• Oral Health quality of Life: Number of patients with OHIP-14 scores 0-8

  baseline, 4 weeks, 12 weeks

• Concentration of salivary molecular markers ( IL6, TNF-α, PCNA, Survivin and VEGF)

  Baseline, 4 weeks

Other Outcomes (2)

• time to complete response

  up to 12 weeks

• Oral pain/ burning sensation scores 0-10

  upto 4 weeks

Study Arms (2)

Photodynamic therapy

EXPERIMENTAL

Non-invasive PDT using LED of wavelength ranging from 630-660nm( Fluence 15 J/cm2) as light source and 2.5% TB as photosensitizer will be used in oral leukoplakia once a week for 4 weeks along with preventive and conventional therapy

Other: Non-invasive Photo Dynamic Therapy using LED of wavelength ranging from 630-660nm( Fluence 15 J/cm2) as light source and 2.5% TB as photosensitizer; Other: Conventional non-invasive management : All subjects in the two groups will receive the same standard conventional non- invasive management advised for OL as per current scientific evidence

Topical Calcipotriol

ACTIVE COMPARATOR

Topical application of Calcipotriol ointment 0.005% twice a day for 4 weeks in oral leukoplakia along with preventive and conventional therapy

Drug: Topical application of Calcipotriol ointment 0.005% twice a day for 4 weeks along with preventive and conventional therapy; Other: Conventional non-invasive management : All subjects in the two groups will receive the same standard conventional non- invasive management advised for OL as per current scientific evidence

Interventions

Topical application of Calcipotriol ointment 0.005% twice a day for 4 weeks along with preventive and conventional therapy DRUG

Topical retinoids have been more commonly used in oral leukoplakia and are associated with relapses, toxicity and photosensitivity

Topical Calcipotriol

Conventional non-invasive management : All subjects in the two groups will receive the same standard conventional non- invasive management advised for OL as per current scientific evidence OTHER

Both Groups A and b will receive conventional non-invasive management as per current scientific evidence

Also known as: Conventional non-invasive management

Photodynamic therapy; Topical Calcipotriol

Non-invasive Photo Dynamic Therapy using LED of wavelength ranging from 630-660nm( Fluence 15 J/cm2) as light source and 2.5% TB as photosensitizer OTHER

Choice of LED light source instead of morecommonly used lasers and 2.5% Toludine blue as photosensitizer for photodynamic therapy instead of 5ALA in Oral leukoplakia

Photodynamic therapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All diagnosed cases of Oral Leukoplakia with size ≥ 2 cm2 (Van der Waal classification ≥ L2) reporting to the department of OMR, CDER and willing to participate in the study will be included
• Subjects clinically and histologically diagnosed as Oral Leukoplakia.
• Subjects \> 18 years of age.
• Subjects willing to participate in the study and to complete the treatment sessions.

You may not qualify if:

• History of any topical and/or systemic therapy for Oral Leukoplakia other than general management in last 2 months.
• Subjects with current or past history of malignancy.
• Subjects with any lesion suspicious of malignancy requiring biopsy.
• Subjects with severe dysplasia and carcinoma in situ on biopsy of oral lesion
• Subjects with history of hyperphotosensitivity (genetic disorders, dermatological conditions, drug induced, systemic conditions)
• Subjects with calcium, Vit D metabolic and parathyroid disorders
• Pregnant and lactating females.

Sponsors & Collaborators

• Dr. Shalini Gupta: lead
• All India Institute of Medical Sciences: collaborator

Study Sites (1)

All India Institute of Medical Sciences New Delhi

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

Location

Related Publications (1)

• Pietruska M, Sobaniec S, Bernaczyk P, Cholewa M, Pietruski JK, Dolińska E, et al. Clinical evaluation of photodynamic therapy efficacy in the treatment of oral leukoplakia. PhotodiagnosisPhotodyn Ther. 2014 Mar;11(1):34-40. Bhandari A, Budakoti A, Chaudhary M. Methylene Blue-mediated Photodynamic Therapy for the Treatment of Oral Leukoplakia. Journal of the Scientific Society. 2023 Dec;50(3):394. Silva BS de F, Rocha RM, Prudente TP, Lenza MM de O, Ferraz DLF, Mezaiko E, et al. Efficacy of 5% methylene blue photodynamic therapy in the treatment of potentially malignant oral disorders: a randomized, double-blind, controlled trial. International Journal of Clinical Trials. 2024 Jul 25;11(3):207-14. Selvam NP, Sadaksharam J, Singaravelu G, Ramu R. Treatment of oral leukoplakia with photodynamic therapy: A pilot study. J Cancer Res Ther. 2015;11(2):464-7. Ghalwash D, Mahmoud E, Shaker O. Evaluation of the therapeutic effect of topical calcipotriol versus topical tretinoin in treatment of oral Leukoplakia and their effect on clinical improvement and salivary level of MMP-9, IL-6 and TGF-β: A Randomized Clinical Trial. Egyptian Dental Journal. 2017 Jul 1;63(3):2441-57. Femiano F, Gombos F, Scully C, Battista C, Belnome G, Esposito V. Oral leukoplakia: open trial of topical therapy with calcipotriol compared with tretinoin. Int J Oral Maxillofac Surg. 2001 Oct;30(5):402-6.

  BACKGROUND

MeSH Terms

Conditions

Leukoplakia, Oral

Interventions

Photosensitizing Agents

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)

Dermatologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Radiation-Sensitizing Agents

Study Officials

• Shalini Gupta, MDS, FDSRCS(Edin), FAAOM, MBA

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shalini Gupta, MDS,FDSRCS(Edin), FAAOM, MBA

CONTACT

919971904592; shalinigupta@hotmail.com

Savita Yadav, PhD

CONTACT

919811797161; savita11@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The outcome assessors for the molecular biomarkers will be masked to the identity of the groups
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: An open label parallel arm Randomized clinical trial

Study Record Dates

• First Submitted: February 23, 2026
• First Posted: March 6, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 3 years after publication of results
• Access Criteria: Any academic/ scientific enquiry about methodology and results of the trial from researchers in the field can be accessed from the information in the publication or on reasonable request via email (shalinigupta@hotmail.com) to principal investigator

Locations

IN (1)