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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Dietary supplement: Very low protein diet supplemented with Ketosteril; Behavioral: Conventional low protein diet

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 Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• Romania
  • Bucharest, Romania, 010731
    • "Dr Carol Davila" Teaching Hospital of Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Keto-diet (KD); 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; Other Names: SVLPD, Keto-diet
ACTIVE_COMPARATOR: Low Protein Diet group (LPD); 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; Other Names: LPD; Hypoproteic diet

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance - protein intake	urinary urea nitrogen excretion to calculate the protein intake	18 months after enrolment
Compliance - energy intake	3-day food diary to calculate the daily energy intake	18 weeks after enrolment

Collaborators and Investigators

• Sponsor: Anemia Working Group Romania
• Collaborators: Dr Carol Davila Teaching Hospital of Nephrology Bucharest

Publications and helpful links

General Publications

• Mircescu G, Garneata L, Stancu SH, Capusa C. Effects of a supplemented hypoproteic diet in chronic kidney disease. J Ren Nutr. 2007 May;17(3):179-88. doi: 10.1053/j.jrn.2006.12.012.
• Hahn D, Hodson EM, Fouque D. Low protein diets for non-diabetic adults with chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 29;10(10):CD001892. doi: 10.1002/14651858.CD001892.pub5.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: January 7, 2014
• First Submitted That Met QC Criteria: January 8, 2014
• First Posted (ESTIMATE): January 9, 2014

Study Record Updates

• Last Update Posted (ACTUAL): December 22, 2017
• Last Update Submitted That Met QC Criteria: December 21, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; Nutritional status; Restricted protein diets
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: AWG13/2007