Renal Effects of Meditarranean Diet and Low-protein Diet With Ketoacids on Physiological Intestinal Mibrobiota in CKD

NCT02302287 | Unknown Phase 4

• 1 other identifier: rf 2013-02355394
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Food intake has a deep influence on gut microbiota composition and function, both in health and in disease status. In chronic kidney disease (CKD), a microbiota dysbiosis status is observed. Moreover, many toxic uremic molecules are microbial-derived and their accumulation promotes, in turn, disease progression. Investigators' hypothesis foresees a beneficial effect of nutritional treatments, able to restore gut microbiota balance, to lower microbial-derived uremic toxins and to improve clinical conditions in CKD patients. Mediterranean Diet (MD) is supposed to have beneficial effect on microbiota composition, while low-protein diet supplemented with ketoacids (KD) is used in CKD patients for the improvement of clinical conditions, but its effects on gut microbiota are currently unknown. Investigators' project aim is to verify the effects of MD and KD on: microbiota and metabolome composition, microbial-derived uremic toxins level and clinical conditions in a cohort of CKD patients.

Conditions

Chronic Renal Insufficiency

Keywords

Chronic kidney disease; mediterranean diet; low-protein diet; ketoacids; intestinal microbiota

Outcome Measures

Primary Outcomes (1)

• Change from baseline in fecal microbiota by MD and KD at 18 months

  Active fecal microbiota will be analyzed a culture-independent methods. Bacterial tag encoded FLX-titanium amplican pyrosequencing (bTEFAP) analyses will be carried out for bacterial RNA directly extracted from feces at months 0, 3, 9, 12 and 18.

  0-18 months from the beginning of the study

Secondary Outcomes (5)

• Change from baseline in microbial-derived uremic toxins level at 18 months

  0-18 months from the beginning of the study

• Change from baseline in renal function at 18 months

  0-18 months from the beginning of the study

• Change from baseline in nutritional status at 18 months

  0-18 months from the beginning of the study

• Change from baseline in inflammatory status at 18 months

  0-18 months from the beginning of the study

• Change from baseline in microbial-derived uremic toxins level at 18 months

  0-18 months from the beginning of the study

Study Arms (3)

Group A

EXPERIMENTAL

1. Free diet for 3 months: protein 1 g/body weight/day (animal protein 50-70 g/day, plant protein 15-20 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 1,2-1,5 g/day; sodium 6 g/day, potassium 2-4 g/day; 2. Ketoacids diet for 6 months: protein 0,3-0,5 g/bw/day (animal protein 0 g/day, plant protein 30-40 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 0,6-0,8 g/day; sodium 6 g/day, potassium 2-4 g/day; mixture of essential aminoacids and ketoacids 0,05 g/kg ideal bw/day 3. Mediterranean diet for 6 months: protein 0,7-0,8 g/bw/day (animal protein 30-40 g/day, plant protein 40-50 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 1,2-1,5 g/day; sodium 2,5-3 g/day, potassium 2-4 g/day 4. Mediterranean diet and ketoacids for 6 months

Dietary Supplement: Ketoacids diet; Other: Mediterranean diet; Other: Free diet

Group B

EXPERIMENTAL

1. Free diet for 3 months: protein 1 g/body weight/day (animal protein 50-70 g/day, plant protein 15-20 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 1,2-1,5 g/day; sodium 6 g/day, potassium 2-4 g/day; 2. Mediterranean diet for 6 months: protein 0,7-0,8 g/bw/day (animal protein 30-40 g/day, plant protein 40-50 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 1,2-1,5 g/day; sodium 2,5-3 g/day, potassium 2-4 g/day; 3. Ketoacids diet for 6 months: protein 0,3-0,5 g/bw/day (animal protein 0 g/day, plant protein 30-40 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 0,6-0,8 g/day; sodium 6 g/day, potassium 2-4 g/day; mixture of essential aminoacids and ketoacids 0,05 g/kg ideal bw/day 4. Mediterranean diet and ketoacids for 6 months

Dietary Supplement: Ketoacids diet; Other: Mediterranean diet; Other: Free diet

Group control

OTHER

Free diet: protein 1 g/body weight/day (animal protein 50-70 g/day, plant protein 15-20 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 1,2-1,5 g/day; sodium 6 g/day, potassium 2-4 g/day

Other: Free diet

Interventions

Ketoacids diet DIETARY_SUPPLEMENT

Ketoacids diet for 6 months: protein 0,3-0,5 g/bw/day (animal protein 0 g/day, plant protein 30-40 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 0,6-0,8 g/day; sodium 6 g/day, potassium 2-4 g/day; mixture of essential aminoacids and ketoacids 0,05 g/kg ideal bw/day

Also known as: KD

Group A; Group B

Mediterranean diet OTHER

Mediterranean diet for 6 months: protein 0,7-0,8 g/bw/day (animal protein 30-40 g/day, plant protein 40-50 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 1,2-1,5 g/day; sodium 2,5-3 g/day, potassium 2-4 g/day

Also known as: MD

Group A; Group B

Free diet OTHER

Free diet for 3 months: protein 1 g/body weight/day (animal protein 50-70 g/day, plant protein 15-20 g/day); energy 30-35 kcal/bw/day; Calcium 1,1-1,3 g, phosphate 1,2-1,5 g/day; sodium 6 g/day, potassium 2-4 g/day;

Also known as: FD

Group A; Group B; Group control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• prevalent patients in tertiary nephrology clinic;
• patients over 18 years;
• CKD stage 3b-4 (eGFR between 15 and 45 ml/min/1.73m2, estimated by MDRD formula);
• clinically proven adherence to prescribed therapies;
• informed consent signed.

You may not qualify if:

• change of GFR \>30% within the last 3 months;
• acute, intercurrent disease during the previous 3 months;
• severe undernutrition as indicated by: BMI \< 20 kg/m2 and serum albumin \< 3.2 g/dl, or BMI \< 17.5 kg/m2 whatever albumin value, or body weight reduction \> 5% within the last month or \> 10% within the last six months;
• pregnancy or feeding;
• chronic treatment with steroid or cytotoxic drugs; fast progressing glomerulonephritis; active SLE and vasculitis;
• gastrointestinal diseases (Crohn disease, Ulcerative colitis, Celiac Sprue, Stypsis); 7) infectious diseases; 8) cardiac failure stage III-IV NYHA; advanced liver cirrhosis; active cancer diseases; severe encephalopathy associated with lack of spontaneous feeding; chronic obstructive respiratory diseases needing oxygen treatment; 9) use of antibiotics or probiotics until 15 days before the enrolment; 10) psychiatric disease or inability to assess follow-up.

Sponsors & Collaborators

• Azienda Sanitaria ASL Avellino 2: lead

Study Sites (1)

UOC Nefrologia

Solofra, Avellino, I-83029, Italy

Location

Related Publications (8)

• Bellizzi V, Chiodini P, Cupisti A, Viola BF, Pezzotta M, De Nicola L, Minutolo R, Barsotti G, Piccoli GB, Di Iorio B. Very low-protein diet plus ketoacids in chronic kidney disease and risk of death during end-stage renal disease: a historical cohort controlled study. Nephrol Dial Transplant. 2015 Jan;30(1):71-7. doi: 10.1093/ndt/gfu251. Epub 2014 Jul 30.

  PMID: 25082793 BACKGROUND

• Bellizzi V, Di Iorio BR, De Nicola L, Minutolo R, Zamboli P, Trucillo P, Catapano F, Cristofano C, Scalfi L, Conte G; ERIKA Study-group. Very low protein diet supplemented with ketoanalogs improves blood pressure control in chronic kidney disease. Kidney Int. 2007 Feb;71(3):245-51. doi: 10.1038/sj.ki.5001955. Epub 2006 Oct 11.

  PMID: 17035939 BACKGROUND

• Marzocco S, Dal Piaz F, Di Micco L, Torraca S, Sirico ML, Tartaglia D, Autore G, Di Iorio B. Very low protein diet reduces indoxyl sulfate levels in chronic kidney disease. Blood Purif. 2013;35(1-3):196-201. doi: 10.1159/000346628. Epub 2013 Mar 13.

  PMID: 23485887 BACKGROUND

• Di Iorio BR, Bellizzi V, Bellasi A, Torraca S, D'Arrigo G, Tripepi G, Zoccali C. Phosphate attenuates the anti-proteinuric effect of very low-protein diet in CKD patients. Nephrol Dial Transplant. 2013 Mar;28(3):632-40. doi: 10.1093/ndt/gfs477. Epub 2012 Nov 19.

  PMID: 23166309 BACKGROUND

• Di Iorio BR, Minutolo R, De Nicola L, Bellizzi V, Catapano F, Iodice C, Rubino R, Conte G. Supplemented very low protein diet ameliorates responsiveness to erythropoietin in chronic renal failure. Kidney Int. 2003 Nov;64(5):1822-8. doi: 10.1046/j.1523-1755.2003.00282.x.

  PMID: 14531817 BACKGROUND

• De Angelis M, Montemurno E, Piccolo M, Vannini L, Lauriero G, Maranzano V, Gozzi G, Serrazanetti D, Dalfino G, Gobbetti M, Gesualdo L. Microbiota and metabolome associated with immunoglobulin A nephropathy (IgAN). PLoS One. 2014 Jun 12;9(6):e99006. doi: 10.1371/journal.pone.0099006. eCollection 2014.

  PMID: 24922509 BACKGROUND

• Scalone L, Borghetti F, Brunori G, Viola BF, Brancati B, Sottini L, Mantovani LG, Cancarini G. Cost-benefit analysis of supplemented very low-protein diet versus dialysis in elderly CKD5 patients. Nephrol Dial Transplant. 2010 Mar;25(3):907-13. doi: 10.1093/ndt/gfp572. Epub 2009 Dec 14.

  PMID: 20008828 BACKGROUND

• Brunori G, Viola BF, Parrinello G, De Biase V, Como G, Franco V, Garibotto G, Zubani R, Cancarini GC. Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly: a prospective randomized multicenter controlled study. Am J Kidney Dis. 2007 May;49(5):569-80. doi: 10.1053/j.ajkd.2007.02.278.

  PMID: 17472838 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Diet, Mediterranean

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Biagio Raffaele Di Iorio, PI

  Azienda Sanitaria ASL Avellino 2

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Nephrology Departement

Study Record Dates

• First Submitted: November 21, 2014
• First Posted: November 27, 2014
• Study Start: January 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: July 1, 2017
• Last Updated: November 28, 2016

Record last verified: 2016-01

Locations

IT (1)