Clinical trial NCT05031598: Long-term Fasting: Multi-system Adaptations in Humans
Official title: Long-term Fasting: Multi-system Adaptations in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fasting
Keywords: long-term fasting
Buchinger Wilhelmi program
magnetic resonance imaging (MRI)
magnetic resonance spectroscopy (MRS)
HDL efflux capacity
fatty acid profile in erythrocyte membrane
gut microbiota
metabolomics
hydrogen sulfide and transsulfuration pathway
Lead sponsor: Buchinger Wilhelmi Development & Holding GmbH
Sponsor class: OTHER
Collaborators: name: Buchinger Wilhelmi Clinic
name: Claude Bernard University
name: University of Milan
name: Omegametrix GmbH
name: King's College London
name: MVZ Humangenetik Ulm
name: University of Graz
name: Leiden University Medical Center
name: MVZ Labor Ravensburg
name: ETH Zurich
First posted: 2021-09-02
Enrollment: 62
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: single-arm interventional study
Primary purpose: OTHER

Brief summary: The aim of this trial is to investigate the effects of long-term fasting on size, mass, composition and function of metabolic active tissues in several organs that reexpand possibly rejuvenated after 1-4 months. Additionally, the lipid metabolism is investigated in depth.

Detailed description: Fasting displays numerous positive effects on metabolism, health and aging. Surprisingly, few considerations are given to long-term fasting periods.

The metabolic switch from food-derived glucose to adipose tissue-derived fatty acids and ketones as primary cellular fuel is the key to fasting metabolism. Fasting has been shown to improve cardiovascular risk factors and gut microbiota in humans. It provokes profound changes in lipid metabolism. However, many questions are still open concerning the mobilization, exchange, and function of lipids during long-term fasting. Furthermore, recent results show the ability of periodic restrictive nutritional strategies to trigger organ regeneration. This promising regenerative power has not been investigated comprehensively in humans. In addition, the knowledge about the role of human faecal microbiota in health and disease is increasing. Only little is known about its composition and function during fasting. We found indications that the gut microbiome could influence energy metabolism and consequently could influence the dynamic of the metabolic switch.

Long-term fasting under medical supervision according to the Buchinger Wilhelmi fasting program has been demonstrated to be safe and well-tolerated.

The current project investigates the effects of a 9±3 days fasting period by a multi-systemic approach focusing on lipid metabolism and the gut microbiome in 100 subjects. Additionally, the body composition in combination with muscle performance will be analyzed in-depth in a subgroup of 32 subjects.

Eligibility criteria: Inclusion Criteria:

* BMI between 22 - 35 kg/m2

Exclusion Criteria:

* intake of medication (cardiovascular diseases, lipid and glucose metabolism)
* chronic manifest psychical and psychiatric diseases
* participation in another study
* pregnancy or breastfeeding
* in the MRI/MRS sub-study, any MRI contraindication (claustrophobia, pacemakers, MR-incompatible prosthetic valves, metallic implants, foreign metallic body)
* active uncontrolled gastrointestinal disorders including ulcerative colitis, Crohn's disease, indeterminate colitis, severe irritable bowel syndrome, persistent infectious gastroenteritis, persistent or chronic diarrhea of unknown etiology, recurrent Clostridium difficile infection
* major surgery of the GI tract, in the past five years. Any major bowel resection at any time
* intake of antibiotics in the last 2 months

Primary outcomes:
measure: Changes in whole body composition
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in the composition of the heart
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in the composition of the liver
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in the composition of the kidney
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in the composition of the spleen
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in the composition of the quadriceps
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in the composition of the adipose tissue
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in HDL cholesterol efflux capacity
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in serum cholesterol loading capacity
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in HS-Omega-3 Index
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in faecal microbiota composition and function (carbohydrate metabolism)
timeFrame: Baseline and changes after an average of 10 (+/-3) fasting days
measure: Changes in metabolome
timeFrame: Baseline and changes after 3 fasting days, the end of fasting as well as one and four months afterwards
measure: Changes in hydrogen sulfide production capacity
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
Secondary outcomes:
measure: Changes in brain morphometry
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in cardiac mass
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in lower limbs (quadriceps, hamstrings, calves)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in lumbosacral muscle mass
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in systolic cardiac function
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in diastolic cardiac function
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in apparent diffusion coefficient (ADC)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in fiber strain (Eff)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in fractional anisotropy (FA)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in helix angle (HA)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in mean diffusivity (MD)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in cardiovascular fitness
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in muscle metabolism and mitochondrial oxidative capacity: TauPCr(s)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in muscle metabolism and mitochondrial oxidative capacity: PCr hydrolysis (%)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in muscle metabolism and mitochondrial oxidative capacity: PCr concentration
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in muscle metabolism and mitochondrial oxidative capacity: Pi concentration
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in muscle metabolism and mitochondrial oxidative capacity: ATP concentration
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in muscle metabolism and mitochondrial oxidative capacity: pH at rest and post exercise in mM
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in muscle metabolism and mitochondrial oxidative capacity: T1 of metabolites at rest
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in muscle metabolism and mitochondrial oxidative capacity: PCr consumption
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in multiparametric muscle quantification: T2
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in multiparametric muscle quantification: T2 * relaxation time
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in multiparametric muscle quantification: susceptibility (chi)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in multiparametric muscle quantification: fat fraction (PDFF)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in quadricipital maximum voluntary contraction
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in DNA methylation
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in serum amyloid A levels
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in paraoxonase (PON-1) activity
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in lipoprotein transfer enzymes
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in GlycA
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in proprotein convertase subtilisin/kexin type 9 (PCSK9)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in chylomicrons
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in oxidized phospholipids
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in enzymes
timeFrame: Baseline and changes after 3 fasting days, the end of fasting as well as one and four months afterwards
measure: Changes in persulfidation
timeFrame: Baseline, and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards
measure: Changes in sulfur compounds
timeFrame: Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards
measure: Changes in thiosulfate levels
timeFrame: Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards
measure: Changes in cysteine and cystine levels
timeFrame: Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards
measure: Changes in amino acids
timeFrame: Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards
Other outcomes:
measure: Changes in body weight
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in body mass index
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in abdominal circumference
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in resting systolic blood pressure
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in resting diastolic blood pressure
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in resting heart frequency
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in bio-electrical multifrequency impedance analysis
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in liver stiffness
timeFrame: Baseline, during and after fasting
measure: Changes in physical activity
timeFrame: Before, daily during fasting as well as one and four months afterwards
measure: Changes in circadian rhythm and sleep
timeFrame: Before, daily during fasting as well as one and four months afterwards
measure: Changes in mental well-being
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in global health
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in physical activity
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in sleep quality
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in ketonuria
timeFrame: during the fasting period and food reintroduction
measure: Changes in ketonemia
timeFrame: during the fasting period and food reintroduction
measure: Changes in glycemia
timeFrame: during the fasting period and food reintroduction
measure: Changes in dietary behaviour
timeFrame: Baseline and after fasting as well as one and four months afterwards
measure: Changes in smoking behaviour
timeFrame: Baseline and after fasting as well as one and four months afterwards
measure: Changes in alcohol consumption
timeFrame: Baseline and after fasting as well as one and four months afterwards
measure: Changes in physical activity
timeFrame: Baseline and after fasting as well as one and four months afterwards
measure: Changes in energy level
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in emotional well-being
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in physical well-being
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in symptoms: fatigue
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in symptoms: muscle weakness
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in symptoms: back pain
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in symptoms: hunger
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in symptoms: anxiety
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in symptoms: headache
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Changes in symptoms: sleep disturbances
timeFrame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards
measure: Adverse events
timeFrame: through study completion, an average of 4.5 months
measure: Changes in blood count
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in differential blood count
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in coagulation
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in liver enzymes
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in kidney parameters
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in inflammatory parameters
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in glucose metabolism
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in lipid parameters
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in electrolytes
timeFrame: Baseline and at the end of fasting as well as one and four months afterwards
measure: Changes in the immune response to fasting
timeFrame: Baseline, after 3 fasting days, and at the end of fasting as well as one and four months afterwards
measure: Changes in cell populations (natural killer and T cells)
timeFrame: Baseline, after 3 fasting days, and at the end of fasting as well as one and four months afterwards
measure: Changes in lipoprotein subclasses
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in apolipoproteins
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in lipoprotein(a)
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Changes in methylation based clocks
timeFrame: Baseline and changes at the end of fasting as well as one and four months afterwards
measure: Sociodemographic Measurements
timeFrame: Baseline
measure: Changes in nitrogen balance
timeFrame: Baseline, daily during fasting as well as food reintroduction
Locations:
city: Überlingen
country: Germany
facility: Buchinger Wilhelmi clinic
Study officials:
affiliation: Buchinger Wilhelmi Clinic
name: Françoise Wilhelmi de Toledo, Dr
role: PRINCIPAL_INVESTIGATOR
References: