A Phase 1/2 interventional study of Metformin Hydrochloride and betamethasone dipropionate in Oral Submucous Fibrosis, sponsored by Ziauddin University. Completed at 1 site in Pakistan. Open to participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2025-05-02.
Sponsored by Ziauddin University · Phase 1/2, Interventional, and Treatment
OSF is a widespread health issue in Asian countries, notably Pakistan, linked to the consumption of pan, chalia, and gutka, affecting a rising number of young individuals as an epidemic. This condition significantly impairs oral function, resulting in ulcers and chronic lesions, often progressing to oral cancer. Current treatments focus on symptom relief and halting disease progression. This study explores the repurposing of metformin, an FDA-approved drug with antifibrotic properties, for OSF treatment. Our objective is to unveil its therapeutic potential and comprehend its impact on the dysregulated signaling pathways associated with OSF. This research offers promising insights for an enhanced management approach, providing hope for those grappling with this debilitating condition
OSF stands as a persistent inflammatory and potentially malignant condition affecting the oral cavity, marked by progressive fibrosis of the oral mucosa. The spectrum of its manifestations spans from initial inflammation to the gradual emergence of fibrous bands, leading to restricted mouth opening and mucosal rigidity. Common symptoms encompass burning sensations, difficulty in swallowing, and alterations in taste perception. This health concern has gained prominence in Pakistan, experiencing a worrisome surge in prevalence from 8.3/105 to 16.2/105 in recent years. Formerly confined to Southeast Asia, OSF has now transcended borders, manifesting in Asian immigrant communities in Britain and America, evolving into a global oral potential malignant disorder (OPMD) with a malignant rate of 9.13% .
Presently, the corticosteroid-based approach effectively reduces inflammation in OSF but falls short in addressing the underlying molecular mechanisms contributing to fibrosis. Furthermore, the prolonged use of corticosteroids raises concerns about adverse effects, including mucosal atrophy and compromised tissue integrity. This study aims to investigate the potential of metformin, a recognized emerging drug for treating fibrosis, and its anti-fibrotic properties in various organs. The established safety profile of metformin adds an advantageous aspect to its potential applications.
Numerous studies indicate that metformin exhibits anti-fibrotic effects by inhibiting TGF-β1 production, reducing phosphorylation and nuclear translocation of Smad2/3. Additionally, metformin inhibits Smad2/3 phosphorylation independently and activates AMPK, hindering Smad3 phosphorylation. The impact on reactive oxygen species (ROS) generation moderates TGF-β1-induced Smad2/3 phosphorylation and myofibroblast differentiation.Metformin has shown promise in hindering collagen production and promoting trans differentiation in various organ, including the lung, kidney, heart and adipose tissue. A clinical trial reported metformin therapy's impact on postmenopausal ovaries, patients with type 2 diabetes mellitus (T2DM) exhibited isotropic collagen organization and reduced fibrosis during oophorectomy.The observed risk reduction for ovarian cancer in T2DM women using metformin suggests its potential as an ovarian cancer prophylaxis. Despite conflicting clinical trial results in liver fibrosis, metformin consistently improves hepatocyte damage and inflammation. Clinical trials have explored the role of metformin antitumor activity when combined with conventional chemotherapeutic drugs and in idiopathic pulmonary fibrosis it inhibits TGFβ1, suppressing collagen formation, activating PPARγ signaling and inducing lipogenic differentiation.
3,255 studies on the registry are indexed under Fibrosis; 465 are open to participants now.
This study's enrollment of 30 is below the median of 50 across 2,130 interventional studies indexed under Fibrosis.
Browse Fibrosis studies →Ziauddin University is the lead sponsor of 48 studies on the registry; 9 are open to participants now.
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Exclusion Criteria:
Group 1: Standard treatment with topical cream betamethasone and Pentoxifylline tablet.
Drug: betamethasone dipropionate · Drug: Pentoxifylline
Metformin 500 mg thrice daily.
Drug: Metformin Hydrochloride
Topical cream metformin thrice daily
Drug: Metformin Hydrochloride
Group B will receive Metformin 500 mg thrice daily. Group C will receive topical cream metformin thrice daily.
Also known as: Glucophage
Group 1will recieve topical cream betamethasone thrice daily
Also known as: Betnovate
Group 1 will receive Pentoxifylline tablet 400 mg twice daily
Also known as: Trental
Cell Viability
Cell Viability by MTT Assay Unit: Percentage Assessment of cell viability will be reported as a percentage of untreated control cells.
Time frame: 8 months
Cytotoxicity
Cytotoxicity Unit: Percentage Measurement of cytotoxicity will be presented as a percentage relative to untreated control cells.
Time frame: 8 Months
Morphological Changes Cell Shape
Unit: Qualitative description Cell shape alterations will be described qualitatively based on microscopic observations.
Time frame: 8months
Morphological Change Cell Density
Unit: Cells per unit area Changes in cell density will be quantified and reported as cells per unit area. Sub-Measure 3: Extracellular Matrix (ECM) Structure Unit: Qualitative description Alterations in ECM structure will be qualitatively assessed.
Time frame: 8 months
Morphological Change Extracellular Matrix (ECM) Structure
Extracellular Matrix (ECM) Structure Unit: Qualitative description Alterations in ECM structure will be qualitatively assessed.
Time frame: 8 months
Cell Migration Assays
Unit: Distance migrated (micrometers) The extent of cell migration will be quantified as the distance migrated from the original point.
Time frame: 8months
Cell Invasion Assays
Unit: Invaded area (e.g., square millimeters) Assessment of cell invasion will be presented as the invaded area relative to untreated control cells.
Time frame: 8 months
Apoptosis Analysis
Unit: Percentage Apoptotic cells will be quantified and reported as a percentage of the total cell population.
Time frame: 8months
Assess Signaling pathway with optimal metformin concentration
To evaluate the effect of TGF-beta Smad 2/3 and wnt/b-catenin signaling pathways in vitro
Time frame: 9 months
Clinical Oral Mucosal Characteristics
Unit: Descriptive score (based on a scale ranging from 0 to 3 (normal to severe).0=No changes 1=Soreness 2=Soreness and ulceration 3=Soreness, ulceration and ability to use a liquid diet only
Time frame: 9 months
Patient Burning sensation pain
Unit: Units on a scale (Verbal numeric rating scale graded on a 10-point scale from 0 to 10, where 0 indicated no burning sensation while 10 represented the worst burning sensation)
Time frame: 9 months
Patient Mouth Opening
Unit: Millimeters on a scale of Grade 0 = \> 35 mm, Grade1= 26-35mm, Grade 2= 15-25mm, Grade 3: \< 10mm
Time frame: 9 months
Plan to share: No — The decision not to share Individual Participant Data (IPD) may be based on several considerations and could be influenced by institutional policies, ethical guidelines, and practical constraints.Sharing individual-level data may risk the identification of study participants, even with anonymization efforts, especially in smaller studies or specific populations
This study is completed, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.
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Oral Submucous Fibrosis
Ziauddin University