BIOMIS-Gastr: Establishment of the Human Intestinal and Salivary Microbiota Biobank - Gastrointestinal Diseases

Sponsor

Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari (Other)

Overall Status

Completed

CT.gov ID

NCT04698148

Collaborator

Istituti Tumori Giovanni Paolo II (Other), University of Bari Aldo Moro (Other), University of Salento (Other), Università degli Studi di Perugia (Other), Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (Other), Catholic University of the Sacred Heart (Other)

225

Enrollment

Locations

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, clinical, multicentre study aimed to collect biological samples and study microbiota from subjects with Clostridium Difficile (CDI), subjects affected by Multi Drug Resistant Organisms (MDRO) infection, subjects with Chronic Inflammatory Bowel Disease (IBD), subjects with Irritable Bowel Syndrome (IBS), subjects with Hepatic Encephalopathy and from healthy volunteers. Microbiota is a complex consortium of microorganisms, located at the mucosal level (in particular intestinal, oral and vaginal) having a key role in human health and in the onset of several diseases. Microbiota alterations have been found in several diseases (gastrointestinal, metabolic, renal, oncological, gynaecological)

The study will allow to:

Provide biological samples (faeces, saliva, blood, urine) from healthy volunteers and patients to the first Italian microbiota biobank;
Study microorganisms using different in vitro and in vivo techniques;
Study the link between the microbiota and the disease. This study is part of the BIOMIS project (Project Code: ARS01_01220), presented as part of the "Avviso per la presentazione di progetti di ricerca industriale e sviluppo sperimentale nelle 12 aree di specializzazione individuate dal PNR 2015-2020" and admitted to funding under the National Operational Program "Ricerca e Innovazione" 2014-2020 by directorial decree of MIUR - Department for Higher Education and Research - n. 2298 of 12 September 2018. BIOMIS includes several clinical studies that enrol patients with different pathologies to collect and store biological samples and study microbiota.

Condition or Disease	Intervention/Treatment	Phase
Clostridium Difficile Infection Multi Drug Resistant Organisms Chronic Inflammatory Bowel Disease Irritable Bowel Syndrome Hepatic Encephalopathy	Other: Biological sample collection Other: Questionnaire Other: Medical examination

Detailed Description

The primary aim of this multicentric study is to populate the first national microbioma biobank with biological samples (fecal, salivary, urinary and blood samples) subjects suffering from selected disease (CDI, MDRO, IBD, IBS and Hepatic Encephalopathy), and healthy volunteers.

The secondary aim is the characterization of microorganisms of the biobank and study of the microbiota-pathology relationship using meta-omics, in vitro and in vivo approaches.

The study plans to enrol 225 subjects at Policlinico of Bari, University of Perugia and Policlinico Agostino Gemelli Rome, according to the inclusion/exclusion criteria. The study participation is voluntary, and the subjects have the right to withdraw from the study at any time and for any reason.

During the study, 3 visits are planned:

Visit 0 (V0), including description of the objectives and procedures study, signature written informed consent, inclusion/exclusion criteria evaluation, medical examination (blood pressure measurement, abdominal and thoracic physical examination), filling in of the anamnestic questionnaire, delivery of the coproculture kit, delivery of kits for the collection of fecal, salivary and urinary material to be reported at Visit 1 and delivery of a 3-day food diary, to be completed autonomously in the days preceding the Visit 1.
Visit 1 (V1) - at least 4 days after V0, including delivery of the of the collected biological material (feces, saliva, urine), and of a 3-day food diary, filling in of the new signs and symptoms anamnestic questionnaire and blood sampling by medical staff. For MDRO patients rectal swab collection.
Telephone evaluation: administration of a "Food Frequency Questionnaire" to assess the subjects' alimentary habits.

Standard Operative Procedures (SOP) for samples storing, transport and processing will be adopted to ensure samples stability and grant results validity and quality.

Following collections, samples will be processed in different aliquots that will be used for:

routine screening;
storage in the first Italian human microbiote biobank (I.R.C.C.S. - Istituto Tumori "Giovanni Paolo II", Bari);
evaluation of the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile;
Evaluation of the transcriptomic profile of PBMCs of healthy subjects and subjects affected by selected pathologies and evaluation of the serum proteomic profile Furthermore, molecular characterization of pathogenic microorganisms and pathogenic biotypes (pathovars) of commensal species of subjects with selected pathologies will be conducted.

Part of the biological material will be used for animal studies on the physiopathological role of the human intestinal microbiota transplanted into mouse models of pathology and Germ-free mouse models (specific animal study protocol developed).

Also, in vitro studies on mucosal models to evaluate the interaction between the microbiota and the intestinal mucosa will be conducted.

The study foresees no more than minimal risk associated with blood sampling procedures. All the necessary measures to avoid any risks / inconveniences resulting from participation of the subject under study will be taken.

The study is compliant with Good Clinical Practice. Study protocol and all related documents have been approved by approved by the Independent Ethics Committees (IEC) of the involved clinical sites.

To ensure the protection and confidentiality of the participants' data, all study activities will be carried out in accordance with the European General Data Protection Regulation, Regulation (EU) 2016/679, which repeals Directive 95/46/EC.

Study Design

Study Type:

Observational

Actual Enrollment :

225 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Costituzione Della Biobanca Del Microbiota Intestinale e Salivare Umano: Dalla Disbiosi Alla Simbiosi

Actual Study Start Date :

Feb 8, 2021

Actual Primary Completion Date :

May 10, 2022

Actual Study Completion Date :

May 10, 2022

Arms and Interventions

Arm	Intervention/Treatment
CDI patients Patients with Clostridium Difficile Infection	Other: Biological sample collection Collection of faeces, coproculture examination, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening. Analysis for the identification, quantification and characterization of health-promoting bacteria Other: Questionnaire Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire Other: Medical examination Blood pressure measurement, abdominal and thoracic physical examination
MDRO patients Patients with Multi Drug Resistant Organisms infection	Other: Biological sample collection Collection of faeces, coproculture examination, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening. Analysis for the identification, quantification and characterization of health-promoting bacteria Other: Questionnaire Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire Other: Medical examination Blood pressure measurement, abdominal and thoracic physical examination
IBD patients Patients with Chronic Inflammatory Bowel Disease	Other: Biological sample collection Collection of faeces, coproculture examination, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening. Analysis for the identification, quantification and characterization of health-promoting bacteria Other: Questionnaire Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire Other: Medical examination Blood pressure measurement, abdominal and thoracic physical examination
IBS patients Patients with Irritable Bowel Syndrome	Other: Biological sample collection Collection of faeces, coproculture examination, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening. Analysis for the identification, quantification and characterization of health-promoting bacteria Other: Questionnaire Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire Other: Medical examination Blood pressure measurement, abdominal and thoracic physical examination
Hepatic Encephalopathy patients Patients with Hepatic Encephalopathy	Other: Biological sample collection Collection of faeces, coproculture examination, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening. Analysis for the identification, quantification and characterization of health-promoting bacteria Other: Questionnaire Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire Other: Medical examination Blood pressure measurement, abdominal and thoracic physical examination
healthy volunteers healthy volunteers	Other: Biological sample collection Collection of faeces, coproculture examination, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening. Analysis for the identification, quantification and characterization of health-promoting bacteria Other: Questionnaire Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire Other: Medical examination Blood pressure measurement, abdominal and thoracic physical examination

Outcome Measures

Primary Outcome Measures

Biological samples collection for establishment of the first National Microbiome Biobank [through study completion, an average of 1 year]
Recruitment of 225 subjects (CDI, MDRO, IBD, IBS, Hepatic Encephalopathy patients and healthy volunteers) to collect biological samples for establishment of the first National Microbiome Biobank

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

HEALTHY VOLUNTEERS

healthy subjects aged between 18 and 60 years
BMI between 18.5-30
omnivorous diet
signature of the informed consent

PATIENTS WITH CDI

subjects with CDI > 18 years
Symptomatic recurrent CDI infection, diagnosed by toxin search (ELISA)
Subjects eligible for antibiotic treatment in accordance with European guidelines
Possibility of being subjected to the diagnostic and therapeutic procedures of the study
Negative parasitological examination of stools for Giardia lamblia, Entamoeba histolytica / dispar, Cryptosporidium parvum, and other parasites.
Negativity of co-culture for Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogenic Escherichia coli and other microorganisms with the exception of Clostridium difficile
Negativity of the following serological tests: HAV-IgM, HBsAg, Anti-HCV, Anti-HIV1-2, VDRL
Signature of the informed consent

PATIENTS WITH MDRO

Subjects > 18 years old
Subjects colonised for MDRO diagnosed with rectal swab
Negative parasitological faeces culture for Giardia lamblia, Entamoeba histolytica / dispar, Cryptosporidium parvum and other parasites.
Negative faeces culture for C. difficile, Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogens Escherichia coli
Signature of informed consent.

PATIENTS WITH IBD

Age> 18 years.
Individuals available for scheduled visits, treatment plan, laboratory tests, lifestyle guidelines, and other study procedures.
Subjects with a documented diagnosis of ulcerative colitis or Crohn's at least 6 months before screening.
Signature of informed consent.

PATIENTS WITH IBS

Subjects diagnosed with IBS according to Rome IV criteria
Age between 18 and 60 years
BMI between 18.5-30
Omnivorous diet
Signature of informed consent

PATIENTS WITH HEPATIC ENCEPHALOPATHY

Subjects with hepatic encephalopathy
Age between 18 and 60 years
BMI between 18.5-30
Omnivorous diet
Signature of informed consent

Exclusion criteria:

Healthy volunteers

Current or previous infectious diseases (HAV, HBV, HCV, HIV, Cytomegalovirus, Epstein-Barr virus)
Chronic liver disease
History of Clostridium difficile infections
Recent (<3 months) therapy with antibiotics, immunosuppressive drugs, chemotherapy
Chronic therapy with proton pump inhibitors
Recent (<3 months) use of probiotics, laxatives or other aids (drugs / supplements) for the regulation of gastrointestinal activity
Previous history of organ / tissue transplantation
Recent onset of diarrhea
Chronic diarrhea
Chronic constipation
Previous gastrointestinal surgery (eg gastric bypass)
Recurring urinary tract infections (3 cases per year)
Previous major acute cardiovascular diseases (myocardial infarction, stroke)
Type 2 diabetes mellitus
Hypertension
eGFR (estimated glomerular filtration rate) lower than 60ml / minute and / or diagnosis of nephropathy
Chronic gastrointestinal disorders
Systemic inflammatory diseases
Suspicion, clinical diagnosis or previous history of cancer (<5 years)
Autoimmune disorders or history of chronic and systemic autoimmune disorders
Neurodegenerative disorders
Pregnancy and breastfeeding
Healthcare workers
Operators work with animals
Psychiatric conditions that reduce protocol compliance.

Patients with CDI

Age <18 years
Negative detection of Clostridium difficile toxin in faeces by ELISA method
Severe clinical condition (sepsis, severe dehydration, important co-morbidities)
Previous i.c. total or partial colectomy
High risk of post-colonoscopy complications
Other causes of symptoms similar to those caused by CDI, such as other infections, inflammatory bowel diseases or irritable bowel syndrome
Positive parasitological examination of stool for Giardia lamblia, Entamoeba histolytica / dispar, Cryptosporidium parvum, and other parasites
Copro-culture positive for Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogenic Escherichia coli and other microorganisms except for Clostridium difficile
Positivity of the following serological tests: HAV-IgM, HBsAg, Anti-HCV, Anti-HIV1-2, VDRL
Pregnancy or breastfeeding
Psychiatric conditions that reduce protocol compliance

Patients with MDRO

Subjects <18
Subjects unable to perform or intolerant to lower endoscopy
Subjects negative for rectal swab MDRO
Positivity for parasitological faeces culture for Giardia lamblia, Entamoeba histolytica / dispar, Cryptosporidium parvum and other parasites.
Positive faeces culture for C. difficile, Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogens Escherichia coli.
Subjects being treated with cyclosporine, mycophenolate or tacrolimus
Women who are pregnant or breastfeeding
Psychiatric conditions that reduce protocol compliance

Patients with IBD

Subjects <18 years.
Subjects diagnosed with not determined colitis
Patients with significant comorbidities (sepsis, severe trauma within the last 4 weeks, NYHA class IV heart failure)
Patients with symptoms compatible with those caused by IBD, such as infectious colitis, irritable bowel syndrome, ischemic colitis, actinic colitis.
Subjects receiving or expected to receive cyclosporine, mycophenolate or tacrolimus within 4 weeks of the first day study visit.
Positivity for parasitological faeces culture for Giardia lamblia, Entamoeba histolytica / dispar, Cryptosporidium parvum and other parasites.
Positive faeces culture for C. difficile, Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogens Escherichia coli.
Patients diagnosed with primary sclerosing cholangitis.
Women who are pregnant or breastfeeding.
Psychiatric conditions that reduce protocol compliance

Patients with IBS

Current or previous infectious diseases (HAV, HBV, HCV, HIV, Cytomegalovirus, Epstein-Barr virus)
Chronic liver disease
History of C. difficile infections
Recent (<3 months) therapy with antibiotics, immunosuppressive drugs, chemotherapy
Chronic therapy with proton pump inhibitors
Previous history of organ / tissue transplantation
Previous gastrointestinal surgery (eg gastric bypass)
Recurrent urinary tract infections (3 cases per year)
Previous major acute cardiovascular diseases (myocardial infarction, stroke)
Type 2 diabetes mellitus
eGFR lower than 60ml / minute and / or diagnosis of nephropathy
Systemic inflammatory diseases
Suspicion, clinical diagnosis or previous history of cancer (<5 years)
Autoimmune disorders or history of chronic and systemic autoimmune disorders
Neurodegenerative disorders
Pregnancy and breastfeeding
Psychiatric conditions that reduce protocol compliance.

Patients with hepatic encefalopathy

History of C. difficile infections
Chronic therapy with proton pump inhibitors
Previous history of organ / tissue transplantation
Recent emergence of diarrhea
Chronic diarrhea
Previous gastrointestinal surgery (eg gastric bypass)
Recurring urinary tract infections (3 cases per year)
Previous major acute cardiovascular diseases (myocardial infarction, stroke)
Type 2 diabetes mellitus
eGFR lower than 60ml / minute and / or diagnosis of nephropathy
Systemic inflammatory diseases
Suspicion, clinical diagnosis or previous history of cancer (<5 years)
Autoimmune disorders or history of chronic and systemic autoimmune disorders
Pregnancy and breastfeeding
Psychiatric conditions that reduce protocol compliance

Contacts and Locations

Locations

	Site	City	Country
1	Azienda Ospedaliera Universitaria Policlinico di Bari - Sezione di Malattie dell'Apparato Digerente, Endoscopia e Trapianto di Fegato (D.E.T.O.)	Bari	Italy
2	Università degli Studi di Perugia - Dipartimento di Medicina	Perugia	Italy
3	Centro Malattie Apparato Digerente - CEMAD, Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore	Roma	Italy