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

Phase 4

Completed

• Conditions: Chronic Kidney Disease
• Interventions: Behavioral: Conventional low protein diet; Dietary Supplement: Very low protein diet supplemented with Ketosteril

• Registration Number: NCT02031224
• Lead Sponsor: Anemia Working Group Romania

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-03
• Study First Submitted: 2014-01-07
• Study First Submitted QC: 2014-01-08
• Study First Posted: 2014-01-09
• Primary Completion: 2014-06
• Study Completion: 2014-08
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-21
• Last Update Posted: 2017-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 250

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Protein Diet group (LPD)	Conventional low protein diet	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.
Keto-diet (KD)	Very low protein diet supplemented with Ketosteril	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.

Primary Outcome Measures

Name	Time	Method
Primary composite endpoint	15 months after randomization	Need for renal replacement therapy or an at least 50% reduction in the estimated glomerular filtration rate compared to randomization

Secondary Outcome Measures

Name	Time	Method
Secondary safety parameter	18 weeks after enrolment	liver enzymes: Aspartate Aminotransferase, Alanine Transaminase
Nutritional status - biochemical marker	18 weeks after enrolment	Serum total cholesterol
Secondary safety parameter - withdrawals	18 weeks after enrolment	number of withdrawals
Inflammation	18 weeks after enrolment	serum level of C reactive protein
Safety parameter - adverse events	18 weeks after enrolment	Occurrence of any adverse event
Secondary efficacy parameter	15 weeks after randomization	variations in serum bicarbonate
Secondary outcome measure - nitrogen balance	15 months after randomization	variations in serum urea
Secondary efficacy parameter - mineral metabolism	15 weeks after randomization	variations in total serum calcium
Secondary safety parameter - anthropometric measures	18 weeks after enrolment	Mid-arm muscular circumference
Secondary outcome measure - Nutritional status	18 weeks after enrolment	Tricipital skinfold
Nutritional status - biochemical markers	18 weeks after enrolment	serum albumin

Trial Locations

Locations (1)

"Dr Carol Davila" Teaching Hospital of Nephrology; 🇷🇴 Bucharest, Romania