Clinical trial NCT04204005: Probiotics and Low Protein Diet in Advanced Chronic Kidney Disease
Official title: Probiotics-addicted Low-protein Diet for Microbiota Modulation in Patients With Advanced Chronic Kidney Disease (ProLowCKD): a Protocol of Placebo-controlled Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Renal Failure Chronic
Keywords: Low protein diet
Chronic kidney disease
Gut microbiota
Microbial uremic toxins
Probiotic bacteria
Intestinal dysbiosis
Lead sponsor: Probiotical S.p.A.
Sponsor class: INDUSTRY
Collaborators: name: Azienda Ospedaliero Universitaria Maggiore della Carita
First posted: 2019-12-18
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-centre, double-blind, placebo-controlled, randomised study.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline of the microbial gut populations
timeFrame: 5 months
measure: Change from baseline of the microbial inflammatory uremic toxins
timeFrame: 5 months
measure: Change from baseline of the markers of cardiovascular diseases
timeFrame: 5 months
measure: Change from baseline of the markers of intestinal barrier permeability
timeFrame: 5 months
Secondary outcomes:
measure: Evaluation of the renal function
timeFrame: 5 months
measure: Measurement of the urine protein excretion
timeFrame: 5 months
measure: Evaluation of the anemia
timeFrame: 5 months
measure: Evaluation of the serum acid-base equilibrium
timeFrame: 5 months
measure: Quantification of serum inflammatory markers
timeFrame: 5 months
measure: Evaluation of the body composition
timeFrame: 5 months
measure: 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)
timeFrame: 5 months
Other outcomes:
Locations:
city: Novara
country: Italy
facility: Nephrology and Dialysis Unit, Azienda Ospedaliero Universitaria Maggiore della Carità
Study officials:
affiliation: Azienda Ospedaliero Universitaria Maggiore della Carità
name: Andreana De Mauri
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold G, Quraishi MN, Kinross J, Smidt H, Tuohy KM, Thomas LV, Zoetendal EG, Hart A. The gut microbiota and host health: a new clinical frontier. Gut. 2016 Feb;65(2):330-9. doi: 10.1136/gutjnl-2015-309990. Epub 2015 Sep 2.
citation: 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.
citation: Mafra D, Fouque D. Gut microbiota and inflammation in chronic kidney disease patients. Clin Kidney J. 2015 Jun;8(3):332-4. doi: 10.1093/ckj/sfv026. Epub 2015 May 6.
citation: Mafra D, Lobo JC, Barros AF, Koppe L, Vaziri ND, Fouque D. Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol. 2014;9(3):399-410. doi: 10.2217/fmb.13.165.
citation: Rossi M, Klein K, Johnson DW, Campbell KL. Pre-, pro-, and synbiotics: do they have a role in reducing uremic toxins? A systematic review and meta-analysis. Int J Nephrol. 2012;2012:673631. doi: 10.1155/2012/673631. Epub 2012 Dec 19.
citation: Vaziri ND. Effect of Synbiotic Therapy on Gut-Derived Uremic Toxins and the Intestinal Microbiome in Patients with CKD. Clin J Am Soc Nephrol. 2016 Feb 5;11(2):199-201. doi: 10.2215/CJN.13631215. Epub 2016 Jan 15. No abstract available.