Insulin Resistance Following Androgen Deprivation Therapy in Men With Prostate Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Insulin Sensitivity
研究概览
简要总结
Prostate cancer is the most common cancer in men in the United States. Suppression of male hormone levels by using GnRH agonist ("hormone blocking therapy") for a few years is routinely used to treat prostate cancer. While the treatment is very effective, it decreases muscle mass and increases fat mass. This results in a decrease in insulin action (also called insulin resistance) and increases the likelihood of diabetes. It may also contribute to risk of developing heart disease. The investigators propose to conduct a trial that will:-
- study the mechanisms through which GnRH agonists cause insulin resistance.
- Evaluate a treatment that can decrease insulin resistance. This is a randomized, placebo controlled, double-blind trial. Forty-four men with prostate cancer will be recruited in the trial before starting GnRH agonist therapy. Participants will undergo metabolic studies to evaluate insulin action (called insulin clamp), abdominal fat tissue biopsy to study insulin action at the cellular level and blood draws. The study volunteers will then be given either a placebo tablet or pioglitazone tablet to take once a day for the next six months. The metabolic tests, blood test and fat tissue biopsy will be obtained again at the end of the study.
详细描述
STUDY PLAN The Study will be conducted at Saint Louis University. The investigators plan to conduct a prospective, randomized, double-blind, placebo-controlled trial in 44 men with nonmetastatic prostate cancer who will receive ADT with long acting GnRH agonist. Patients will be recruited from clinical practice of division of Urology. The patients that are planning to undergo ADT as part of standard of care treatment for their prostate cancer will be offered a choice of enrolling in the study prior to initiating ADT.
Study subjects will undergo EHC, subcutaneous fat biopsy and have a blood sample drawn prior to starting ADT. The subjects 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 EHC, fat biopsy and blood sampling and will be discharged from the study. Study visits will be conducted at clinical research center of division of Endocrinology at Salus Center.
Screening:
All subjects will complete the following procedures prior to participating in the study:-
- Medical History. Subjects who are on insulin or sulfonylureas for diabetes will be advised that pioglitazone use may lead to low blood sugars. Subjects with congestive heart failure will be advised of the possibility that their edema or shortness of breath may worsen.
- Physical Exam
- Informed consent
- Lab test: CBC and comprehensive metabolic panel (CMP) if not available in medical records from last 3 months
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Men between the ages of 18-85 years
- •Prostate cancer, non-metastatic
- •Planning to initiate ADT with long acting GnRH agonist
排除标准
- •Prior history of ADT use
- •Used pioglitazone in last 6 months
- •Congestive Heart Failure Class 3 or 4
- •Osteoporosis, including history of fragility fracture
- •history of bladder cancer
- •Hemoglobin <8 g/dl
- •eGFR <15 ml/min/1.73m2
- •liver enzymes (ALT or AST) >3 times the upper limit of normal
研究组 & 干预措施
Pioglitazone Arm
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.
干预措施: Pioglitazone 30 Mg Oral Tablet (Drug)
Placebo Arm
Subjects will self-administer an oral placebo tablet containing cellulose daily for 6 months.
干预措施: Pioglitazone placebo tablet (Drug)
结局指标
主要结局
Insulin Sensitivity
时间窗: 6 months
The primary endpoint of the study is to detect a difference in insulin sensitivity as measured by whole body glucose uptake during EHC after treatment with pioglitazone as compared to placebo.
次要结局
- HOMA-IR(6 months)
- Insulin signaling(6 months)
- C Reactive Protein(6 months)
研究者
Sameer Siddiqui, MD FACS
C. Rollins Hanlon Endowed Chair of Surgery
St. Louis University