Conditions: Oral Leukoplakia
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 52
Healthy volunteers: no

Brief summary:
The goal of this clinical research study is to learn how Actos (pioglitazone) may affect oral premalignant lesions (OPLs) and/or the risk of mouth cancer. The safety of this drug will also be studied.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine the clinical and histologic response of oral premalignant lesions to 24 weeks of therapy with pioglitazone, 45 mg once daily (qd), defined as 50% or greater reduction in the sum of all measured products of perpendicular dimensions of target lesions, or improvement in the degree of dysplasia or hyperplasia.

SECONDARY OBJECTIVES:

I. To determine the degree of change of putative biomarkers of pioglitazone efficacy including (but not restricted to) and in order of priority, tissue levels of:

* PPAR gamma,
* cyclin D1 and p21 as indirect measures of pharmacological effect
* TUNEL for apoptosis and Ki-67 for proliferation
* transglutaminase and involucrin as markers of squamous differentiation
* 15-PGDH, loss of heterozygosity (LOH). II. To determine the degree of change of C-reactive protein (CRP) in plasma. III. To assess tobacco and alcohol use among trial participants and to examine the relationship of tobacco and alcohol use to treatment response.

IV. To assess the safety of this agent in this population.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive pioglitazone hydrochloride orally (PO) once daily (QD) for 24 weeks.

ARM II: Patients receive placebo PO QD for 24 weeks.

After completion of study treatment, patients are followed up for 2 weeks.

Arms:
arm 1: Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks arm 2: Three (3) placebo capsules by mouth once daily for 24 weeks

Interventions: intervention 1: Pioglitazone hydrochloride intervention 2: placebo intervention 3: laboratory biomarker analysis
Intervention descriptions: intervention 1: Three (3) pioglitazone 15 mg capsules by mouth once daily for 24 weeks (+/- 1 week) intervention 2: Three (3) pioglitazone placebo capsules by mouth once daily for 24 weeks (+/- 1 week) intervention 3: Correlative studies

Protocol document: