Chronic Renal InsufficiencyPhase 4MEDIKANCT02302287
Renal Effects of Meditarranean Diet and Low-protein Diet With Ketoacids on Physiological Intestinal Mibrobiota in CKD
A Phase 4 study testing Ketoacids diet, Mediterranean diet and Free diet in people with Chronic Renal Insufficiency, run by Azienda Sanitaria ASL Avellino 2 at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Renal Insufficiency
- What is being tested?
- Ketoacids diet, Mediterranean diet and Free diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2015to Jul 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Gut-kidney Axis: Renal Effects of Meditarranean Diet and Low-protein Diet With Ketoacids to Restore Physiological Intestinal Mibrobiota in Chronic Kidney Disease
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.
Read the detailed description
Background: In CKD the biochemical milieu of gastrointestinal tract (GI) is altered by several mechanisms, affecting gut microbiota composition and function. Beyond exerting metabolic functions, microbiota influences the general healthy status. It digests food mainly through saccharolytic or proteolytic catabolism, with a prevalence of the former in healthy status. On the contrary, in CKD, dysbiosis with the prevalence of the latter is observed.
In this setting, reduction in glomerular filtration rate and increase in urea levels result in its heavy influx into the GI. Here urea is hydrolyzed spontaneously and/or by microbial urease, releasing ammonia, readily converted into ammonium hydroxide. The latter raises GI pH, causing mucosa irritation, enterocolitis and changes in microbiota composition. This contributes to worsening of inflammation and disease progression: indeed, microbiota has been identified as the primary source of several well known and yet unidentified volatile organic compounds (VOC), including some of the main uremic toxins.
Some beneficial effects observed from studies with low-protein diet supplemented with ketoacids in CKD cannot be solely explained by the reduced protein intake. Investigators' hypothesis is that ketoacids may have direct protective effects on renal damage progression, through induced modifications in gut biochemical milieu and in microbiota composition.
Similarly, the Mediterranean Diet with its fibers supply can contribute to restore gut microbiota balance.
Hypothesis:
The first hypothesis foresees a beneficial effect of KD on microbiota balancing and microbial-derived uremic toxins decrease in CKD patients, through KD-induced urea reduction. The second envisages MD direct effects on gut microbiota composition with an increase in protective species and a decrease in uremic toxins production.
The study will evaluate the effects of three different dietary regimens, composed as follows:
FD contains 1 g/bw/day of protein, plant protein 15-20 g/day;
- MD contains 0.7-0.8 g/bw/day of protein, plant protein 40-50 g/day;
- KD contains 0.3-0.5 g/bw/day of protein, animal protein zero g/day, plant protein 30-40 g/day, plus ketoacids of 0.05 g/bw/day.
Specific aim:
- To evaluate the effects of Mediterranean diet (MD) and low-protein diet supplemented with ketoacids (KD) on microbiota composition
- To evaluate the effects of KD and MD on microbial-derived VOC (already identified and yet unidentified uremic toxins) levels by metabolomics
- To evaluate the effects of KD or MD on renal function parameters, uremia, inflammatory and nutritional status
Experimental Design Aim 1:
The designed study will be experimental, randomized, cross-over. It will be carried out according to the Declaration of Helsinki (IV Adaptation) and will be submitted to the approval of the local Ethics Committee; written consent will be obtained from all subjects. 60 patients with CKD stages 3b-4 (MDRD formula) will be enrolled, according to the inclusion and exclusion criteria (see below).
Experimental Design Aim 2:
Untarget metabolomic analysis will be carried out on fecal and urine samples collected at the same time points described in Experimental design aim 1 for VOC (GC-MS/MS) and non-VOC profiling (LC-MS/MS). Sera collected at the same time points will be also analyzed by untarget metabolomic for non-VOC profiling and by target metabolomic to quantify the already known uremic toxins, namely indoxyl sulfate and p-cresyl sulfate, and potential metabolite biomarkers found by the untarget experiment.
Experimental Design Aim 3:
Additionally, each patient will undergo medical examination every three months, with evaluation of: blood pressure and nutritional status. Moreover, at the same time points of aim 1 (T0, T3, T9, T12 and T18 months from the beginning of the study) each patient will provide blood and urine samples, both for routine and experimental analysis.
- Conditions
- Chronic Renal Insufficiency
- Being tested
- Ketoacids diet, Mediterranean diet, Free diet
- Keywords
- Chronic kidney disease, mediterranean diet, low-protein diet, ketoacids, intestinal microbiota
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketoacids dietDietary supplement
Also called KD
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
Mediterranean dietOther
Also called MD
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
Free dietOther
Also called FD
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;
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Other: Free diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0-18 months from the beginning of the study
Secondary outcomes (5)
Change from baseline in microbial-derived uremic toxins level at 18 months
Untarget metabolomic analysis will be carried out on fecal and urine samples collected at months 0,3,9,12 and 18 after the beginning of the study for volatile organic compounds (VOC) (GC-MS/MS) and non-VOC profiling (LC-MS/MS). Sera collected at the same time points will be also analyzed by untarget metabolomic for non-VOC profiling and by target matabolomic to quantify uremic toxins, as indoxyl sulfate and p-cresyl sulfate, and potential metabolite biomarkers found by the untarget experiment
Measured: 0-18 months from the beginning of the study
Change from baseline in renal function at 18 months
each patient will provide at months 0,3,9,12 and 18 blood and urine samples for routine analyses to measure urea, creatinine, estimated glomerular filtration rate, BUN, blood pressure, proteinuria
Measured: 0-18 months from the beginning of the study
Change from baseline in nutritional status at 18 months
each patient will provide at months 0,3,9,12 and 18 blood and urine samples for routine analyses to measure acid-basic balance, serum and urine electrolytes, PTH, serum proteins, haemoglobin,
Measured: 0-18 months from the beginning of the study
Change from baseline in inflammatory status at 18 months
each patient will provide at months 0,3,9,12 and 18 blood and urine samples for routine analyses to measure EGF/MCP-1 ratio, CRP, TNF-a, IL-6
Measured: 0-18 months from the beginning of the study
Change from baseline in microbial-derived uremic toxins level at 18 months
Sera will be collected at months 0,3,9,12 and 18 after the beginning of the study to quantify uremic toxin Cyanate
Measured: 0-18 months from the beginning of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2014 (estimated)
- Study startJan 2015
- Primary completionJan 2017 (estimated)
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Chronic Renal InsufficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Sanitaria ASL Avellino 2
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Biagio Di Iorio, Azienda Sanitaria ASL Avellino 2
- Investigators
- Biagio Raffaele Di Iorio, PI, Principal investigator, Azienda Sanitaria ASL Avellino 2
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02302287
- Sponsor's protocol ID
- rf 2013-02355394
- Acronym
- MEDIKA
- Status last verified
- Jan 2016
- First submitted
- 21 Nov 2014
- Last updated
- 28 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25082793Bellizzi 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.
PubMed 17035939Marzocco 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.
PubMed 23485887Di 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.
PubMed 23166309Di 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.
PubMed 14531817De 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.
PubMed 24922509Scalone 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.
PubMed 20008828Brunori 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.
PubMed 17472838
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut-kidney Axis: Renal Effects of Meditarranean Diet and Low-protein Diet With Ketoacids to Restore Physiological Intestinal Mibrobiota in Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT02302287
- Acronym / sponsor ID
- MEDIKA / rf 2013-02355394
- Conditions
- Chronic Renal Insufficiency
- Keywords
- Chronic kidney disease, mediterranean diet, low-protein diet, ketoacids, intestinal microbiota
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Azienda Sanitaria ASL Avellino 2University, hospital or other
- Study start
- Jan 2015
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Jul 2017 (estimated)
- First posted
- 27 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background: In CKD the biochemical milieu of gastrointestinal tract (GI) is altered by several mechanisms, affecting gut microbiota composition and function. Beyond exerting metabolic functions, microbiota influences the general healthy status. It digests food mainly through saccharolytic or proteolytic catabolism, with a prevalence of the former in healthy status. On the contrary, in CKD, dysbiosis with the prevalence of the latter is observed.
In this setting, reduction in glomerular filtration rate and increase in urea levels result in its heavy influx into the GI. Here urea is hydrolyzed spontaneously and/or by microbial urease, releasing ammonia, readily converted into ammonium hydroxide. The latter raises GI pH, causing mucosa irritation, enterocolitis and changes in microbiota composition. This contributes to worsening of inflammation and disease progression: indeed, microbiota has been identified as the primary source of several well known and yet unidentified volatile organic compounds (VOC), including some of the main uremic toxins.
Some beneficial effects observed from studies with low-protein diet supplemented with ketoacids in CKD cannot be solely explained by the reduced protein intake. Investigators' hypothesis is that ketoacids may have direct protective effects on renal damage progression, through induced modifications in gut biochemical milieu and in microbiota composition.
Similarly, the Mediterranean Diet with its fibers supply can contribute to restore gut microbiota balance.
Hypothesis:
The first hypothesis foresees a beneficial effect of KD on microbiota balancing and microbial-derived uremic toxins decrease in CKD patients, through KD-induced urea reduction. The second envisages MD direct effects on gut microbiota composition with an increase in protective species and a decrease in uremic toxins production.
The study will evaluate the effects of three different dietary regimens, composed as follows:
FD contains 1 g/bw/day of protein, plant protein 15-20 g/day;
- MD contains 0.7-0.8 g/bw/day of protein, plant protein 40-50 g/day;
- KD contains 0.3-0.5 g/bw/day of protein, animal protein zero g/day, plant protein 30-40 g/day, plus ketoacids of 0.05 g/bw/day.
Specific aim:
- To evaluate the effects of Mediterranean diet (MD) and low-protein diet supplemented with ketoacids (KD) on microbiota composition
- To evaluate the effects of KD and MD on microbial-derived VOC (already identified and yet unidentified uremic toxins) levels by metabolomics
- To evaluate the effects of KD or MD on renal function parameters, uremia, inflammatory and nutritional status
Experimental Design Aim 1:
The designed study will be experimental, randomized, cross-over. It will be carried out according to the Declaration of Helsinki (IV Adaptation) and will be submitted to the approval of the local Ethics Committee; written consent will be obtained from all subjects. 60 patients with CKD stages 3b-4 (MDRD formula) will be enrolled, according to the inclusion and exclusion criteria (see below).
Experimental Design Aim 2:
Untarget metabolomic analysis will be carried out on fecal and urine samples collected at the same time points described in Experimental design aim 1 for VOC (GC-MS/MS) and non-VOC profiling (LC-MS/MS). Sera collected at the same time points will be also analyzed by untarget metabolomic for non-VOC profiling and by target metabolomic to quantify the already known uremic toxins, namely indoxyl sulfate and p-cresyl sulfate, and potential metabolite biomarkers found by the untarget experiment.
Experimental Design Aim 3:
Additionally, each patient will undergo medical examination every three months, with evaluation of: blood pressure and nutritional status. Moreover, at the same time points of aim 1 (T0, T3, T9, T12 and T18 months from the beginning of the study) each patient will provide blood and urine samples, both for routine and experimental analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Dietary Supplement: Ketoacids diet, Other: Mediterranean diet, Other: Free diet1. 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 |
| Group B | Experimental | Dietary Supplement: Ketoacids diet, Other: Mediterranean diet, Other: Free diet1. 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 |
| Group control | Other | Other: Free dietFree 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketoacids dietAlso: KDKetoacids 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 | Dietary supplement | Group A, Group B |
| Mediterranean dietAlso: MDMediterranean 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 | Other | Group A, Group B |
| Free dietAlso: FDFree 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; | Other | Group A, Group B, Group control |
Primary outcome
Change from baseline in fecal microbiota by MD and KD at 18 months
Time frame: 0-18 months from the beginning of the study
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.
5 secondary outcomes
Change from baseline in microbial-derived uremic toxins level at 18 months
Time frame: 0-18 months from the beginning of the study
Change from baseline in renal function at 18 months
Time frame: 0-18 months from the beginning of the study
Change from baseline in nutritional status at 18 months
Time frame: 0-18 months from the beginning of the study
Change from baseline in inflammatory status at 18 months
Time frame: 0-18 months from the beginning of the study
Change from baseline in microbial-derived uremic toxins level at 18 months
Time frame: 0-18 months from the beginning of the study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2016.
- Background: PubMed 25082793Bellizzi 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.
- Background: PubMed 17035939Bellizzi 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.
- Background: PubMed 23485887Marzocco 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.
- Background: PubMed 23166309Di 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.
- Background: PubMed 14531817Di 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.
- Background: PubMed 24922509De 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.
- Background: PubMed 20008828Scalone 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.
- Background: PubMed 17472838Brunori 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Biagio Raffaele Di Iorio, PI principal investigator
Azienda Sanitaria ASL Avellino 2
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketoacids diet, Mediterranean diet and Free diet in people with Chronic Renal Insufficiency, run by Azienda Sanitaria ASL Avellino 2 at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in fecal microbiota by MD and KD at 18 months (time frame: 0-18 months from the beginning of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02302287, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2016.