Role of Pioglitazone Therapy in Management of Insulin Resistance Associated With Androgen Deprivation Therapy (ADT) in Patients With Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- HOMA-IR
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male, age ≥18 years of age.
- •Body Mass Index of > 25 kg/m2
- •Biopsy-confirmed prostate adenocarcinoma currently on androgen deprivation therapy (ADT) for minimum of 3 months for the ADT group and biopsy-confirmed prostate adenocarcinoma not on ADT for control group
- •Hemoglobin > 11 g/dL, Creatinine < 1.5x ULN and liver function tests < 2x ULN
- •Participant must be able to read, write, and understand the English language and be able to provide written consent
- •Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
排除标准
- •Known clinically significant severe COPD, ischemic heart disease, congestive heart failure, and/or significant cardiac arrhythmias
- •Any patient with known diabetes (A1c > 6.4%) or an anti-diabetic drug
- •Any condition contraindicating additional blood collection beyond standard of care
- •Subjects with known allergy to lidocaine (this is used to anesthetize area for fat biopsy)
- •Subjects with known allergy to pioglitazone or other thiazolidinediones
- •Subjects with pioglitazone use in last 6 months
- •Subjects with congestive Heart Failure Class 3 or 4
- •Subjects with osteoporosis, including history of fragility fracture
- •Subjects with history of bladder cancer
- •Subjects on chronic use of androgens, or opiates in the last 6 months or with panhypopituitarism, congenital HH (hypogonadotropic hypogonadism), prolactinoma, head trauma
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to undergo study procedures.
研究组 & 干预措施
Prostate cancer on ADT receiving pioglitazone
Subjects will receive a 12-week supply of pioglitazone 30 mg dose 1 tab daily
干预措施: Pioglitazone 30 mg (Drug)
Prostate cancer on ADT receiving placebo
Subjects will receive a 12 week supply of placebo pills containing cellulose
干预措施: Placebo (Drug)
结局指标
主要结局
HOMA-IR
时间窗: 12 weeks
Change in HOMA-IR (the main index for evaluating insulin resistance) following pioglitazone and placebo treatment.
次要结局
- IRβ(12 weeks)
- JNK-1(12 weeks)
- IRS-1 serine phosphorylation(12 weeks)
- IRS-1(12 weeks)
- IKK-β(12 weeks)
- PTB-1B(12 weeks)
- SOCS-3(12 weeks)
- TLR-4(12 weeks)
- AKT-2(12 weeks)
- GLUT-4(12 weeks)
- TNF-α(12 weeks)
- IL 1β(12 weeks)
研究者
paresh Dandona
SUNY Distinguished Professor of Medicine
State University of New York at Buffalo