The Kinetics of Autophagy During Periodic Fasting in Healthy People and Patients With Rheumatoid Arthritis or Metabolic Syndrome - an Exploratory Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Exploratory Proteomics of Autophagy Processes I
研究概览
简要总结
Autophagy is considered one of the key molecular mechanisms for the broad preventive and therapeutic effects of periodic fasting. While it is generally known that fasting induces autophagy, there are no human studies that focus on the size and temporal kinetics of autophagy and its association with fasting specific signaling pathways. The kinetics of autophagy in patients with chronic diseases will now be compared with the kinetics of autophagy in healthy subjects, who both fast according to the same scheme; and further changes in metabolic and inflammatory parameters will be investigated.
详细描述
Therapeutic fasting has been used for many decades in naturopathy and integrative medicine clinically successfully in the treatment of chronic diseases and pain syndromes. In particular, fasting therapy is used for chronic rheumatic, inflammatory, and metabolic diseases with increasing patient demand in specialized clinical facilities (fasting clinics).
Within the various historically developed forms of fasting, the fasting program according to the Buchinger Wilhelmi method has established itself worldwide as the most frequently applied method. This involves a subtotal caloric restriction with a daily caloric intake (200-400kcal/day) in the form of liquid components over a defined period of at least 10 days, accompanied by supporting measures of a health-promoting lifestyle program with elements such as exercise therapy, manual procedures, stress reduction and hydro-balneotherapy.
In early randomized studies and a systematic review, the effectiveness of inpatient fasting therapy for patients with rheumatoid arthritis was proven with 1a evidence. For the other indications, there is mainly empirical evidence or data from observation or prospective uncontrolled studies. In recent years, extensive basic science research activity has developed in the area of caloric restriction and intermittent fasting. In this context, a large number of favorable animal experimental findings have been demonstrated by defined fasting periods, including reductions in insulin, IGF-1, increases in adiponectins, insulin sensitivity, neurotrophic factors, and, over longer observation periods, a decrease in the incidence of cardiovascular, inflammatory, and metabolic, and more recently oncological diseases in a wide variety of animal species.
Numerous experimental studies have demonstrated that fasting or total or subtotal caloric restriction is a potent inducer of cellular autophagy. For autophagy, numerous beneficial effects on chronic diseases or disease defense functions have now been experimentally documented and also hypothesized for humans, including neurodegenerative and metabolic diseases, but also acute infections and inflammatory diseases. Unclear to date is the kinetics of the autophagy enhancing effect of fasting. In theoretical transfer from animal experimental data, an increase is postulated between 12 and 36h of fasting and possibly a decrease after several days.
Against this background, autophagy will now be investigated for the first time in blood samples from fasting healthy and diseased individuals in an exploratory clinical study.
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
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •One of the following diagnoses: rheumatoid arthritis, metabolic syndrome OR healthy volunteer
- •Beginning (first 24h) inpatient treatment or hospital stay at Immanuel Hospital Berlin, Department of Naturopathy OR healthy volunteer
- •Present written declaration of consent
排除标准
- •Insufficient linguistic communication
- •Dementia or other cognitive disorder
- •Pregnancy or lactation
- •Simultaneous participation in another clinical trial
结局指标
主要结局
Exploratory Proteomics of Autophagy Processes I
时间窗: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
- Change in protein levels of autophagy biomarkers (LC3II \& p62) of isolated PBMCs (peripheral blood mononuclear cells) by Western Blotting, change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
Exploratory Proteomics of Autophagy Processes II
时间窗: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
- Change in protein levels and protein phosphorylation by untargeted mass spectrometry-based proteomics and phosphoproteomics of isolated PBMCs (peripheral blood mononuclear cells), change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
次要结局
- Waist to Hip Ratio(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Rheumatoid factor (RF, IgM) (U/mL)(Day 1 (baseline))
- Body fat(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Body Mass Index (kg/m2)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Resting blood pressure(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Cutaneous carotenoid level (CCL)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Heart rate(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Health Assessement Questionnaire (HAQ)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Quality of Life questionnaire (WHO-5)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Behavioral Factors: alcohol consumption(Day 1 (baseline), after 2 and 6 weeks)
- Muscle mass(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Mood questionnaire (Profile of Mood States, POMS)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Sociodemographic Measurements(Day 1 (baseline))
- Behavioral Factors(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Behavioral Factors: fasting experience(Day 1 (baseline))
- Expectation questions(Day 1 (baseline))
- Erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/h)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Anti-cyclic citrullinated peptide (ACPA) (U/mL)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Metabolic processes(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Lipid profiling(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Disease Activity Score 28 (DAS-28-CRP)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Simplified Disease Activity Index Score (SDAI)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Stress questionnaire (Cohen Perceived Stress Scale, CPSS)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- General Self-efficacy Short Scale (ASKU)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Electrolytes(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Mindful Attention Awareness Scale (MAAS)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Creatinine in µmol per liter (µmol/L)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Blood lipids and fasting glucose(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Insulin (mU/L)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- CrP (mg/L)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Transcription expression patterns(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Numerical Analog Scales(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Hospital Anxiety and Depression Scale (HADS)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Behavioral Factors: smoking(Day 1 (baseline), after 2 and 6 weeks)
- Estimated glomerular filtration rate (eGFR) in milliliter per minute (mL/min)(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- ß-Hydroxybutyrate(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Proteome/phosphoproteome/ubiquitinome patterns(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Epigentic patterns(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
- Exosomal protein patterns(change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up)
研究者
Andreas Michalsen
Prof. Dr. med.
Charite University, Berlin, Germany