An Endometrial Cancer Chemoprevention Study of Metformin Versus No Treatment in Women With a Body Mass Index (BMI) >/= 30 kg.m2 and Hyperinsulinemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- To Evaluate the Participant Body Weight in Pounds (Lbs)
研究概览
简要总结
The goal of this clinical research study is to learn about the effects of metformin and/or a program called "lifestyle intervention" on the endometrium (inner lining of the uterus) in post-menopausal women who are also obese (both are risk factors for endometrial cancer). Researchers also want to learn how insulin levels will be affected by metformin, diet and/or exercise.
Metformin is designed to treat both diabetes and insulin resistance. Insulin resistance is a condition in which the body makes insulin but does not use it properly. It is often referred to as "pre-diabetes". Many people with insulin resistance have high levels of both sugar and insulin in their blood at the same time, which have been reported in patients with endometrial cancer.
In this study, metformin will be compared to a placebo. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.
Lifestyle intervention is made up of a series of in-person sessions where you meet with a coach to discuss strategies for losing weight and ways to increase physical activity. It also consists of materials designed to help you lose weight and will offer opportunities for supervised exercise.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to 1 of 4 study groups:
- Metformin only.
- Placebo and lifestyle intervention.
- Metformin and lifestyle intervention.
- Placebo only.
Neither you nor the study staff will know if you are receiving metformin or placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving.
In the first month you will gradually increase the dose of metformin/placebo by mouth as listed below:
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •For this study, only women will be enrolled.
- •Body Mass Index (BMI) > or = 30 kg/m2
- •Not frankly diabetic, as measured by a fasting blood glucose </=126 mg/dL.
- •Demonstrate hyperinsulinemia with a QUICK I value </= 0.
- •Age >/= 50 and </= 65
- •Zubrod Performance Scale 0-1
- •Hemoglobin >/= 10 g/dl
- •TSH 0.27 - 4.20 µlU/mL
- •Menopause as defined as no menses for 1 year and/or FSH >/= 25.8 mIU/ml
- •Must be able to read, write, and speak English.
- •Must have a Primary Care Provider (PCP).
排除标准
- •Prior hysterectomy or endometrial ablation
- •ALT >/r = 2.0x Upper Limit of Normal (ULN)
- •Serum creatinine > /= 1.4 mg/dl
- •Triglycerides (fasting) >/ = 400
- •Known inability to participate in the ongoing appointments for the four months of the study and scheduled follow-up tests.
- •Significant medical or psychiatric history which would make the participant a poor protocol candidate, in the opinion of the principal investigator, for any aspect of study participation including metformin, unsupervised exercise program or dietary behavior change.
- •Participant reported history of congestive heart failure
- •Prior treatment with Metformin
- •Currently being treated for diabetes or meeting criteria for new diagnosis of diabetes.
- •Known allergy to Metformin or other biguanide (Proguanil).
- •Use of Aromatase Inhibitors, GNRH-agonists i.e.Lupron, Zoladex within the last 6 months
- •Use of SERMS (selective estrogen receptor modulators) in the past 6 months, including Tamoxifen and Raloxifene
- •Hormone replacement therapy within the last 6 months
- •Women who have been treated with chemotherapy for prior malignant disease or currently have an untreated malignancy other than non-melanoma skin cancer
- •Patients who have had prior radiation to the pelvis
研究组 & 干预措施
Metformin
Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
干预措施: Metformin (Drug)
Metformin
Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
干预措施: Endometrial Biopsy (Procedure)
Metformin
Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
干预措施: Questionnaires (Behavioral)
Placebo + Lifestyle Intervention
Placebo taken by mouth twice daily for 4, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
干预措施: Placebo (Other)
Placebo + Lifestyle Intervention
Placebo taken by mouth twice daily for 4, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
干预措施: Endometrial Biopsy (Procedure)
Placebo + Lifestyle Intervention
Placebo taken by mouth twice daily for 4, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
干预措施: Lifestyle Intervention (Behavioral)
Placebo + Lifestyle Intervention
Placebo taken by mouth twice daily for 4, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
干预措施: Questionnaires (Behavioral)
Metformin + Lifestyle Intervention
Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
干预措施: Metformin (Drug)
Metformin + Lifestyle Intervention
Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
干预措施: Endometrial Biopsy (Procedure)
Metformin + Lifestyle Intervention
Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
干预措施: Lifestyle Intervention (Behavioral)
Metformin + Lifestyle Intervention
Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
干预措施: Questionnaires (Behavioral)
Placebo
Placebo taken by mouth twice daily for 4, 30 day cycles.
干预措施: Placebo (Other)
Placebo
Placebo taken by mouth twice daily for 4, 30 day cycles.
干预措施: Endometrial Biopsy (Procedure)
Placebo
Placebo taken by mouth twice daily for 4, 30 day cycles.
干预措施: Questionnaires (Behavioral)
结局指标
主要结局
To Evaluate the Participant Body Weight in Pounds (Lbs)
时间窗: Visit 2 (1 week), 4 months, and 1 year
This study will use a 2 x 2 randomized design with all 100 post- menopausal subjects being randomized to metformin, placebo, placebo and intensive lifestyle intervention, or metformin and intensive lifestyle intervention. Treatments will last 4 months. Participants will be assessed at baseline and end of treatment with endometrial sampling to see if there are changes in the biomarkers.
To Evaluate the Percentage of Ki-67 Positive Cells
时间窗: Visit 2 (1 week), 4 months, and 1 year
The Q-PCR analyses will be performed in the Quantitative Genomics Core Facility at the University of Texas Medical School at Houston. Over the last 3 years we have used several techniques including differential display, microchip array screening, and real-time quantitative PCR to find such genes. The tools we have developed are directly applicable to the investigation of surrogate endpoint biomarkers (SEBs). Identification of appropriate biomarkers is essential for this study.
次要结局
- Weight Loss(Visit 2 (1 week), 4 months, and 1 year)
- BMI(Visit 2 (1 week), 4 months, and 1 year)