Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Nutritional and Metabolic Diseases

Prostatic Neoplasms

Insulin Resistance

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Hyperinsulinism

Metabolic Diseases

Glucose Metabolism Disorders

All Drugs and Chemicals

Hypoglycemic Agents

Lipid Regulating Agents

Androgens

Insulin

Insulin, Globin Zinc

Pioglitazone

Gemfibrozil

Subjects will self-administer a 30 mg pioglitazone oral tablet daily for 6 months.

For patient taking a diabetic regimen of gemfibrozil, the dose will be 15 mg daily.

Pioglitazone 30 mg

Subjects will self-administer an oral placebo tablet containing cellulose daily for 6 months.

placebo tablet

Prostate cancer is the most common malignancy amongst men in United States. Androgen deprivation therapy (ADT) with long acting gonadotropin releasing hormone agonists is routinely used as adjuvant therapy in intermediate and high risk localized or locally advanced prostate cancer. Since ADT induces insulin resistance and diabetes, it is important that cellular and molecular effects of ADT are investigated to define precisely the mechanisms involved in the pathogenesis of insulin resistance. Pioglitazone, a known insulin sensitizer, may provide amelioration of insulin resistance in these patients.

Investigators plan to conduct a prospective, randomized, double-blind, placebo-controlled trial in 44 men with nonmetastatic prostate cancer who are receiving ADT with long acting GnRH agonist (study group). Study subjects will undergo insulin clamp, subcutaneous fat biopsy, muscle biopsy, have a blood sample taken and fibroscan performed prior to randomization of study drug. They will then be randomized to 30 mg pioglitazone or placebo tablet daily for 6 months. Blood samples will be drawn 2 and 4 months following the initiation of the study drug. The final study visit will be at 6 months. Subjects will undergo clamp, fat biopsy, muscle biopsy, blood sampling, fibroscan and will be discharged from the study.

Insulin Resistance and Androgen Deprivation Therapy

Insulin Resistance in Men With Prostate Cancer on Androgen Deprivation Therapy

The primary endpoint of the study is to detect a difference in insulin sensitivity as measured by whole body glucose uptake during clamps after treatment with pioglitazone as compared to placebo.

A secondary endpoint for the study will be comparison of the relative change from baseline in insulin signaling after pioglitazone or placebo.

St. Louis University

Professor of Medicine

Gland and Hormone Related Diseases

Diabetes Mellitus, Type 2

Diabetes Mellitus

Endocrine System Diseases

Subjects will receive a 12-week supply of pioglitazone 30 mg dose 1 tab daily

Subjects will receive a 12 week supply of placebo pills containing cellulose

No intervention will be done in this group

pioglitazone 30 mg dose 1 tab daily will be given for 12 weeks

placebo pills containing cellulose 1 pill daily will be given for 12 weeks

Placebo

Paresh Dandona, MD, PhD

This study is being done to establish the mechanisms underlying insulin resistance (reduced insulin action that can lead to high blood sugar and maybe diabetes) in patients undergoing androgen deprivation therapy (ADT) for prostate carcinoma as well as to investigate the role of pioglitazone therapy in reduction/ reversal of that insulin resistance

This is a single-center, cross-sectional then prospective, randomized single-blinded study with 2 groups of subjects. One group will be men with prostate cancer in various stages of ADT and the other group will be men with prostate cancer not on ADT as control group.

Patients interested in participating who meet the inclusion/exclusion criteria and who agree to undergo blood draws and fat biopsy will be identified from the Genito-urinary oncology and urology clinics. These patients will be referred to the Diabetes and Endocrinology Research Center of WNY where they will undergo blood draws in fasting state.

On the screening day, participants will be asked to complete the informed consent, medical history and physical exam, and non-fasting blood draws (for CBC, CMP and HbA1c) prior to participating in the study. 30 ml of blood will be drawn at this visit.

Subjects who qualify and consent to take part in the study will be called in for the baseline study visit where they will undergo blood draws in fasting state. HOMA-IR method will be used to determine insulin resistance. Subcutaneous fat biopsies will be performed in all patients.

Within the ADT group, subjects will be assigned a number by a computerized simple random number generation program (Excel, Microsoft Inc.) and will be randomized (1:1) to receive either pioglitazone or placebo. The patient will be blinded to the treatment, however, the research team will not. Subjects will be given a 12 week supply of pioglitazone 30 mg or placebo pills containing cellulose that will take once a day in morning. Subjects who develop side effects (weight gain, pedal edema) on the 30 mg dose will be asked to reduce the dose to 15 mg.

Subjects will then return to the research center in 12 weeks for visit 2 where the fasting blood draws and subcutaneous fat biopsies will be performed again. The subjects will then be discharged from the study and follow with their physicians. Subject will receive a phone call after 1 and 4 weeks following start of treatment to collect any safety data. Patients will be instructed to call the research center anytime they have a question or side effects.

Pioglitazone and Insulin Resistance in ADT

Role of Pioglitazone Therapy in Management of Insulin Resistance Associated With Androgen Deprivation Therapy (ADT) in Patients With Prostate Cancer

Change in HOMA-IR (the main index for evaluating insulin resistance) following pioglitazone and placebo treatment.

Determine levels of IRS-1 serine phosphorylation in adipose tissue and MNC as a molecular marker of inflammation induced insulin resistance at baseline and after pioglitazone and placebo treatments

Changes in expression of insulin signaling gene (IRβ) in both adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of insulin signaling gene (IRS-1) in both adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of insulin signaling gene (AKT-2) in both adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of GLUT-4 in adipose tissue between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of proinflammatory gene (TNF-α) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of proinflammatory gene (IL 1β) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of proinflammatory gene (IKK-β) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of proinflammatory gene (SOCS-3) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of proinflammatory gene (PTB-1B) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of proinflammatory gene (JNK-1) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Changes in expression of proinflammatory gene (TLR-4) that interfere with insulin signaling transduction in adipose tissue and MNC between the ADT and non-ADT groups at baseline and after pioglitazone and placebo treatments in ADT group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Insulin Resistance and Androgen Deprivation Therapy	NCT04995978	Prostate Cancer Insulin Resista...	Pioglitazone 30... placebo tablet	18 Years - 85 Years	St. Louis University
Pioglitazone and Insulin Resistance in ADT	NCT05098327	Prostate Cancer Insulin Resista... Diabetes Mellit... Androgen Defici...	Pioglitazone 30... Placebo	18 Years -	State University of New York at Buffalo

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