Pioglitazone-Metformin Combination Treatment for High Risk Oral Preneoplasia

December 22, 2025 updated by: University of Minnesota
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota
        • Contact:
      • Saint Paul, Minnesota, United States, 55130

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Biopsy proven hyperplasia in high risk anatomic areas (floor of mouth, mobile tongue, oropharynx). Hyperplasia or dysplasia of any grade in any erythroplakia lesion. Mild, moderate or severe dysplasia within the lesion at any site of the oral cavity or oropharynx.
  • Must have objective evidence of oral leukoplakia that is measurable in 2 dimensions per RECIST. The lesion(s) may be clinically characterized by leukoplakia, erythroplakia, erythro/leukoplakia. Lesions may be located in the oral cavity or oropharynx. However, the index lesion must be located in an anatomic site accessible by punch biopsy and be a minimum of 4mm x 8 mm to permit a 4mm punch biopsy.
  • Age 18 years or older at the time of consent.
  • Evidence of adequate organ function within 14 days prior to Day 1
  • Able to comply with treatment (i.e. able to swallow a tablet whole, not crushed) and complete a 12 week course of twice daily medication as required by this study in the opinion of the treating investigator.
  • Body mass index (BMI) is ≥ 18.5.
  • Sexually active persons of child-bearing potential agrees to use adequate contraception (a hormonal method that has been in continual use for a minimum of 3 months prior to the study screening visit, a barrier method, or abstinence) for the duration of study participation.
  • Provides voluntary written consent prior to the performance of any research related activity.

Exclusion Criteria:

  • Pregnant or breastfeeding or planning to become pregnant.
  • A concurrent diagnosis of Type I or Type II diabetes that is being treated with insulin or an antidiabetic agent. Participants whose Type II diabetes is controlled with diet and/or exercise alone are eligible provided they meet all other eligibility criteria.
  • Participant is taking another investigational agent (not approved by the FDA for any indication).
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ACTOplus Met, pioglitazone or metformin.
  • Any contraindication to biopsy - this study requires a 4 mm punch biopsy of a lesion and of nearby normal tissue prior to treatment and at the end of the 12 week treatment period.
  • History of bladder cancer, including in situ bladder cancer.
  • History of invasive cancer (other than non-melanoma skin cancer or cervical cancer in situ) active within 18 months prior to the baseline study visit. (Participants who have a history of cancer that was curatively treated without evidence of recurrence in the 18 months prior to the baseline study visit are considered eligible).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: oral leukoplakia patients
36 total high risk oral leukoplakia patients.
Drug: pioglitazone-metformin
Treatment with pioglitazone-metformin (15mg/500mg) twice a day for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical change in leukoplakia
Time Frame: after 12 weeks of intervention or at early termination.
a partial or complete clinical response defined as 50% or greater reduction in the sum of measured targeted lesions
after 12 weeks of intervention or at early termination.
histologic change in leukoplakia
Time Frame: after 12 weeks of intervention or at early termination.
reduction of the leukoplakia grade in > 50% of treated participants
after 12 weeks of intervention or at early termination.
Change in Ki-67
Time Frame: After 12 weeks of intervention or at early termination
Ki-67 proliferative indices in lesions
After 12 weeks of intervention or at early termination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Investigators

  • Principal Investigator: Frank Ondrey, University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2025

Primary Completion (Estimated)

July 28, 2026

Study Completion (Estimated)

July 28, 2026

Study Registration Dates

First Submitted

January 19, 2023

First Submitted That Met QC Criteria

February 4, 2023

First Posted (Actual)

February 14, 2023

Study Record Updates

Last Update Posted (Actual)

December 24, 2025

Last Update Submitted That Met QC Criteria

December 22, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ENT-2022-31139

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Oral Leukoplakia

Clinical Trials on pioglitazone-metformin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lithuania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe