Oral and Gut Microbiota Changes During Long-term Fasting in Humans (OralFast)
Primary Purpose
Healthy, Periodontitis
Status
Completed
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Long-term fasting
Sponsored by
About this trial
This is an interventional prevention trial for Healthy focused on measuring oral microbiota, intestinal microbiota, inflammatory status, redox status, sulfur metabolism, halitosis
Eligibility Criteria
Inclusion Criteria:
- Both subjects with periodontitis and healthy periodontium will be included.
- Signed informed consent
Exclusion Criteria:
- Not able to sign the informed consent
- diagnosticated with cachexia, anorexia, nervosa, advanced kidney, liver or cerebrovascular insufficiency
- Smoking
- the intake of antibiotics within the last 8 weeks, as well as the intake of probiotics within the last 4 weeks
- periodontal treatment in the last 6 months
- chronic manifest psychical and psychiatric diseases
- participation in another study
- pregnancy or breastfeeding
Sites / Locations
- Buchinger Wilhelmi clinic
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Long-term fasting
Arm Description
Long-term fasting according to the Buchinger Wilhelmi fasting program.
Outcomes
Primary Outcome Measures
Changes in halitosis
Concentration of volatile sulfide compounds (hydrogen sulfide, methylmercaptan and dimethyl sulphide) using the OralChrome devise
Changes in microbiota compositions of subgingival microbial and plaque sampling
Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Parvimonas micra (Pm) and Prevotella intermedia (Pi) analysed by RT-q-PCR
Changes in microbiota composition in saliva
16 rRNA gene amplicon sequencing
Changes in microbiota composition in faeces
16 rRNA gene amplicon sequencing
Changes in total antioxidant capacity (TAC)
(mmol DPPH/L)
Changes in hydrogen sulfide production capacity
measured in serum and urine using the lead acetate assay
Secondary Outcome Measures
Changes in glutathione (GSH)
(µmol/g Hb)
Changes in thiobarbituric acid reactive substances (TBARS)
(µmol/L)
Changes in malondialdehyde (MDA)
nM/L
Changes in protein carbonyls
(nmol/mg protein)
Changes in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
(µL)
Changes in glutathione reductase (GR) activity
(U/g Hb)
Changes in glutathione peroxidase (GPx) activity
(U/g Hb)
Changes in peroxiredoxin activity
(U/g Hb)
Changes in catalase (CAT) activity
(U/mg Hb)
Changes in superoxide dismutase (SOD) activity
(U/g Hb)
Changes in hydroxyl radical scavenging
(mmol deoxyribose/ml)
Changes in superoxydradical scavenging
(mmol NBT/L plasma)
Changes in ABTS scavenging
(mmol/L)
Changes in reducing power
(mmol/L plasma)
Changes in thiosulfate
measured using the monobromobimane method using HPLC and LC-MS/MS
Changes in persulfidation
persulfidation in serum and urine
Changes in cystein
using the S-sulfocysteine (SSC) method which is a HPLC-based method using automated precolumn derivatization with OPA and UV detection at 338 nm in serum and urine
Changes in amino acid metabolites
using a targeted approach in serum and urine
Changes in IL-10 in blood
analysed in blood with Bio-Plex 200 Suspension array System
Changes in G-CSF in blood
analysed in blood with Bio-Plex 200 Suspension array System
Changes in IFN-γ in blood
analysed in blood with Bio-Plex 200 Suspension array System
Changes in TNF-α in blood
analysed in blood with Bio-Plex 200 Suspension array System
Changes in IL-1β in blood
analysed in blood with Bio-Plex 200 Suspension array System
Changes in IL-6 in blood
analysed in blood with Bio-Plex 200 Suspension array System
Changes in IL-8 in blood
analysed in blood with Bio-Plex 200 Suspension array System
Changes in IL-17 in blood
analysed in blood with Bio-Plex 200 Suspension array System
Changes in IL-10 in gingival crevicular fluid
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Changes in G-CSF in gingival crevicular fluid
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Changes in IFN-γ in gingival crevicular fluid
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Changes in TNF-α in gingival crevicular fluid
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Changes in IL-1β in gingival crevicular fluid
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Changes in IL-6 in gingival crevicular fluid
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Changes in IL-8 in gingival crevicular fluid
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Changes in IL-17 in gingival crevicular fluid
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Full Information
NCT ID
NCT05449249
First Posted
June 29, 2022
Last Updated
January 12, 2023
Sponsor
Buchinger Wilhelmi Development & Holding GmbH
Collaborators
Buchinger Wilhelmi Clinic, University of Geneva, Switzerland, King's College London, ETH Zurich (Switzerland)
1. Study Identification
Unique Protocol Identification Number
NCT05449249
Brief Title
Oral and Gut Microbiota Changes During Long-term Fasting in Humans
Acronym
OralFast
Official Title
Oral and Gut Microbiota Changes During Long-term Fasting in Humans
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
September 1, 2022 (Actual)
Primary Completion Date
October 8, 2022 (Actual)
Study Completion Date
January 6, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Buchinger Wilhelmi Development & Holding GmbH
Collaborators
Buchinger Wilhelmi Clinic, University of Geneva, Switzerland, King's College London, ETH Zurich (Switzerland)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this longitudinal trial is to investigate the effects of a 10±3-day fasting period in 30 subjects. Changes in the oral and gut microbiota, halitosis, as well as inflammatory and antioxidative parameters and biomarkers of sulfur metabolism will be analysed.
Detailed Description
Fasting has been linked with changes in gut microbiota as part of the physiological adaptation. Furthermore, associations have been described between oral disease and nutrition (diet rich in carbohydrates). The aim of the present longitudinal clinical study is to explore the effect of a 10±3-day fasting period on the oral and gut microbiota. 30 systemically healthy subjects attending the Buchinger Wilhelmi Clinics for fasting, will participate. Changes in oral microbiota will be assessed in plaque and saliva samples and a number of inflammatory markers will be analyzed in Gingival Crevicular fluid (GCF) and blood obtained before, during and after the fasting period. The changes in the oral microbiota will be associated to the composition of the gut microbiota. Changes in periodontal parameters and halitosis related to the fasting period will be further evaluated. Given the known association between sulfur metabolism and the redox status, parameters from the antioxidant status and oxidative damages will also be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Periodontitis
Keywords
oral microbiota, intestinal microbiota, inflammatory status, redox status, sulfur metabolism, halitosis
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
single-arm, prospective, monocentric, interventional study
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Long-term fasting
Arm Type
Experimental
Arm Description
Long-term fasting according to the Buchinger Wilhelmi fasting program.
Intervention Type
Procedure
Intervention Name(s)
Long-term fasting
Intervention Description
The participants will undergo a fasting program that includes the daily intake of 250 kcal under medical supervision.
Primary Outcome Measure Information:
Title
Changes in halitosis
Description
Concentration of volatile sulfide compounds (hydrogen sulfide, methylmercaptan and dimethyl sulphide) using the OralChrome devise
Time Frame
daily from baseline to the 3rd day of food reintroduction
Title
Changes in microbiota compositions of subgingival microbial and plaque sampling
Description
Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Parvimonas micra (Pm) and Prevotella intermedia (Pi) analysed by RT-q-PCR
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in microbiota composition in saliva
Description
16 rRNA gene amplicon sequencing
Time Frame
Baseline, fasting day 10, food reintroduction day 3, 1 and 3 months afterwards
Title
Changes in microbiota composition in faeces
Description
16 rRNA gene amplicon sequencing
Time Frame
Baseline, first spontaneous stool after food reintroduction (up to day 3), 1 and 3 months afterwards
Title
Changes in total antioxidant capacity (TAC)
Description
(mmol DPPH/L)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in hydrogen sulfide production capacity
Description
measured in serum and urine using the lead acetate assay
Time Frame
at the beginning and the end of fasting, on day 3 and 5, as well as at the food reintroduction
Secondary Outcome Measure Information:
Title
Changes in glutathione (GSH)
Description
(µmol/g Hb)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in thiobarbituric acid reactive substances (TBARS)
Description
(µmol/L)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in malondialdehyde (MDA)
Description
nM/L
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in protein carbonyls
Description
(nmol/mg protein)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
Description
(µL)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in glutathione reductase (GR) activity
Description
(U/g Hb)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in glutathione peroxidase (GPx) activity
Description
(U/g Hb)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in peroxiredoxin activity
Description
(U/g Hb)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in catalase (CAT) activity
Description
(U/mg Hb)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in superoxide dismutase (SOD) activity
Description
(U/g Hb)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in hydroxyl radical scavenging
Description
(mmol deoxyribose/ml)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in superoxydradical scavenging
Description
(mmol NBT/L plasma)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in ABTS scavenging
Description
(mmol/L)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in reducing power
Description
(mmol/L plasma)
Time Frame
Baseline, fasting day 3, 5, 10
Title
Changes in thiosulfate
Description
measured using the monobromobimane method using HPLC and LC-MS/MS
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in persulfidation
Description
persulfidation in serum and urine
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in cystein
Description
using the S-sulfocysteine (SSC) method which is a HPLC-based method using automated precolumn derivatization with OPA and UV detection at 338 nm in serum and urine
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in amino acid metabolites
Description
using a targeted approach in serum and urine
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-10 in blood
Description
analysed in blood with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in G-CSF in blood
Description
analysed in blood with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IFN-γ in blood
Description
analysed in blood with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in TNF-α in blood
Description
analysed in blood with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-1β in blood
Description
analysed in blood with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-6 in blood
Description
analysed in blood with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-8 in blood
Description
analysed in blood with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-17 in blood
Description
analysed in blood with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-10 in gingival crevicular fluid
Description
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in G-CSF in gingival crevicular fluid
Description
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IFN-γ in gingival crevicular fluid
Description
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in TNF-α in gingival crevicular fluid
Description
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-1β in gingival crevicular fluid
Description
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-6 in gingival crevicular fluid
Description
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-8 in gingival crevicular fluid
Description
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Title
Changes in IL-17 in gingival crevicular fluid
Description
analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System
Time Frame
Baseline, fasting day 10, food reintroduction day 3
Other Pre-specified Outcome Measures:
Title
Changes in Rosenberg scale
Description
organoleptic intensity scale for measuring oral malodor: 0 = no odor to 5 = intense odor
Time Frame
daily from baseline to the 3rd day of food reintroduction
Title
Changes in Seemann scale
Description
organoleptic assessment: 1 = odor noticable from 10 cm to 3 = odor noticeable from 1m
Time Frame
daily from baseline to the 3rd day of food reintroduction
Title
Changes in Ayurvedic diagnosis of the tongue
Description
examination of the tongue
Time Frame
daily from baseline to the 3rd day of food reintroduction
Title
Changes in urinary ketone bodies
Description
using ketostix
Time Frame
daily from baseline to the 3rd day of food reintroduction
Title
Changes in capillary blood ketones
Description
using GlucoMen areo 2k
Time Frame
daily from baseline to the 3rd day of food reintroduction
Title
Changes in capillary blood glucose
Description
using GlucoMen areo 2k
Time Frame
daily from baseline to the 3rd day of food reintroduction
Title
Changes in ph value of the urin
Description
using test strips
Time Frame
daily from baseline to the 3rd day of food reintroduction
Title
Changes in weight
Description
kg
Time Frame
daily from baseline to the 3rd day of food reintroduction as well as 1 and 3 months after
Title
Changes in blood pressure
Description
systolic and diastolic in mmHg
Time Frame
daily from baseline to the 3rd day of food reintroduction as well as 1 and 3 months after
Title
Changes in pulse
Description
beats per minute
Time Frame
daily from baseline to the 3rd day of food reintroduction as well as 1 and 3 months after
Title
Plaque Index score
Description
Sillness & Loe, 1964: from 0 = no plaque to 3 = abundant plaque along the gingival margin, interdental spaces filled with plaque
Time Frame
baseline
Title
Gingival index score
Description
Löe & Sillness, 1963: from 0 = normal gingiva to 3 = severe inflammation
Time Frame
baseline
Title
Probing pocket depth
Description
Bleeding on probing, recorded as present within 30 sec (1) or absent (0)
Time Frame
baseline
Title
clinical attachment level
Description
distance between the cemento-enamel junction and the tip of the graduated steel
Time Frame
baseline
Title
recession
Description
distance between CEJ and marginal edge of the free gingiva
Time Frame
baseline
Title
Changes in leucocytes
Description
(thousands/µl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in erythrocytes
Description
(millions/µl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in haemoglobin
Description
(g/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in haematocrit
Description
(in %)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in MCV
Description
(fl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in MCH
Description
(pg)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in MCHC
Description
(g/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in thrombocytes
Description
(thousands/µl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in international normalized ratio
Description
ratio
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in Quick
Description
(in %)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in partial thromboplastin time
Description
(sec)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in aspartate aminotransferase (AST/GOT)
Description
(U/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in alanine aminotransferase (ALT/GPT)
Description
(U/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in gamma-glutamyl transferase (GGT)
Description
(U/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in alkaline phosphatase
Description
(U/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in uric acid
Description
(mg/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in urea
Description
(mg/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in glomerular Filtration Rate (GFR)
Description
(ml/min/1.73m2KOF)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in creatinine
Description
(mg/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in thyroid-stimulating hormone (TSH)
Description
(mE/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in total cholesterol
Description
(mg/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in triglyceride
Description
(mg/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in high-density lipoprotein (HDL)
Description
(mg/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in low-density lipoprotein (LDL)
Description
(mg/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in LDL / HDL - ratio
Description
ratio
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in glucose
Description
(mg/dl)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in HbA1c
Description
(mmol/mol)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in sodium
Description
(mmol/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in potassium
Description
(mmol/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in calcium
Description
(mmol/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in magnesium
Description
(mmol/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in erythrocyte sedimentation rate
Description
(mm/h)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in C - reactive protein
Description
(mg/l)
Time Frame
Baseline, fasting day 10, and food reintroduction day 3
Title
Changes in pH value of saliva
Description
(mol/l)
Time Frame
Baseline, fasting day 10, food reintroduction day 3, 1 and 3 months afterwards
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Both subjects with periodontitis and healthy periodontium will be included.
Signed informed consent
Exclusion Criteria:
Not able to sign the informed consent
diagnosticated with cachexia, anorexia, nervosa, advanced kidney, liver or cerebrovascular insufficiency
Smoking
the intake of antibiotics within the last 8 weeks, as well as the intake of probiotics within the last 4 weeks
periodontal treatment in the last 6 months
chronic manifest psychical and psychiatric diseases
participation in another study
pregnancy or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Françoise Wilhelmi de Toledo, MD
Organizational Affiliation
Buchinger Wilhelmi
Official's Role
Principal Investigator
Facility Information:
Facility Name
Buchinger Wilhelmi clinic
City
Überlingen
ZIP/Postal Code
88662
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
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Oral and Gut Microbiota Changes During Long-term Fasting in Humans
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