Supplemented Very Low Protein Diet and the Progression of Chronic Kidney Disease

Study Overview
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Brief Summary
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This is a prospective single center randomized controlled trial with a total duration of 18 months aiming to evaluate the effectiveness and the safety of a very low protein diet supplemented with ketoanalogues of essential aminoacids in reducing the progression of chronic kidney disease (CKD) in patients with advanced CKD.

Detailed Description
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All eligible patients who will give informed consent will be screened. Those meeting the selection criteria will be enrolled and will enter a 3-month run-in phase during which a conventional LPD will be prescribed in all patients. At the end of this phase, the subjects still fulfilling all the selection criteria will be randomized in a 1:1 ratio to receive the KD or to continue the conventional LPD for a total duration of 15 months. Nineteen blood and urine samplings are scheduled for each patient, to be drawn monthly. The laboratory reports include the nitrogen compounds, calcium-phosphorus metabolism parameters, acid-base balance, biochemical nutritional markers, serum C-reactive protein, hemoglobin, blood cell count, and biochemical safety parameters (sodium, potassium, liver enzymes, and bilirubin). The anthropometric measurements and subjective global assessment will be evaluated at enrolment, at randomization, and every 3 months thereafter. The compliance with the prescribed diet (protein and energy intake) will be assessed monthly during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and every 3 months thereafter. The blood pressure levels, drugs required for the therapy of hypertension, acidosis and mineral metabolism disorders, and occurrence of adverse events will be recorded monthly.

Official Title
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Effect of Very Low Protein Diet Supplemented With Ketoanalogues of the Essential Amino Acids on the Progression of Chronic Kidney Disease

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Behavioral: Conventional low protein diet
* Dietary Supplement: Very low protein diet supplemented with Ketosteril


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult non-diabetic patients stage 4-5 CKD not on dialysis (estimated glomerular filtration by Modification of Diet in Renal Disease formula < 30 mL/min per year stable renal function at least 12 weeks before enrollment well-controlled arterial blood pressure proteinuria less than 1 g/g urinary creatinine good nutritional status declared and anticipated good compliance with the prescribed diet Exclusion Criteria: poorly controlled arterial blood pressure (≥145/85 mm Hg) relevant comorbid conditions (diabetes mellitus, heart failure, active hepatic disease, digestive diseases with malabsorption, inflammation/anti-inflammatory therapy) uremic complications (pericarditis, polyneuropathy) feeding inability (anorexia, nausea)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Keto-diet (KD)<br>Patients in the intervention arm (KD group) will receive a vegetarian very low protein diet (0.3 g proteins/kg ideal body weight per day) supplemented with ketoanalogues of essential amino acids (Ketosteril®, Fresenius Kabi, Bad Homburg, Germany), 1 capsule for every 5 kg of ideal dry body weight per day. | Dietary Supplement: Very low protein diet supplemented with Ketosteril<br> <br> * Other names: SVLPD, Keto-diet;|
| Active Comparator: Low Protein Diet group (LPD)<br>The patients in the control arm (LPD group) will continue their conventional low protein diet, with 0.6 g/kg per day (including high biological value proteins). The total recommended energy intake is of 30 kcal/kg of ideal dry body weight per day in both arms. | Behavioral: Conventional low protein diet<br> <br> * Other names: Hypoproteic diet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary composite endpoint | Need for renal replacement therapy or an at least 50% reduction in the estimated glomerular filtration rate compared to randomization | 15 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary efficacy parameter | The rate of decline in the estimated Glomerular Filtration Rate | months 3-15 after randomization | 
| Secondary outcome measure - nitrogen balance | variations in serum urea | 15 months after randomization | 
| Secondary efficacy parameter - mineral metabolism | variations in total serum calcium | 15 weeks after randomization | 
| Secondary efficacy parameter | variations in serum phosphate level | 15 weeks after randomization | 
| Secondary efficacy parameter | variations in serum bicarbonate | 15 weeks after randomization | 
| Secondary safety parameter | Subjective Global Assessment of the nutritional status | 18 weeks after enrolment | 
| Secondary safety parameter | Body Mass Index | 18 weeks after enrolment | 
| Secondary outcome measure - Nutritional status | Tricipital skinfold | 18 weeks after enrolment | 
| Secondary safety parameter - anthropometric measures | Mid-arm muscular circumference | 18 weeks after enrolment | 
| Nutritional status - biochemical markers | serum albumin | 18 weeks after enrolment | 
| Inflammation | serum level of C reactive protein | 18 weeks after enrolment | 
| Nutritional status - biochemical marker | Serum total cholesterol | 18 weeks after enrolment | 
| Secondary safety parameter | Serum potassium level | 18 weeks after enrolment | 
| Secondary safety parameter | liver enzymes: Aspartate Aminotransferase, Alanine Transaminase | 18 weeks after enrolment | 
| Safety parameter - adverse events | Occurrence of any adverse event | 18 weeks after enrolment | 
| Secondary safety parameter - withdrawals | number of withdrawals | 18 weeks after enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease, Restricted protein diets, Nutritional status