TirolGESUND: General Exercise, Smoking Undone, and Nutrition Diet
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 156
- 试验地点
- 2
- 主要终点
- Change from baseline scores of DNA methylation biomarkers of age, disease risk, and exposure
研究概览
简要总结
The goal of this clinical study is to learn about disease-risk and age-associated changes in DNA methylation patterns associated with disease risk or age in healthy women aged 30-60 in response to health-promoting lifestyle intervention (intermittent fasting or smoking cessation). The main questions the study aims to answer are:
- Are the scores of DNA methylation in epigenetic signatures associated with age, women's cancer risk, or risk exposure reduced after 6 months of lifestyle intervention compared to baseline?
- What are the dynamics of DNA methylation changes during or following intervention, and do differences in changes between different sample types exist?
- Which other biomarkers of health and disease, including metabolic changes, microbiome, clinical, mental, or inflammatory parameters, are altered following intervention?
The investigators also aim to explore whether DNA methylation changes are associated with changes in other biomarkers mentioned above.
Participants will be allocated to intermittent fasting or smoking cessation based on inclusion criteria. Intermittent fasting encompasses a 16:8 intermittent fasting schedule. Food intake is limited to an 8 h window per day with fasting for the remaining 16 h. Within the intermittent fasting study, participants are randomised to receive a ketogenic supplement (medium-chain triglyceride fibre) or not. Participants in the smoking cessation study will be guided to stop smoking. All participants will receive 1:1 personal coaching throughout the study, and will be provided with an optional exercise programme. All participants will also receive nutritional advice from a professional dietician throughout the study. Participants are invited to donate samples every 2 months for 6 months.
Researchers will compare signatures at the start and after 6 months of intervention. Within the intermittent fasting group, researchers will compare effects in individuals that received the ketogenic supplement to those that did not.
详细描述
Background and study aims: A recent study reported that a majority of malignancies may be caused modifiable risk factors and could therefore be prevented. Smoking and diet are known risk factors for cancer but also other disorders such as cardiovascular or metabolic disorders and neurodegeneration, and may promote premature cellular ageing. The investigators and others have recently described epigenetic signatures for risk of being diagnosed, or developing future, women's cancers, as well as signatures reflecting cellular ageing and exposure to risk factors such as smoking. Utilization of DNA methylation biomarkers as surrogate endpoints indicative of current and/or future disease risk could improve future efforts in preventive medicine, both by providing information on disease risk and biofeedback. Few longitudinal studies have so far investigated the effects of lifestyle changes on DNA methylation and other biomarkers of health and disease.
TirolGESUND investigates the effect of two lifestyle interventions, smoking cessation or intermittent fasting (both with additional optional exercise), over 6 months for the promotion of health and reduction of disease risk, focusing on women's cancers.
Hypothesis: Intermittent fasting or smoking cessation for a duration of 6 months result in a modulation of scores of disease risk- and age-associated DNA methylation biomarker signatures in cervical samples, indicating a reduction of disease risk, exposure, or cellular ageing.
Study design: TirolGESUND is a baseline-controlled intervention study with two parallel arms, smoking cessation and intermittent fasting. Participants are allocated to the study arm based on eligibility criteria. Within the intermittent fasting arm, participants are randomised to receive a ketogenic supplement or not. Ketosis has been suggested to elicit beneficial metabolic alterations and could therefore further enhance beneficial effects in the dietary intervention.
Endpoints: The primary endpoint are score changes in epigenetic biomarkers of cellular ageing and disease risk, primarily recently published Women's cancer risk identification (WID) indices.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women aged 30 to 60
- •Motivated to change their lifestyle
- •Smoking cessation intervention:
- •3a. Smoking cessation: ≥10 cigarettes per day for at least the last five years
- •Dietary intervention:
- •3b Dietary intervention: BMI between 25 and 35
- •NB [Nota Bene], should 3a and 3b apply, participant will be allocated to the smoking cessation intervention.
排除标准
- •Relevant underlying conditions:
- •Current or previous malignant tumour or cancer
- •Current or previous significant cardiovascular disorder [participants with elevated blood pressure are allowed to participate as long as it is well controlled under their current medication]
- •Current or previous metabolic disorder (e.g., diabetes type I or II) [in the dietary intervention arm, participants with current hypothyroidism/Morbus Hashimoto will be excluded as the switch to intermittent fasting may require a adjustment of their medication]
- •Current or previous psychiatric disorder (e.g., eating disorder, depression)
- •Current pregnancy or lactation period
- •Total hysterectomy
- •Known current or previous premalignant lesion of the cervix uteri (CIN2/3)
- •Concurrent participation in another interventional trial
结局指标
主要结局
Change from baseline scores of DNA methylation biomarkers of age, disease risk, and exposure
时间窗: Baseline, Month 6 (per participant)
Examination of change in epigenetic age, disease risk, and exposure signature scores compared to baseline (before and after intervention, i.e. baseline-controlled) in cervical samples. DNA methylation levels will be measured using the Illumina MethylationEPIC array and computed using previously described methylation indices, including: * WID-BC (Women's risk identification - Breast cancer) * WID-OC (ovarian cancer) * WID-EC (endometrial cancer) * WID-CIN (cervical intraepithelial neoplasia) * WID-REA (relative epithelial age) * WID-RIA (relative immune age) * pcgtAge (mitotic clock) * WID-SOLA\[ge\] (systemic organ life age) * WID-SMK (smoking)
次要结局
- Change in DNA methylation scores from baseline in blood samples at month 2, month 4, and month 6(Samples collected at baseline, month 2, month 4, and month 6)
- Description of study characteristics: registration rate in percent (%)(Baseline)
- Change in DNA methylation scores from baseline in cervical samples at month 2, month 4, and month 6(Samples collected at baseline, month 2, month 4, and month 6)
- Change in microbial diversity score compared to baseline, in percent (%)(Samples collected at baseline and month 6, optional month 2 and month 4)
- Description of study characteristics: compliance rate in percent (%)(Month 6 (Primary end point of study))
- Change in health-related quality of life from baseline(Baseline and month 6)
- Change in DNA methylation scores from baseline in buccal samples at month 2, month 4, and month 6(Samples collected at baseline, month 2, month 4, and month 6)
- Change of immune and inflammatory cell populations in peripheral blood(Samples collected at baseline and month 6, optional month 2 and month 4)
- Description of study characteristics: drop-out rate in percent (%)(Month 6 (Primary end point of study))
- Change in body mass index from baseline(Baseline and month 6.)
- Change in vascular health from baseline: pulse-wave velocity(Baseline and month 6.)
- Change in physical activity from baseline(Baseline and month 6)
- Change in beneficial and harmful microbial species compared to baseline, in percent (%)(Samples collected at baseline and month 6, optional month 2 and month 4)
- Change in body composition as quantified by bioelectric impedance analysis from baseline(Baseline and month 6.)
- Change in physical activity from baseline: fitness tracker data(Baseline and month 6)
- Change in smoking status from baseline(Baseline and month 6.)
- Change in physical activity from baseline: VO2max(Baseline and month 6)
- Change in pulmonary health from baseline(Baseline and month 6)
- Change in vascular health from baseline: intima-media thickness(Baseline and month 6.)
研究者
Martin Widschwendter
Study Coordinator/Co-Principal Investigator
Universitaet Innsbruck