Probiotics and Low Protein Diet in Advanced Chronic Kidney Disease

Renal Failure Chronic Clinical Trial

— ProLowCKD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04204005
• Other study ID #: 215/CE n.CE 30\17
• Status: Completed
• Phase: N/A
• Start date: March 13, 2017
• Est. completion date: December 31, 2020

Study information

• Verified date: December 2019
• Source: Probiotical S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Diseases
• Kidney Failure, Chronic
• Renal Failure Chronic
• Renal Insufficiency, Chronic

Intervention

Dietary Supplement:
• Probiotics
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.

Locations

Country	Name	City	State
Italy	Nephrology and Dialysis Unit, Azienda Ospedaliero Universitaria Maggiore della Carità	Novara

Sponsors (2)

Lead Sponsor	Collaborator
Probiotical S.p.A.	Azienda Ospedaliero Universitaria Maggiore della Carita

Country where clinical trial is conducted

Italy, 

References & Publications (6)

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. — View 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. Review. — View 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. Review. — View 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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Change from baseline of the markers of cardiovascular diseases	Change from baseline of the serum concentration of Lp-PLA2 (nmol/ml/min)	5 months
Primary	Change from baseline of the markers of intestinal barrier permeability	Change from baseline of the serum concentration of LPS (EU/ml)	5 months
Secondary	Evaluation of the renal function	Change from baseline of ?GFR (mL/min/m2 of body surface)	5 months
Secondary	Measurement of the urine protein excretion	Change from baseline of 24-hour protein urine excretion (mg/24 hours)	5 months
Secondary	Evaluation of the anemia	Change from baseline of haemoglobin (g/dL)	5 months
Secondary	Evaluation of the serum acid-base equilibrium	Change from baseline of bicarbonatemia (mEq/l)	5 months
Secondary	Quantification of serum inflammatory markers	Change from baseline of the serum concentration of C-reactive protein (CRP) (mg/dL)	5 months
Secondary	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
Secondary	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