Clinical trial NCT04847011: Deciphering the Impact of Exposures From the Gut Microbiome-derived Molecular Complex in Human Health and Disease
Official title: Deciphering the Impact of Exposures From the Gut Microbiome-derived Molecular Complex in Human Health and Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rheumatoid Arthritis
Parkinson Disease
Healthy
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: University of Luxembourg
name: Paracelsus-Elena-Klinik Kassel
First posted: 2021-04-15
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The ExpoBiome project will analyze the impact of fasting on patients with Parkinsons's Disease (PD) or rheumatoid arthritis (RA) on a clinical level as well as the effect of fasting on their immune system and gut microbiota. ExpoBiome will combine metagenomics and other "omics" \[meta-transcriptomics, meta-proteomics and (meta-)metabolomics\], bioinformatic analyses and biostatistics under a systems biology framework to gain new mechanistic insights into microbiome-immune system interactions in the context of chronic diseases with inflammatory signatures.

Besides a one time crossectional study of healthy participants, patients with RA and PD a longitudinal fasting study with two arms (RA and PD) is planned.

Detailed description: The human gut microbiome is a complex ecosystem, which contributes essential functions to human physiology. Changes to the microbiome are associated with several chronic diseases characterised by inflammation, including neurodegenerative and autoimmune diseases. Microbiome-derived effector molecules comprising nucleic acids, (poly)peptides and metabolites are present at high levels in the gut but have so far eluded systematic study. This gap in knowledge is limiting mechanistic understanding of the microbiome's functional impact on chronic diseases such as Parkinson's Disease (PD) and rheumatoid arthritis (RA). Here, for the first time a combination of advanced high-resolution methodologies will be integrated to comprehensively identify the constituents of this molecular complex and their impact on the human immune system. First, a quantitative, integrated multi-omic analysis on microbiome samples collected from healthy individuals and patients with newly diagnosed PD or RA will be performes.

Using contextualised prior knowledge (ExpoBiome Map) and machine learning methods, we will identify microbial molecules associated with condition-specific immunophenotypes. Second, the biomarker signature during a model clinical intervention (therapeutic fasting) will be validated and tracked to predict treatment outcomes. Third, microbes and molecules will be screened in personalised HuMiX gut-on-chip models to identify novel anti-inflammatory compounds. By providing mechanistic insights into the molecular basis of human-microbiome interactions, the project will generate essential new knowledge about causal relationships between the gut microbiome and the immune system in health and disease. By facilitating the elucidation of currently unknown microbiome-derived molecules, it will identify new genes, proteins,metabolites and host pathways for the development of future diagnostic and therapeutic applications.

Eligibility criteria: Inclusion Criteria:

* One of the following diagnoses: rheumatoid arthritis (first diagnosis \>6 weeks ago and \<8 years), parkinson's disease OR healthy volunteer
* Control ("healthy") individuals must be without any evidence of active, known or treated RA, without any evidence of active, known or treated central nervous system disease, and without a known family history of idiopathic PD
* Arthritis in at least one joint
* Control individuals should match the RA or PD individuals as closely as possible, especially their age, sex, and education
* Present written declaration of consent
* Consent to specimen collection and specimen use
* Ability to understand the patient information and willingness to sign the consent form

Exclusion Criteria:

* gout or proven bacterial arthritis
* Psychiatric illness that limits understanding of the examination protocol (unable to consent)
* BMI \< 18.5
* Pre-existing/current eating disorders (bulimia nervosa, anorexia nervosa) within the past 5 years.
* Severe internal diseases (e.g. renal insufficiency with creatinine \> 2mg/dl)
* Participation in another study
* Existing vegan diet or fasting within the past 6 months
* Pregnancy or breastfeeding
* Chronic inflammatory bowel disease
* Use of antibiotics within the past 12 months
* Presence of anemia

Primary outcomes:
measure: Gut microbiota Characterization
timeFrame: Change over baseline to 12 months
Secondary outcomes:
measure: Resting blood pressure
timeFrame: Change over baseline to 12 months
measure: Heart rate
timeFrame: Change over baseline to 12 months
measure: Abdominal circumference
timeFrame: Change over baseline to 12 months
measure: Waist to Hip Ratio
timeFrame: Change over baseline to 12 months
measure: Body Mass Index (kg/m2)
timeFrame: Change over baseline to 12 months
measure: Disease Activity Score 28 (DAS-28-CRP)
timeFrame: Change over baseline to 12 months
measure: Health Assessement Questionnaire (HAQ)
timeFrame: Change over baseline to 12 months
measure: Simplified Disease Activity Index Score (SDAI)
timeFrame: Change over baseline to 12 months
measure: Hannover Functional Ability Questionnaire (Funktionsfragebogen Hannover, FFbH-R)
timeFrame: Change over baseline to 12 months
measure: MDS-UPDRS
timeFrame: Change over baseline to 12 months
measure: Parkinson's Disease Sleep Scale-2 (PDSS-2)
timeFrame: Change over baseline to 12 months
measure: Parkinson's Disease Questionnaire-39 (PDQ-39)
timeFrame: Change over baseline to 12 months
measure: Non-motor symptoms questionnaire (NMSQ)
timeFrame: Change over baseline to 12 months
measure: Non Motor Symptoms Scale (NMSS)
timeFrame: Change over baseline to 12 months
measure: Stress questionnaire (Cohen Perceived Stress Scale, CPSS)
timeFrame: Change over baseline to 12 months
measure: Quality of Life questionnaire (WHO-5)
timeFrame: Change over baseline to 12 months
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Change over baseline to 12 months
measure: Mood questionnaire (Profile of Mood States, POMS)
timeFrame: Change over baseline to 12 months
measure: Sociodemographic Measurements
timeFrame: Baseline
measure: Behavioral Factors
timeFrame: Change over baseline to 12 months
measure: Dietary Behaviour
timeFrame: Change over baseline to 12 months
measure: Behavioral Factors: alcohol consumption
timeFrame: Change over baseline to 12 months
measure: Behavioral Factors: smoking
timeFrame: Baseline
measure: Expectation questions
timeFrame: Baseline
measure: Differential blood count
timeFrame: Change over baseline to 12 months
measure: Hepatic transaminases (GPT, GOT) and Gamma glutamyl transpeptidase (y-GT)
timeFrame: Change over baseline to 12 months
measure: Bilirubine (total, direct, indirect in mg/dL)
timeFrame: Change over baseline to 12 months
measure: Total protein in grams per liter (g/L)
timeFrame: Change over baseline to 12 months
measure: Albumine in grams per liter (g/L)
timeFrame: Change over baseline to 12 months
measure: Creatinine in µmol per liter (µmol/L)
timeFrame: Change over baseline to 12 months
measure: Estimated glomerular filtration rate (eGFR) in milliliter per minute (mL/min)
timeFrame: Change over baseline to 12 months
measure: Alcalic Phosphatase in units per liter (U/L)
timeFrame: Change over baseline to 12 months
measure: Urea in milligrams per deciliter (mg/dL)
timeFrame: Change over baseline to 12 months
measure: Blood lipids and fasting glucose
timeFrame: Change over baseline to 12 months
measure: HbA1C (mmol/mol Hb, %)
timeFrame: Change over baseline to 12 months
measure: TSH (mU/L)
timeFrame: Change over baseline to 12 months
measure: IGF-1 (ng/mL)
timeFrame: Change over baseline to 12 months
measure: Insulin (mU/L)
timeFrame: Change over baseline to 12 months
measure: High sensitive CrP (mg/L)
timeFrame: Change over baseline to 12 months
measure: Rheumatoid factor (RF, IgM) (U/mL)
timeFrame: Baseline
measure: Anti-cyclic citrullinated peptide (ACPA) (U/mL)
timeFrame: Change over baseline to 12 months
measure: Zonulin (ng/mL)
timeFrame: Change over baseline to 12 months
measure: Fatty acid binding protein 2 (FABP2) (pg/mL)
timeFrame: Change over baseline to 12 months
measure: Plasma Calprotectin (µg/g)
timeFrame: Change over baseline to 12 months
measure: Fecal Calprotectin (µg/g)
timeFrame: Change over baseline to 12 months
measure: Phenotyping of immune cells
timeFrame: Change over baseline to 12 months
measure: Urine metabolomics (10 ml midstream urine)
timeFrame: Change over baseline to 12 months
measure: Oral microbiota analysis in saliva
timeFrame: Change over baseline to 12 months
Other outcomes:
Locations:
city: Kassel
country: Germany
facility: Paracelsus-Elena-Klinik Kassel
state: Hessen
city: Berlin
country: Germany
facility: Charité Hochschulambulanz für Naturheilkunde am Immanuel Krankenhaus
Study officials:
affiliation: Charite - Universitätsmedizin Berlin
name: Andreas Michalsen, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: