Probiotics and Low Protein Diet in Advanced Chronic Kidney Disease

Study Overview
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Brief Summary
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Here the investigators will perform a double-blinded randomized placebo-controlled clinical trial to evaluate the synergic effect of low protein diet and prebiotics in reducing the microbial inflammatory uremic toxins.

Detailed Description
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ProLowCKD is a single-centre, double-blind, placebo-controlled, randomised study. At enrolment (T0) participants were prescribed a LPD in addition to their ongoing pharmacological therapy and according to their comorbidities; after 2 months (T2) they were randomized in accordance to a 1:1 ratio to receive probiotics or placebo for other 3 months (T5) in addition to the continuation of LPD. Enrolled subjects are invited to assume two doses of probiotic/placebo for 1 month and 1 dose for 2 months. Randomization is 1:1 to receive odd- or even envelopes, according to the odd- or even registration number at enrolment. Neither the clinician nor the patient knows the content of the odd- and even envelopes. The evaluations will be performed according to the following schedule: at T0 nephrological evaluation and biochemical analysis, dietary counselling, illustration of protocol and signing of the informed consent, administration of the SF36 questionnaire, body composition evaluation by bioimpedentiometry. At T0, T2, T5: blood biochemical parameters: haemoglobin, urea, creatinine, mean urea and creatinine clearance, CKD and MDRD calculation, sodium, potassium, uric acid, calcium, phosphate, PTH, acid-base balance, CRP, albumin, PC, IS, Lp-PLA2, LPS; 24h-urine biochemical parameters: urea, creatinine, sodium, proteins; microbial stools analysis; clinical nephrological and dietitian evaluation.

Official Title
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Probiotics-addicted Low-protein Diet for Microbiota Modulation in Patients With Advanced Chronic Kidney Disease (ProLowCKD): a Protocol of Placebo-controlled Randomized Trial

Conditions
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Renal Failure Chronic

Intervention / Treatment
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* Dietary Supplement: Probiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-80 years GFR < 20 ml/min/sqm afferent to the outpatient clinic in the Nephrology and Dialysis Unit (Azienda Ospedaliero Universitaria Maggiore della Carità) Drop out or Exclusion Criteria: subject refusing to sign the informed consent administration of prolonged antibacterial therapy dialysis initiation death

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-centre, double-blind, placebo-controlled, randomised study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotics<br>Composition: 5x109 of Bifidobacterium longum (mix DLBL), 1x109 Lactobacillus reuteri LRE02 (DSM 23878) and maltodextrin (total 2 grams) | Dietary Supplement: Probiotics<br>* Active composition: 5x109 of Bifidobacterium longum (mix DLBL), 1x 109 Lactobacillus reuteri LRE02 (DSM 23878) and maltodextrin (total 2 grams). The probiotic species employed were granted the Qualified Presumption of Safety (QPS) status by the European Food Safety Authority (EFSA) in 2007. Two envelopes per day and one envelope per day will be recommended for one and two months, respectively. Placebo composition: maltodextrin (2 grams). Two envelopes per day and one envelope per day will be recommended for one and two months, respectively.<br>|
| Placebo Comparator: Placebo<br>Composition: maltodextrin (2 grams) | Dietary Supplement: Probiotics<br>* Active composition: 5x109 of Bifidobacterium longum (mix DLBL), 1x 109 Lactobacillus reuteri LRE02 (DSM 23878) and maltodextrin (total 2 grams). The probiotic species employed were granted the Qualified Presumption of Safety (QPS) status by the European Food Safety Authority (EFSA) in 2007. Two envelopes per day and one envelope per day will be recommended for one and two months, respectively. Placebo composition: maltodextrin (2 grams). Two envelopes per day and one envelope per day will be recommended for one and two months, respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of the microbial gut populations | Change from baseline of the concentration of proteolytic microbial groups (number of cells/gram of faeces); Change from baseline of the concentration of saccharolytic microbial groups (number of cells/gram of faeces) | 5 months | 
| Change from baseline of the microbial inflammatory uremic toxins | Change from baseline of the serum concentration of PC (mcMOL) and IS (mcMOL), as markers of dysbiotic microbiota | 5 months | 
| Change from baseline of the markers of cardiovascular diseases | Change from baseline of the serum concentration of Lp-PLA2 (nmol/ml/min) | 5 months | 
| Change from baseline of the markers of intestinal barrier permeability | Change from baseline of the serum concentration of LPS (EU/ml) | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the renal function | Change from baseline of ΔGFR (mL/min/m2 of body surface) | 5 months | 
| Measurement of the urine protein excretion | Change from baseline of 24-hour protein urine excretion (mg/24 hours) | 5 months | 
| Evaluation of the anemia | Change from baseline of haemoglobin (g/dL) | 5 months | 
| Evaluation of the serum acid-base equilibrium | Change from baseline of bicarbonatemia (mEq/l) | 5 months | 
| Quantification of serum inflammatory markers | Change from baseline of the serum concentration of C-reactive protein (CRP) (mg/dL) | 5 months | 
| Evaluation of the body composition | Change from baseline of fat-free body mass (kg), fat-body mass (kg), Hand Grip strength (kg), total body water (kg) | 5 months | 
| Measurement of vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health (Quality of Life) | Change from baseline of SF36 questionnaire score. The SF36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. | 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low protein diet, Chronic kidney disease, Gut microbiota, Microbial uremic toxins, Probiotic bacteria, Intestinal dysbiosis