Clinical trial NCT04222153: Innovative Approach to Fecal Microbiota Transplantation (FMT) Applied for Chronic Kidney Disease (CKD)
Official title: Approccio Innovativo di Trapianto di Microbiota Fecale Applicato Alla Malattia Renale Cronica
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy
Chronic Kidney Diseases
Keywords: Fecal Microbiota Transplantation (FMT)
Gut microbiota
Uremic toxins
Lead sponsor: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
Sponsor class: OTHER
Collaborators: name: University of Bari Aldo Moro
First posted: 2020-01-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population is composed by healthy volunteers, aged between 18 and 50, with normal BMI and characterized by omnivorous diet.

Brief summary: The aim of this PhD project focuses on the relationship between intestinal microbiota and health in the background of Chronic Kidney Disease (CKD). Many pathologies, including the CKD, display a dysbiosis of the intestinal microbiota, which is at the same time a consequence of CKD and contributes to its progression and complication. In a variety of chronic-degenerative and infectious diseases, the "fecal microbiota transplantation" (FMT) is being tested in recent years in addition with the application of both probiotics and prebiotics. FMT is indeed currently successfully used in the eradication of recurrent Clostridium difficile infections, with success rates of 90%, thus recent evidence suggests that FMT could be applied in other diseases characterized by microbiota dysbiosis, such as CKD and diabetes, in which the FMT has never been previously tested.

This project will allow to study:

i) the prototypal production of the encapsulated suspension of healthy microbiota tested in a minimally invasive FMT procedure (by oral administration);

ii) the efficacy of the innovative prototype for colonization and modulation of intestinal microbiota following FMT;

iii) the experimental and clinical feedback of this suspension, by in vivo studies.

Detailed description: This project will allow to experiment the Fecal microbiota transplantation in the CKD model and to set up a pharmaceutical formulation of fecal suspensions of microbiota.

Firstly, a collection of fecal samples from healthy volunteers will be set up, with the aim to collect biological samples. Screening and enrollment of healthy volunteers, gathering personal and clinical information together with eating habits, will be performed.

The best product design in efficacy, stability over time as well as suitable excipients and any other active components able to perform a synergistic action will be evaluated. After defining the pharmaceutical formulation, the production of the prototype will be finalized.

In a second time in vivo studies on a model of CKD (uremic mouse with CKD induced by 5/6 nephrectomy) will be designed and carried on. The CKD model will be used to evaluate the effects and the outcomes of FMT on clinical parameters such as renal function, circulating levels of uremic toxins, state and function of the intestinal microbiota, intestinal permeability and microbiota composition. This step will be necessary to establish the efficacy of the innovative prototype for the colonization and the modulation of intestinal microbiota following FMT.

Eligibility criteria: Criteria: Healthy volunteers

Inclusion Criteria:

* Healthy subjects
* Aged between 18 and 50
* BMI between 18.5-25
* Omnivorous diet
* Informed consent signed

Exclusion Criteria:

* Health workers (to exclude the risk of transmission of multi-resistant organisms)
* Type 2 diabetes mellitus
* Hypertension
* Chronic liver disease
* Chronic gastrointestinal disorders
* Systemic inflammatory disorders
* Suspected, clinical diagnosis or previous history of malignancies (\<5 years)
* Therapies with corticosteroids or immunosuppressive drugs
* Autoimmune disorders
* Previous history of organ / tissue transplantation
* Prior gastrointestinal surgery (eg gastric bypass)
* eGFR lower than 60ml / minute and / or diagnosis of nephropathy
* Previous acute major cardiovascular diseases (myocardial infarction, stroke)
* History of C. difficile infections
* Known systemic infection not controlled
* Previous use of antibiotics (\<3 months)
* Recent appearance of diarrhea
* Chronic use of laxatives or chronic diarrhea
* Chronic constipation
* Recurrent urinary tract infections (3 cases per year)
* Use of proton pump inhibitors in the last 3 months
* Recent use of probiotics or other aids (drugs / supplements) for the regulation of gastrointestinal activity (\<3 months)
* Pregnancy and breastfeeding
* Psychiatric conditions that reduce compliance

Primary outcomes:
measure: Number of healthy volunteers enrolled according to the procedures of the FMT01 protocol
timeFrame: 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Bari
country: Italy
facility: AUO Policlinico Consorziale
state: BA
Study officials:
affiliation: Nephrology, Dialysis and Transplantation Unit "Aldo Moro" University of Bari
name: Loreto Gesualdo, MD Full Prof
role: PRINCIPAL_INVESTIGATOR
References: