The Impact of Time-restricted Eating on the Composition of the Intestinal Microbiota and Metabolic and Neurohormonal Parameters of Women With Polycystic Ovary Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 52
- 试验地点
- 2
- 主要终点
- Change in body composition
研究概览
简要总结
Polycystic Ovary Syndrome (PCOS) is a disorder that affects approximately 10-15% of women of reproductive age. Increased activity of the hypothalamic-pituitary-ovarian (HPO) axis is considered to be one of the main factors associated with the pathogenesis of PCOS. The regulation of the activity of this axis is influenced by the following factors: insulin resistance and the activity of kisspeptins in the hypothalamus. It is suggested that intestinal dysbiosis may also play a key role in the pathogenesis of PCOS. It was noticed that the presence of bacteria producing gamma-aminobutyric acid in the intestine is positively correlated with the concentration of luteinizing hormone (LH) in the serum, which indicates the relationship between the functioning of the gut-brain axis and PCOS. A dysbiotic factor is an incorrect diet and inappropriate timing of its consumption, which may also lead to inhibition of kisspeptin expression in the hypothalamus and cause menstrual disorders.
Due to the fact that most obese women with PCOS eat significantly more meals in the second part of the day, and these meals are characterized by a significant supply of fat and simple sugars, intestinal dysbiosis seems to be an important cause of the observed disorders, while the use of chrononutrition, consisting in synchronizing meal times with endogenous 24-hour circadian rhythms may partially restore eubiosis in the intestine and improve the reproductive, metabolic and neurohormonal health of women with PCOS. Time-restricted feeding (TRF), which involves eating food usually within 8 hours followed by 16 hours of fasting, seems to be a regime that allows restoring eubiosis in the intestinal microbiota and improving the quality of life of women with PCOS. So far, only one study has been conducted among women with PCOS who used TRF for 5 weeks and a number of positive changes were demonstrated (hormonal or metabolic). However, this study did not include an assessment of the microbial and neurohormonal parameters, which seems to be a key issue.
Taking the above into account, it was hypothesized that TRF may be an appropriate therapeutic tool for women with PCOS, which will positively affect metabolic and hormonal parameters by changing the composition of the intestinal microbiota. Therefore, the main aim of the experiment is to investigate the impact of TRF on the composition of the intestinal microbiota, its metabolites, and metabolic and neurohormonal parameters in women with PCOS.
详细描述
Fifty two women, aged 18-40, will be recruited for the study. The investigators calculated the sample size using G*Power software (RRID:SCR_013726); the sample size of the participants was also determined. The effect size was calculated to be 1.04 on the basis of the differences in body fat mass between baseline values and values after 6-weeks of application of time-restricted eating by PCOS women. With an alpha value of 0.05, a sample size of eight mice per group would yield a power of 0.95.
Women recruited for the study will be provided with detailed information regarding: the purpose of the study, the study protocol, the measurements performed and the duration of the study. Recruitment will take place via social networking sites, i.e. Facebook, where target groups will be found, bringing together women with PCOS, and posts with an announcement and a contact form will be placed there. After obtaining consent to participate in the study, a group of qualified women will undergo a general medical interview by Jakub Noskiewicz, Ph.D., which will include a personal interview, including current medications and supplements taken, medical history and a basic physical examination - examination, percussion. If the interview reveals an existing infection, a chronic disease in the acute phase, a suspicion of e.g. anemia, infectious skin diseases or malnutrition, or the intake of medications constituting an exclusion criterion, the patient will not be qualified for the study. During this interview, participants will be asked to provide medical documentation confirming they suffer from PCOS.
Participants will be randomly assigned (using a specialized program) to two groups - control and intervention. Research participants assigned to the control group will receive dietary recommendations consistent with the healthy eating plate. Additionally, the recommended daily energy intake will be individually determined for each patient. Participants assigned to the TRF group will be instructed to continue eating their usual diet during the experiment (without any qualitative or quantitative restrictions), but to eat it within a limited time frame - from 9:00 a.m. to 5:00 p.m., and then fast until the next day ( protocol 8/16). The duration of the study will be 3 months (12 weeks).
A nutritional assessment of the diet will be carried out (KomPAN questionnaire). The nutritional assessment will be additionally supplemented by an interview from the last 24 hours. Then, the recruited women will be randomly assigned to the intervention group, using time-restricted nutrition, or the control group, using the principles of the healthy eating plate. The duration of the experiment will be 12 weeks, with follow-up visits scheduled at 4-week intervals. At the beginning of the experiment and at follow-up visits, women will have blood drawn (per 18 ml) to assess biochemical parameters. Each time, a stool sample will also be collected to assess the composition of the intestinal microbiota and short-chain fatty acids, and an analysis of body composition, bone density and anthropometric parameters will be carried out. During the last visit in week 12, women will be asked to fill out the KomPAN questionnaire again, which will be supplemented by an interview from the last 24 hours. Each time, an interview will be conducted regarding the women's well-being and adherence to the recommendations provided. The level of adherence to the eating window will be verified using a diary in which women will write down each day when they ate their first and last meals.
The following specific analyses are planned:
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 (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 18-40
- •suffering from Polycystic Ovary Syndrome, confirmed by appropriate medical documentation
- •BMI >25 kg^m2
排除标准
- •Taking medications regulating carbohydrate, lipid as well as medications affecting body weight in the last 3 months (will be assessed during a general medical interview conducted by Jakub Noskiewicz, MD, PhD)
- •Taking antibiotics in the last 3 months
- •Smoking in the last 3 months and alcohol consumption >100 g per week
- •Competitive sports practice
- •Significant body weight fluctuations in the 3 months before the start of the study (>5%)
- •Pregnant or breastfeeding women
- •BMI <25 kg^m2
结局指标
主要结局
Change in body composition
时间窗: Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)
Body composition will be measured using dual-energy X-ray absorptiometry (DXA) as a method that uses the phenomenon of weakening the beam of ionizing radiation passing through tissues of various densities. This method is safe and non-invasive. The mass of adipose tissue, including visceral fat tissue, the mass of lean tissue are measured (expressed in the same unit - kilograms)
Change in lipid profile
时间窗: Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)
Blood will be collected four times from the antecubital vein on an empty stomach, into test tubes with clotting granules (a single sample will amount to a total of 18 ml). The serum will be obtained by centrifugation of a venous blood clot. Total cholesterol (T-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglycerides concentrations will be determined using the Thermo Scientific Konelab 20i automatic biochemical analyzer (enzymatic method ). The nonHDL-C parameter will be calculated using the formula: nonHDL-C = T-C - HDL-C (expressed in the same unit - mg/dl or mmol/l).
Change in body weight
时间窗: Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)
Body weight measurement in a standing position, without shoes, in light clothing, on an electronic scale with an accuracy of 0.1 kg.
Change in circumferences
时间窗: Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)
Waist and hip measurements will be taken using an elastic tape. Waist circumference measurement - the tape is placed horizontally or slightly obliquely halfway between the lower edge of the ribs and the upper crest of the ilium. Measurement performed during apnea.
Change in composition of the intestinal microbiota
时间窗: Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)
Participants will be asked to provide stool samples at each scheduled meeting. Detailed instructions on sample collection and transport will be provided by the people conducting the study, and participants will receive containers containing preservative liquid. Bacterial DNA will be isolated from the provided stool samples using the QIAmp Fast DNA Stool Mini Kit. Then, the DNA will be properly secured and sent to an external company, Genomed S.A. (Warsaw, Poland), in which the assessment of microbiota will be carried out by metagenomic 16s rRNA sequencing using the V3-V4 region. Then, a bioinformatics analysis will be performed in the R environment using packages such as phyloseq, vegan, microbiome.
Change in glucose metabolism
时间窗: Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)
Blood will be collected four times from the antecubital vein on an empty stomach, into test tubes with clotting granules (a single sample will amount to a total of 18 ml). The serum will be obtained by centrifugation of a venous blood clot. Insulin concentration will be performed using the ELISA enzyme-linked immunosorbent assay, while glucose will be determined using the Thermo Scientific Konelab 20i automatic biochemical analyzer (enzymatic method ) (expressed in the same unit - mg/dl or mmol/l).
Change in selected hormonal parameters
时间窗: Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention)
Blood will be collected four times from the antecubital vein on an empty stomach, into test tubes with clotting granules (a single sample will amount to a total of 18 ml). The serum will be obtained by centrifugation of a venous blood clot. Hormonal parameters (FSH, LH, testosterone, SHBG), will be performed using the ELISA enzyme-linked immunosorbent assay (expressed in the same unit - pg/ml)
次要结局
- Change in bone density(Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention))
- Change in the expression of genes encoding kisspeptin and gamma-aminobutyric acid(Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention))
- Change in neurohormonal status(Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention))
- Assessment of changes in eating behavior pre- and post-intervention(Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention))
- Change in the concentration of short-chain fatty acids in feces(Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention))
- Change in intestinal barrier integrity(Week 0 (pre-intervention), week 4, week 8 and week 12 (post-intervention))
研究者
Joanna Bajerska
Associate Professor
Poznan University of Life Sciences