NCT05727761

Pioglitazone-Metformin Combination Treatment for High Risk Oral Preneoplasia

Recruiting now Phase 2 Last updated 24 December 2025

What this trial tests

Phase 2 trial testing pioglitazone-metformin in Oral Leukoplakia in 36 participants. Currently enrolling.

Timeline

1 January 2025

Primary endpoint
28 July 2026

28 July 2026

Quick facts

Lead sponsor	University of Minnesota
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	36
Start date	1 January 2025
Primary completion	28 July 2026
Estimated completion	28 July 2026
Sites	2 locations across United States

Drugs / interventions tested

• pioglitazone-metformin

Conditions studied

• Oral Leukoplakia — all drugs for Oral Leukoplakia →

Sponsor

University of Minnesota

Who can join

18 and older, any sex, with Oral Leukoplakia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This is a Phase IIa oral cavity leukoplakia study of pioglitazone 15mg and metformin 500mg BID for 12 weeks. The primary objective is to determine the clinical and histologic changes of leukoplakia from baseline following a 12 week course of twice daily pioglitazone-metformin. Outcomes are defined as are a reduction of the leukoplakia grade in \> 50% of treated participants and a partial or complete clinical response defined as 50% or greater reduction in the sum of measured targeted lesions. In addition, participants who show clinical and histologic improvement should correlate with a significant reduction of Ki-67 proliferative indices in lesions of these participants as compared to baseline.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical Management Update of Oral Leukoplakia: A Review From the American Head and Neck Society Cancer Prevention Service.
   Gates JC, Abouyared M, Shnayder Y, Farwell DG, et al · · 2025 · cited 10× · PMID 39584361 · DOI 10.1002/hed.28013
2. Promising immunomodulators for management of substance and alcohol use disorders.
   Acuña AM, Park C, Leyrer-Jackson JM, Olive MF. · · 2024 · cited 5× · PMID 38803314 · DOI 10.1080/14656566.2024.2360653
3. Chemoprevention of Head and Neck Cancer: A Review of Current Approaches and Future Perspectives.
   Han S, Bommireddy R, Kim P, Selvaraj P, et al · · 2024 · cited 3× · PMID 38978394 · DOI 10.1158/1940-6207.capr-24-0093
4. The Emerging Role of Peroxisome Proliferator-Activated Receptors in Cancer Stemness.
   Parejo-Alonso B, Mascaraque M, Royo-García A, Sancho P. · · 2025 · cited 1× · PMID 41148824 · DOI 10.3390/cells14201610
5. Analysis of nuclear receptor expression in head and neck cancer.
   Mortensen L, Koenigsberg CK, Kimbrough TG, Ping J, et al · · 2025 · cited 1× · PMID 39754894 · DOI 10.1016/j.cancergen.2024.12.003
6. Effect of metformin on hypoxia-associated gene expression in oral cavity squamous cell carcinoma in non-diabetic patients - a prospective window of opportunity study.
   Mueller SA, Elicin O, Monney B, Rau T, et al · · 2025 · PMID 40468055 · DOI 10.1007/s00405-025-09493-8
7. Safety of oral mucosal punch biopsy and other oral biospecimen collections in clinical research.
   Puri A, Wuertz B, Rhodus NL, Ondrey FG. · · 2025 · PMID 39532605 · DOI 10.1016/j.oooo.2024.10.084