Clinical trial NCT04739852: An Exploratory Clinical Study on Autophagy During Fasting
Official title: The Kinetics of Autophagy During Periodic Fasting in Healthy People and Patients With Rheumatoid Arthritis or Metabolic Syndrome - an Exploratory Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Arthritis, Rheumatoid
Syndrome, Metabolic
Healthy
Keywords: Fasting
Autophagy
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Bonn AöR
First posted: 2021-02-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3 groups of different inclusion criteria (healthy, metabolic syndrome or rheumatoid arthritis) undergoing the same intervention
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Insufficient linguistic communication
* Dementia or other cognitive disorder
* Pregnancy or lactation
* Simultaneous participation in another clinical trial

Primary outcomes:
measure: Exploratory Proteomics of Autophagy Processes I
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Exploratory Proteomics of Autophagy Processes II
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
Secondary outcomes:
measure: Muscle mass
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Body fat
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Resting blood pressure
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Cutaneous carotenoid level (CCL)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Heart rate
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Waist to Hip Ratio
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Body Mass Index (kg/m2)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Disease Activity Score 28 (DAS-28-CRP)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Health Assessement Questionnaire (HAQ)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Simplified Disease Activity Index Score (SDAI)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Stress questionnaire (Cohen Perceived Stress Scale, CPSS)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Mindful Attention Awareness Scale (MAAS)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Numerical Analog Scales
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Quality of Life questionnaire (WHO-5)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: General Self-efficacy Short Scale (ASKU)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Mood questionnaire (Profile of Mood States, POMS)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Sociodemographic Measurements
timeFrame: Day 1 (baseline)
measure: Behavioral Factors
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Behavioral Factors: alcohol consumption
timeFrame: Day 1 (baseline), after 2 and 6 weeks
measure: Behavioral Factors: smoking
timeFrame: Day 1 (baseline), after 2 and 6 weeks
measure: Behavioral Factors: fasting experience
timeFrame: Day 1 (baseline)
measure: Expectation questions
timeFrame: Day 1 (baseline)
measure: Creatinine in µmol per liter (µmol/L)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Estimated glomerular filtration rate (eGFR) in milliliter per minute (mL/min)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Electrolytes
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Blood lipids and fasting glucose
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Insulin (mU/L)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: ß-Hydroxybutyrate
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: CrP (mg/L)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/h)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Rheumatoid factor (RF, IgM) (U/mL)
timeFrame: Day 1 (baseline)
measure: Anti-cyclic citrullinated peptide (ACPA) (U/mL)
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Metabolic processes
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Lipid profiling
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Transcription expression patterns
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Proteome/phosphoproteome/ubiquitinome patterns
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Epigentic patterns
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
measure: Exosomal protein patterns
timeFrame: change from baseline over 5 fasting days, to day 3 refeeding and to 7 days follow up
Other outcomes:
measure: Final questionnaire to record tolerability of fasting and nutrition, adverse effects
timeFrame: After 6 weeks
Locations:
city: Berlin
country: Germany
facility: Hochschulambulanz für Naturheilkunde der Charité-Universitätsmedizin Berlin am Immanuel-Krankenhaus
Study officials:
affiliation: Charite - Universitätsmedizin Berlin
name: Andreas Michalsen, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Psychiatry and Psychotherapy University Bonn, Clinical Centre
name: Nils Gassen, Dr.
role: STUDY_DIRECTOR
References: