Recruiting
Phase 2

Pioglitazone & Metformin

Sponsor:

University of Minnesota

Code:

NCT05727761

Conditions

Oral Leukoplakia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

pioglitazone-metformin

Study Details

Brief summary:

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.

Conditions

Oral Leukoplakia

Study ID

NCT05727761

Start date

Jan 1, 2025

Status verified date

Jul, 2026

Completion date

Jul 30, 2027

Anticipated

Primary completion date

Jul 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

36 participants

Anticipated

Intervention Model

Single group

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: oral leukoplakia patients

36 total high risk oral leukoplakia patients.

Interventions

pioglitazone-metformin

Treatment with pioglitazone-metformin (15mg/500mg) twice a day for 12 weeks

Primary outcome measure

  • Clinical change in leukoplakia [ Time Frame: after 12 weeks of intervention or at early termination. ]
  • histologic change in leukoplakia [ Time Frame: after 12 weeks of intervention or at early termination. ]
  • Change in Ki-67 [ Time Frame: After 12 weeks of intervention or at early termination ]

Central Contacts and Locations

Central contacts

Beverly Wuertz

612-625-3090knier003@umn.edu

Locations

University of Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55455

Contacts

Beverly Wuertz

612-625-3090knier003@umn.edu

HealthPartners

Recruiting

Saint Paul, Minnesota, United States, 55130

Contacts

Kirsten Dalrymple

651-254-5316Kirsten.A.Dalrymple@healthpartners.com

More Information

Sponsor

University of Minnesota

Last update posted

Jul 29, 2026

Last verified

Jul, 2026

Keywords

  • oral leukoplakia
  • oral cancer prevention
  • pioglitazone
  • metformin
  • precancerous oral lesion

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Minnesota on 2026-07-29.