Alcohol-related Breast Cancer in Postmenopausal Women - Effect of PPARG2pro12ala Polymorphism on Female Sex-hormone Levels and Interaction With Alcohol Consumption and NSAID Usage
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Serum estrone sulphate (pmol/l)
研究概览
简要总结
Postmenopausal women, stratified by a peroxisome proliferator-activated receptor gamma-2 (PPARG) polymorphism, were given the following treatments in a random order with a 5w wash-out period: a 400mg ibuprofen tablet or a placebo tablet; both treatments were followed after 30min by a single acute dose of 0.4g alcohol per kg bw. Serum estrogen levels were measured before and at three timepoints after alcohol intake. It is hypothesized that the acute decrease in estrogen sulphate and other markers of estrogens after alcohol intake is modulated by ibuprofen and by PPARG genotype.
详细描述
In a pilot human intervention trial we aimed to determine the effect of the PPARG Pro12Ala polymorphism and the PPARγ stimulator, Ibuprofen, on sex-hormone levels following alcohol intake in postmenopausal women. Seven women with PPARG Pro12Ala and 18 PPARG wildtype women were included.The study was performed as a randomised, double-blinded, placebo controlled 2x24 h crossover study. The volunteers were randomised to 1 of 2 groups who got the two treatments in different orders. Treatment 1 was a placebo tablet with water followed after 30min by an alcoholic drink providing 0,4g alcohol per kilogram bw and treatment 2 was an Ibuprofen tablet (400mg) with water followed by the same alcoholic drink. The two treatments were separated by a 5-7 weeks washout period. Alcohol was supplied as 7.7% ethanol in a lime-flavoured drink and was consumed over 15 min. EDTA-plasma was collected 40min before and 30, 60 and 90 min after ethanol intake as well as after 24 hours. Ibuprofen (400mg) was provided together with 100mL water 30min before the ethanol. Urine was collected throughout the 24 hour interval. Serum estrone, estrone sulphate, serum estrogen-binding globulin (SHBG), and ethanol were determined. It is hypothesized that the acute decrease in estrogen sulphate and other markers of estrogens after alcohol intake is modulated by ibuprofen and by PPARG genotype.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •postmenopausal (last menses at least 1 year earlier);
- •having a weekly alcohol use of less than 14 drinks
- •having a BMI of 18-35;
排除标准
- •a history of alcohol abuse
- •alcohol abstaining
- •history of hysterectomy before last menses with preservation of both ovaries (unless a medical confirmation for the postmenopausal status exists or the participant is 60 years or older);
- •major health problems, such as ulcers, heart diseases, diabetes or cancer
- •previous or current use of HRT
- •taking prescription medications that could interfere with the study (i.e. daily use of NSAIDs and/or medication that interact with PPARγ e.g. cholesterol lowering medicine);
- •being allergic to alcohol and/or Ibuprofen
研究组 & 干预措施
Sequence 1
- Ibuprofen Tab 400MG
- Placebo Tab
干预措施: Ibuprofen Tab 400 MG (Drug)
Sequence 1
- Ibuprofen Tab 400MG
- Placebo Tab
干预措施: Placebo tab (Drug)
Sequence 2
- Placebo tab
- Ibuprofen Tab 400MG
干预措施: Ibuprofen Tab 400 MG (Drug)
Sequence 2
- Placebo tab
- Ibuprofen Tab 400MG
干预措施: Placebo tab (Drug)
结局指标
主要结局
Serum estrone sulphate (pmol/l)
时间窗: from 40 min before to 90 min after alcohol consumption
Plasma estrone sulfate concentration after acute ethanol intake by Ibuprofen intake and/or PPARG genotype
次要结局
- Serum metabolomics (relative metabolite intensity)(from 40 min before to 24h after alcohol intake)
- Urine metabolomics (relative metabolite intensity)(from 40 min before to 24h after alcohol intake)
- Serum estrone (pmol/l)(from 40 min before to 90 min after alcohol consumption)
- Serum SHBG (nmol/l)(from 40 min before to 90 min after alcohol consumption)
- Serum ethanol (g/l)(from 40 min before to 90 min after alcohol consumption)
研究者
Professor Lars Ove Dragsted
Professor, Head of Section
University of Copenhagen