Establishment of the Human Intestinal and Salivary Microbiota Biobank - Kidney Diseases

NCT ID: NCT04689074

Last Updated: 2022-08-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-02-03

Study Completion Date

2022-05-10

Brief Summary

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This is a prospective, clinical, multicentre study aimed to collect biological samples and study microbiota from subjects suffering from chronic kidney disease 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 suffering from chronic renal diseases 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.

Detailed Description

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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 chronic kidney disease (IgAN, ADPKD, advanced CKD and DKD), 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 150 subjects at Policlinic of Bari and University of Perugia, 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 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.
* 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.

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).

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.

Conditions

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Autosomal Dominant Polycystic Kidney Disease (ADPKD) Advanced-Chronic Kidney Disease (CKD) Diabetic Kidney Disease (DKD) IgA Nephropathy (IgAN)

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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ADPKD

Patients with ADPKD

Biological sample collection

Intervention Type OTHER

Collection of faeces, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening

Questionnaire

Intervention Type OTHER

Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire

Medical examination

Intervention Type OTHER

Blood pressure measurement, abdominal and thoracic physical examination

advanced CKD

Patients with advanced CKD

Biological sample collection

Intervention Type OTHER

Collection of faeces, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening

Questionnaire

Intervention Type OTHER

Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire

Medical examination

Intervention Type OTHER

Blood pressure measurement, abdominal and thoracic physical examination

DKD

Patients with DKD

Biological sample collection

Intervention Type OTHER

Collection of faeces, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening

Questionnaire

Intervention Type OTHER

Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire

Medical examination

Intervention Type OTHER

Blood pressure measurement, abdominal and thoracic physical examination

IgAN

Patients with IgAN

Biological sample collection

Intervention Type OTHER

Collection of faeces, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening

Questionnaire

Intervention Type OTHER

Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire

Medical examination

Intervention Type OTHER

Blood pressure measurement, abdominal and thoracic physical examination

Healthy volunteers

Healthy volunteers

Biological sample collection

Intervention Type OTHER

Collection of faeces, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening

Questionnaire

Intervention Type OTHER

Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire

Medical examination

Intervention Type OTHER

Blood pressure measurement, abdominal and thoracic physical examination

Interventions

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Biological sample collection

Collection of faeces, urine, saliva, PBMC and blood for biobanking, to evaluate the proteomic, metascriptomic, metabolomic, metagenomic, and metagenetic profile, and to perform routine screening

Intervention Type OTHER

Questionnaire

Anamnestic questionnaire, 3-day food questionnaire, Food Frequency Questionnaire

Intervention Type OTHER

Medical examination

Blood pressure measurement, abdominal and thoracic physical examination

Intervention Type OTHER

Eligibility Criteria

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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 ADPKD


* subjects with ADPKD aged between 18 and 60 years
* creatinine clearance between 30mL / min and 60mL / min
* creatinine clearance \> 60 mL / min
* BMI between 18.5-30
* omnivorous diet
* signature of the informed consent

PATIENTS WITH ADVANCED CKD


* subjects with advanced CDK (creatinine clearance \<30 mL / min)
* age between 18 and 60 years
* BMI between 18.5-30
* omnivorous diet
* signature of the informed consent

PATIENTS WITH IgAN


* subjects with IgAN, "progressor" (who have an increase in proteinuria or creatininemia or reduction in eGFR within the previous three years)
* subjects with IgAN, "non progressor"
* creatinine clearance\> 30 mL / min
* BMI between 18.5-30
* omnivorous diet
* signature of the informed consent

PATIENTS WITH DKD


* subjects with DKD
* subjects with A1, G1-3a staging
* subjects with A2, G1-3a staging
* subjects with staging A3, G1-3a
* creatinine clearance\> 45 mL / min
* age between 18 and 60 years
* BMI between 18.5-30
* omnivorous diet
* signature of the 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 ADPKD; PATIENTS WITH ADVANCED CKD; PATIENTS WITH IgAN; PATIENTS WITH DKD

* 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 emergence 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) occurred in the last 3 years
* 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
* Type 2 diabetes mellitus
* Pregnancy and breastfeeding
* Psychiatric conditions that reduce protocol compliance.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Of Perugia

OTHER

Sponsor Role collaborator

Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies

OTHER

Sponsor Role collaborator

Istituti Tumori Giovanni Paolo II

NETWORK

Sponsor Role collaborator

University of Salento

OTHER

Sponsor Role collaborator

University of Bari Aldo Moro

OTHER

Sponsor Role collaborator

Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Loreto Gesualdo, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari

Locations

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Nefrologia, Dialisi e Trapianto di Rene - Dipartimento dell'emergenza e dei trapianti d'organo (DETO) - Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari

Bari, , Italy

Site Status

Sezione Medicina Interna e Scienze Endocrine e Metaboliche - (MISEM) - Università degli Studi di Perugia

Perugia, , Italy

Site Status

Countries

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Italy

References

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Zhou Y, Xu H, Huang H, Li Y, Chen H, He J, Du Y, Chen Y, Zhou Y, Nie Y. Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders? Biomed Res Int. 2019 Jul 29;2019:3469754. doi: 10.1155/2019/3469754. eCollection 2019.

Reference Type BACKGROUND
PMID: 31467881 (View on PubMed)

Cosola C, Rocchetti MT, Sabatino A, Fiaccadori E, Di Iorio BR, Gesualdo L. Microbiota issue in CKD: how promising are gut-targeted approaches? J Nephrol. 2019 Feb;32(1):27-37. doi: 10.1007/s40620-018-0516-0. Epub 2018 Aug 1.

Reference Type BACKGROUND
PMID: 30069677 (View on PubMed)

Castillo-Rodriguez E, Fernandez-Prado R, Esteras R, Perez-Gomez MV, Gracia-Iguacel C, Fernandez-Fernandez B, Kanbay M, Tejedor A, Lazaro A, Ruiz-Ortega M, Gonzalez-Parra E, Sanz AB, Ortiz A, Sanchez-Nino MD. Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression. Toxins (Basel). 2018 Jul 19;10(7):300. doi: 10.3390/toxins10070300.

Reference Type BACKGROUND
PMID: 30029499 (View on PubMed)

Kanbay M, Onal EM, Afsar B, Dagel T, Yerlikaya A, Covic A, Vaziri ND. The crosstalk of gut microbiota and chronic kidney disease: role of inflammation, proteinuria, hypertension, and diabetes mellitus. Int Urol Nephrol. 2018 Aug;50(8):1453-1466. doi: 10.1007/s11255-018-1873-2. Epub 2018 May 4.

Reference Type BACKGROUND
PMID: 29728993 (View on PubMed)

Ramezani A, Massy ZA, Meijers B, Evenepoel P, Vanholder R, Raj DS. Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target. Am J Kidney Dis. 2016 Mar;67(3):483-98. doi: 10.1053/j.ajkd.2015.09.027. Epub 2015 Nov 15.

Reference Type BACKGROUND
PMID: 26590448 (View on PubMed)

Other Identifiers

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BIOMIS-Nefro

Identifier Type: -

Identifier Source: org_study_id

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