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Oral Submucous FibrosisPhase 1/2"FIBR-MET-PF"NCT06871904

Fibrosis-Modulating Effects of Metformin and Pirfenidone in Oral Submucous Fibrosis

A Phase 1/2 study testing Metformin Hydrochloride 500Mg Tablet, Pirfenidone (PFD) and Beclomaethasone and Vitamin E in people with Oral Submucous Fibrosis, run by Ziauddin University at 1 site in Pakistan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The goal of this clinical trial is to learn if metformin and antifibrotic drugs (pirfenidone) can modulate fibrosis and improve treatment outcomes in patients with oral submucous fibrosis (OSF). Read more about this study

Who is it for?
Ages 18 to 45 years
Conditions the study is for
Oral Submucous Fibrosis
What is being tested?
Metformin Hydrochloride 500Mg Tablet, Pirfenidone (PFD) and Beclomaethasone and Vitamin E
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 sitePakistan
Study dates
7 Apr 2025to 30 Dec 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Patients with OSF having fibrous bands
  • Patients with limited mouth opening due to OSF in Stage 2 and Stage 3
  • Patients who have not received any treatment for OSF in the previous three months
  • Patients with habits of pan, Chalia, Gutkha
  • The age group between 18 and 45 years

Who cannot join

  • Patients presenting with OSCC
  • Patients with limited mouth opening due to impaction of the third molar
  • Patients with limited mouth opening due to temporomandibular joint disorder
  • Any history of Metformin intolerance or contraindications to its use.
  • Medical conditions (e.g., cardiovascular disease, renal/hepatic impairment) or drug therapy (>6 months) with immunosuppressants, corticosteroids, or antifibrotics.
  • Pregnancy or lactation.
  • Participation in other clinical trials concurrently.
  • Inability / unwilling to provide informed written consent.

Trial locations and contacts

1 site in 1 country.

Pakistan1 site

  • Ziauddin University

    Karachi, Sindh, 74700

Other trials in Pakistan

About this study

Official title: Exploring the Fibrosis-Modulating Potential of Metformin and Pirfenidone in Oral Submucous Fibrosis: Molecular Mechanisms to Clinical Applications

The goal of this clinical trial is to learn if metformin and antifibrotic drugs (pirfenidone) can modulate fibrosis and improve treatment outcomes in patients with oral submucous fibrosis (OSF). The study also aims to investigate the molecular mechanisms underlying their effects on exosome secretion and protein expression.

The main questions it aims to answer are:

Read more

Do metformin and antifibrotic drugs alter exosome secretion and biological activity in OSF cell lines? What molecular pathways are influenced by these drugs in modulating fibrosis? Does treatment with metformin and antifibrotic drugs improve clinical outcomes in OSF patients? Researchers will compare metformin and antifibrotic drug treatment groups to a control group to see if these drugs lead to significant changes in fibrosis-related exosomal protein expression and clinical improvement in OSF patients.

Participants will :

Undergo in vitro experiments on OSF cell lines to analyze drug effects using qPCR, Western Blot, and LCMS for protein profiling.

Participate in a randomized, double-blind clinical trial where they receive metformin, antifibrotic drugs, or a placebo.

Undergo clinical evaluations and laboratory tests to assess treatment efficacy. This study aims to develop an affordable and effective fibrosis-targeted therapy for OSF by repurposing metformin, potentially improving patient outcomes and reducing the risk of malignant transformation.

Read the detailed description

Oral submucous fibrosis stands as a persistent inflammatory and potentially malignant condition affecting the oral cavity, marked by progressive fibrosis of the oral mucosa. Existing therapies, such as corticosteroids, are costly and merely treat the symptoms without addressing the molecular pathways that cause fibrosis, which results in limited efficacy, relapse, and side effects. Given the financial constraints of affected communities, there is a desperate need for affordable and accessible treatments. This research project aims to investigate the effects of metformin and antifibrotic drugs on the secretion and biological activity of exosomes in oral submucous fibrosis (OSF) cell lines. The study will explore how these treatments impact morphological changes, exosomal gene expression, and protein profiles in OSF cell lines compared to control and vehicle-controlled groups. Additionally, the project will identify molecular pathways influenced by metformin and antifibrotic drugs, with a focus on their modulation of exosomal protein content and functional profiles. The clinical relevance of exosomal protein profiles in OSF treatment, particularly through the repurposing of metformin, will also be evaluated. Methodologically, the study involves in vitro experiments on OSF cell lines, employing techniques such as qPCR, Western Blot, and Liquid Chromatography-Mass Spectrometry (LCMS) for protein profiling, alongside a clinical trial to assess therapeutic efficacy.

The project is structured around several key objectives:

  1. Impact Assessment: Evaluate how metformin and antifibrotic drugs affect exosome secretion and activity in OSF cell lines.
  2. Morphological and Gene Expression Analysis: Analyze morphological changes and exosomal gene expression profiles in OSF cell lines post-treatment compared to control groups.
  3. Molecular Pathways: Identify and analyze the molecular pathways modulated by metformin and antifibrotic drugs that influence exosomal protein content and functions.
  4. Exosome Characterization: Characterize exosomes isolated from different treatment groups using advanced techniques such as dynamic light scattering (DLS), scanning electron microscopy (SEM), Western Blot (WB) and Liquid Chromatography-Mass Spectrometry (LCMS).
  5. Clinical Relevance: Explore the potential clinical applications of the exosomal protein profiles for OSF treatment, focusing on the repurposing of metformin.
  6. Methodology: The study includes both in vitro and clinical components, with the in vitro studies involving dose-response experiments, microscopy, gene expression analysis, and exosome isolation and characterization. The clinical trial will assess the efficacy of metformin and antifibrotic drugs in patients with OSF through randomized double-blind controlled trials.

This research has the potential to uncover new therapeutic strategies for OSF, particularly through the repurposing of metformin, which could lead to better clinical outcomes for patients suffering from this precancerous condition.

Being tested
Metformin Hydrochloride 500Mg Tablet, Pirfenidone (PFD), Beclomaethasone and Vitamin E
Keywords
Oral submucous fibrosis, Fibrosis Modulation, Metformin, Pirfenidone, Exosome secretion, Molecular Pathway, LCMS, Clinical Trial, Exosome Protein Profiling
Medical subject headings
Oral Submucous Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Metformin Hydrochloride 500Mg TabletDrug

    Also called Glucophage

    Metformin 500 mg is being tested for its potential role in treating oral submucous fibrosis (OSF) due to its antifibrotic and anti-inflammatory effects. This intervention will be administered orally at a dose of 500 mg twice daily (OD) for a specified 6 months treatment period for Group 2 .

    Metformin activates AMPK (AMP-activated protein kinase), which inhibits TGF-β signaling and collagen deposition, reducing fibrosis and inflammation.

    Distinction from Other Arms: Unlike Pirfenidone, which directly targets profibrotic cytokines, Metformin modulates metabolic pathways to exert antifibrotic effects. The Control Group will receive supportive care for OSF.

  • Pirfenidone (PFD)Drug

    Also called Pirfibet

    Pirfenidone 200 mg (Pirfibet by Mactor Pharma, Pakistan) is an antifibrotic drug being tested for its potential role in treating oral submucous fibrosis (OSF). This intervention will be administered orally at a dose of 200 mg, twice daily for a specified treatment period which will be 6 months for Group 3 .

    Pirfenidone modulates fibrotic pathways by inhibiting TGF-β and collagen synthesis, reducing fibrosis progression.

    Distinction from Other Arms: Unlike Metformin, which has antifibrotic effects via AMPK activation, Pirfenidone specifically targets profibrotic cytokines. The Control Group will receive either a supportive care for OSF

  • Beclomaethasone and Vitamin EDrug

    Also called Beclamethasone, Vitamin E

    The Supportive Care Group will receive Beclomethasone mouthwash (three times daily) and Vitamin E 400 mg (once daily) as part of supportive care for oral submucous fibrosis . This intervention serves as a comparison group to evaluate the efficacy of Metformin and Pirfenidone.

    Beclomethasone is a topical corticosteroid that reduces inflammation and provides symptomatic relief in OSF.

    Vitamin E is an antioxidant that may help reduce oxidative stress and improve tissue healing.

    Distinction from Other Arms:

    Unlike Pirfenidone and Metformin, which target fibrosis at the molecular level, Beclomethasone + Vitamin E primarily focus on symptom relief.

    This arm will serve as an active comparator to determine whether the antifibrotic effects of Metformin and Pirfenidone provide superior therapeutic benefits.

Study groups in NCT06871904
Study groupRoleWhat they receive
Beclomaethasone and Vitamin EActive comparatorGroup 1 Control (Supportive Care): Beclomethasone mouthwash three times + Capsule vitamin E 400mg daily.
Receives: Drug: Beclomaethasone and Vitamin E
Metformin + Supportive CareExperimentalGroup 2 (Metformin + Supportive Care): Metformin: 500 mg twice daily + Beclomethasone mouthwash three times + Capsule vitamin E 400mg daily.
Receives: Drug: Metformin Hydrochloride 500Mg Tablet; Drug: Beclomaethasone and Vitamin E
Pirfenidone + Supportive CareExperimentalGroup 3 (Pirfenidone + Supportive Care): Pirfenidone: 200 mg twice daily + Beclomethasone mouthwash three times + Capsule vitamin E 400mg daily.
Receives: Drug: Pirfenidone (PFD); Drug: Beclomaethasone and Vitamin E

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Exosome Secretion and Characterization in OSF Cell Lines

    This outcome evaluates the effect of Metformin and Pirfenidone on exosome secretion and size distribution in OSF cell lines. Exosomes will be isolated and characterized using Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS) to assess morphological changes, size, and concentration differences across treatment groups.

    Measured: 24, 48, and 72 hours post-treatment

  2. Changes in Fibrosis-Related Gene Expression in OSF Cell Lines

    This outcome assesses the effect of Metformin and Pirfenidone on fibrosis-related gene expression (TGF-β, Collagen 1A1, α-SMA) in OSF cell lines. Changes will be analyzed using quantitative PCR (qPCR).

    Measured: 24 and 48 hours post-treatment

  3. Reduction in Fibrosis Severity in OSF Patients

    This outcome measures clinical improvement in Oral Submucous Fibrosis (OSF) patients treated with Metformin, Pirfenidone, or Supportive Care (Beclomethasone + Vitamin E). Severity will be assessed using the Burning Mouth Index by verbal numeric rating scale (0-10) at baseline and every 4 weeks during the trial and Interincisal Mouth Opening (IMO).

    Measured: Baseline, 4 weeks, 8 weeks, and 12 weeks, 16 weeks, 20 weeks and 24 weeks

  4. Change in TGF-β and Collagen Levels in Exosomes from OSF Cell Lines

    This outcome assesses whether Metformin and Pirfenidone reduce fibrosis-related molecular markers (TGF-β and Collagen) in exosomes isolated from OSF cell lines. Exosomal protein levels will be analyzed using Western Blot and Liquid Chromatography-Mass Spectrometry (LCMS) to determine drug-induced changes in fibrosis-related pathways.

    Measured: 24, 48, and 72 hours post-treatment

Secondary outcomes (4)

  1. Morphological Changes in OSF Cell Lines Post-Treatment

    This outcome evaluates the morphological alterations in OSF cell lines following treatment with Metformin and Pirfenidone. Changes in cell shape, size, and fibrosis-associated structural modifications will be assessed using Scanning Electron Microscopy (SEM).

    Measured: 24, 48, and 72 hours post-treatment

  2. Size and Distribution of Exosomes in OSF Cell Lines

    This outcome measures changes in exosome size, distribution, and concentration after treatment with Metformin and Pirfenidone. Characterization will be performed using Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM).

    Measured: 24, 48, and 72 hours post-treatment

  3. Functional Impact of Treated OSF cells

    This outcome evaluates whether Metformin- and Pirfenidone-treated OSF cell lines, as compared to control untreated OSF cells, influence fibroblast migration and proliferation. Cell behavior will be assessed through Scratch migration and proliferation assays to determine functional effects.

    Measured: 24, 48, 72 and 96 hours post- treatment

  4. Safety and Viability of OSF Cell Lines Post-Treatment

    This outcome measures the cytotoxicity and cell viability of OSF cell lines following treatment with Metformin and Pirfenidone. MTT assay will be used to assess potential toxic effects of the drugs at different concentrations.

    Measured: 24, 48, and 72 hours post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2025
  2. Study start7 Apr 2025
  3. Primary completion30 Dec 2025
  4. Study completion30 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Clinical Trial :All groups will undergo a 24-week intervention phase. The groups will be divided according to the treatment regime. Group 1 Control (Supportive Care): Beclomethasone mouthwash three times + Capsule vitamin E 400mg daily. Group 2 (Metformin + Supportive Care): Metformin: 500 mg twice daily + Beclomethasone mouthwash three times + Capsule vitamin E 400mg daily. Group 3 (Pirfenidone + Supportive Care): Pirfenidone: twice 200 mg daily + Beclomethasone mouthwash three times + Capsule vitamin E 400mg daily. Each group will be advised to refrain from spicy ingredients and cease eating pan, chalia or gutkha. All groups will be instructed to perform a mouth-opening stick exercise twice daily, alternating sides, holding the stick for 10 minutes on each side, with a 10-minute rest in between.Clinical evaluations will be conducted every 4 weeks
Masking
Single blind
Who is masked
Participant
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06871904
Sponsor's protocol ID
9840125ARMM
Other IDs
Ethical Review Committee
Acronym
"FIBR-MET-PF"
Status last verified
Jan 2026
First submitted
5 Mar 2025
Last updated
3 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: IPD will not be shared because this study involves in vitro experiments on OSF cell lines and does not include individual patient data. Additionally, for the clinical trial component, data privacy regulations and ethical considerations prevent the sharing of participant-specific data

Publications

  • Wang L, Zhong NN, Wang X, Peng B, Chen Z, Wei L, Li B, Li Y, Cheng Y. Metformin Attenuates TGF-beta1-Induced Fibrosis in Salivary Gland: A Preliminary Study. Int J Mol Sci. 2023 Nov 13;24(22):16260. doi: 10.3390/ijms242216260.

    PubMed 38003450

  • Huh JY, Lee JH, Song JW. Efficacy and safety of combination therapy with pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis. Front Pharmacol. 2023 Dec 12;14:1301923. doi: 10.3389/fphar.2023.1301923. eCollection 2023.

    PubMed 38192410

  • Chen X, Xie H, Guo J. Drug treatment for oral submucous fibrosis: an update. BMC Oral Health. 2023 Oct 12;23(1):748. doi: 10.1186/s12903-023-03488-9.

    PubMed 37828490

  • Ahmadpour F, Rasouli HR, Talebi S, Golchin D, Esmailinejad MR, Razie A. Effects of exosomes derived from fibroblast cells on skin wound healing in Wistar rats. Burns. 2023 Sep;49(6):1372-1381. doi: 10.1016/j.burns.2023.02.003. Epub 2023 Feb 14.

    PubMed 36828692

  • Abbasi-Malati Z, Azizi SG, Milani SZ, Serej ZA, Mardi N, Amiri Z, Sanaat Z, Rahbarghazi R. Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look. Cell Commun Signal. 2024 Feb 15;22(1):130. doi: 10.1186/s12964-024-01510-3.

    PubMed 38360641

  • Abbasi R, Nejati V, Rezaie J. Exosomes biogenesis was increased in metformin-treated human ovary cancer cells; possibly to mediate resistance. Cancer Cell Int. 2024 Apr 16;24(1):137. doi: 10.1186/s12935-024-03312-6.

    PubMed 38627767

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Metformin Hydrochloride 500Mg Tablet, Pirfenidone (PFD) and Beclomaethasone and Vitamin E in people with Oral Submucous Fibrosis, run by Ziauddin University at 1 site in Pakistan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Exosome Secretion and Characterization in OSF Cell Lines (time frame: 24, 48, and 72 hours post-treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06871904, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2026.

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