Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06332612
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-27
First Post:
2024-02-22
Brief Title:
Metformin Repurposing in Oral Submucous Fibrosis Unveiling In Vitro Signaling Pathways Progressing to Clinical Trial
Sponsor:
Ziauddin University
Organization:
Ziauddin University
Study Overview
Official Title:
Repurposing Metformin for the Treatment of Oral Submucous Fibrosis Unraveling Novel Signaling Pathways In Vitro and Advancing to Clinical Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MROSF
Brief Summary:
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
Detailed Description:
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 83105 to 162105 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 913
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 Smad23 Additionally metformin inhibits Smad23 phosphorylation independently and activates AMPK hindering Smad3 phosphorylation The impact on reactive oxygen species ROS generation moderates TGF-β1-induced Smad23 phosphorylation and myofibroblast differentiationMetformin 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 therapys impact on postmenopausal ovaries patients with type 2 diabetes mellitus T2DM exhibited isotropic collagen organization and reduced fibrosis during oophorectomyThe 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
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 Smad23 Additionally metformin inhibits Smad23 phosphorylation independently and activates AMPK hindering Smad3 phosphorylation The impact on reactive oxygen species ROS generation moderates TGF-β1-induced Smad23 phosphorylation and myofibroblast differentiationMetformin 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 therapys impact on postmenopausal ovaries patients with type 2 diabetes mellitus T2DM exhibited isotropic collagen organization and reduced fibrosis during oophorectomyThe 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None