Oral LeukoplakiaPhase 2NCT05727761
Pioglitazone-Metformin Combination Treatment for High Risk Oral Preneoplasia
A Phase 2 study testing pioglitazone-metformin in people with Oral Leukoplakia, run by University of Minnesota at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oral Leukoplakia
- What is being tested?
- pioglitazone-metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2025to 30 Jul 2027
- Phase
- Phase 2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55455
Beverly Wuertz, 612-625-3090, knier003@umn.edu
- Recruiting
HealthPartners
Saint Paul, Minnesota, 55130
Kirsten Dalrymple, 651-254-5316, Kirsten.A.Dalrymple@healthpartners.com
About this study
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
- Being tested
- pioglitazone-metformin
- Keywords
- oral leukoplakia, oral cancer prevention, pioglitazone, metformin, precancerous oral lesion
- Medical subject headings
- Leukoplakia, Oral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pioglitazone-metforminDrug
Treatment with pioglitazone-metformin (15mg/500mg) twice a day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| oral leukoplakia patients | Experimental | 36 total high risk oral leukoplakia patients. Receives: Drug: pioglitazone-metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical change in leukoplakia
a partial or complete clinical response defined as 50% or greater reduction in the sum of measured targeted lesions
Measured: after 12 weeks of intervention or at early termination.
histologic change in leukoplakia
reduction of the leukoplakia grade in > 50% of treated participants
Measured: after 12 weeks of intervention or at early termination.
Change in Ki-67
Ki-67 proliferative indices in lesions
Measured: After 12 weeks of intervention or at early termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2023
- Study start1 Jan 2025
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Oral LeukoplakiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Treatment with pioglitazone-metformin (15mg/500mg) twice a day for 12 weeks in 36 total high risk oral leukoplakia patients.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frank Ondrey, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05727761
- Sponsor's protocol ID
- ENT-2022-31139
- Status last verified
- Jul 2026
- First submitted
- 19 Jan 2023
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Gates JC, Abouyared M, Shnayder Y, Farwell DG, Day A, Alawi F, Moore M, Holcomb AJ, Birkeland A, Epstein J. Clinical Management Update of Oral Leukoplakia: A Review From the American Head and Neck Society Cancer Prevention Service. Head Neck. 2025 Feb;47(2):733-741. doi: 10.1002/hed.28013. Epub 2024 Nov 25.
PubMed 39584361Puri A, Wuertz B, Rhodus NL, Ondrey FG. Safety of oral mucosal punch biopsy and other oral biospecimen collections in clinical research. Oral Surg Oral Med Oral Pathol Oral Radiol. 2025 Mar;139(3):344-351. doi: 10.1016/j.oooo.2024.10.084. Epub 2024 Oct 30.
PubMed 39532605