Could Ketoanalogue-supplemented Low Protein Diet Defer Dialysis in Advanced Diabetic Kidney Disease? (K-DDD)

CKD Stage 4 Clinical Trial

— K-DDD  

Official title:

Ketoanalogue-supplemented Low Protein Diet and Deferring Dialysis in Patients With Severe Proteinuria and Advanced Diabetic Kidney Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03415074
• Other study ID #: AnemiaWGRomania
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2019
• Est. completion date: March 31, 2023

Study information

• Verified date: February 2020
• Source: Anemia Working Group Romania
• Contact: Liliana Garneata, Assoc Prof
• Phone: +40722619358
• Email: lilianagarna[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective single center open label randomized controlled trial aiming to assess the effectiveness and safety of a low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (sLPD) as compared to a mild protein restriction (0.8 g/kg-day, MPD) in reducing Chronic Kidney Disease (CKD) progression, with a planned total duration is of 18 months.

Adult diabetic patients with CKD stage 4+ [estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease 4-variable (MDRD4) formula <30 mL/min per year], with stable renal function (historical reduction of eGFR of < 10 ml/min-year) , proteinuria > 3g/g creatininuria and good nutritional status (SGA A) will be enrolled.

Description:

Adult diabetic patients with Chronic Kidney Disease (CKD) stage 4+ (estimated GFR using the Modification of Diet in Renal Disease 4-variable, MDRD4, formula <30 mL/min per year), with stable renal function (historical reduction of eGFR of < 10 ml/min-year), proteinuria > 3g/g creatininuria and good nutritional status (SGA A) will be enrolled. Patients with evidence of active kidney disease (except proteinuria), with indication of etiological or pathogenic treatment, those with poor control of diabetes (HbA1c >8%), those with uncontrolled high blood pressure (≥155/85 mmHg), those with significant co-morbidities (heart failure, active liver disease, malabsorption, active infections, inflammatory diseases requiring corticosteroids), those with uremic symptoms (pericarditis, digestive disorders ) or malnutrition (SGA B or C, serum albumin < 3.5 g/dl) will be excluded.

Eligible patients will enter a run-in phase (3 mo), when mild protein restriction (0.8g/kg dry ideal bw) will be initiated and compliance will be evaluated twice monthly.

Those who will prove compliant during the run-in phase and still fulfill the selection criteria will be randomized 1:1 (computer-generated numbers) to receive the low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (Ketosteril 1 tb/10 kg dry bw) or to continue the mild protein restriction (0.8 g/kg-day).

The total recommended energy intake is of 30 kcal/kg of ideal dry body weight per day in all patients.

The primary composite endpoint is the need for RRT initiation or a more than 50% reduction in the initial eGFR any time during the assessment phase. The decision to initiate RRT will be made by the Ethical Committee of the Hospital, based on the clinical and laboratory data.

The need for RRT initiation, the quality of life [assessed by the Short Form-36 (SF-36) Questionnaire], the decline in GFR and the correction of metabolic complications of CKD [serum levels of urea, calcium, phosphates, serum parathyroid hormone levels, bicarbonate, potassium] will be secondary efficacy parameters.

Parameters of nutritional status (SGA, anthropometric and biochemical parameters), compliance to the diet, occurrence of any adverse event and the number of withdrawals will be safety variables.

All the parameters will be assessed at baseline, throughout the intervention phase and at end of the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 31, 2023
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• diabetic patients

• CKD stage 4+ (estimated GFR using the Modification of Diet in Renal Disease 4-variable, MDRD4, formula <30 mL/min per year)

• stable renal function (historical reduction of eGFR of < 10 ml/min-year)

• proteinuria > 3g/g creatininuria

• good nutritional status (SGA A)

Exclusion Criteria:

• evidence of active kidney disease (except proteinuria)

• indication for etiological or pathogenic treatment

• poor control of diabetes (HbA1c >8%)

• uncontrolled high blood pressure (=155/85 mmHg)

• significant co-morbidities (heart failure, active liver disease, malabsorption, active infections, inflammatory diseases requiring corticosteroids)

• uremic symptoms (pericarditis, digestive disorders

• or malnutrition (SGA B or C, serum albumin < 3.5 g/dl)

Related Conditions & MeSH terms

• CKD Stage 4
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Behavioral:
• Protein restriction
In both arms the dietary protein intake will be reduced. In the sLPD arm, the protein restriction is more severe and ketoanalogues of the essential aminoacids are offered.

Locations

Country	Name	City	State
Romania	"Dr Carol Davila" Teaching Hospital of Nephrology	Bucharest

Sponsors (1)

Lead Sponsor	Collaborator
Anemia Working Group Romania

Country where clinical trial is conducted

Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CKD progression	Percentage of patients requiring RRT initiation or a more than 50% reduction in the initial eGFR at anytime during the study	15 months
Secondary	Need for renal replacement therapy (RRT)	Percentage of patients requiring RRT during the study	15 months
Secondary	Patients' Quality of life	Patients' Quality of life, assessed by the SF-36 Questionnaire	at baseline and than every 3 months up to 15 months
Secondary	Decline in eGFR	Difference between eGFR at any timepoint and the initial eGFR	monthly up to 15 months
Secondary	Correction of nitrogen balance	Serum urea	monthly up to 15 months
Secondary	Correction of metabolic acidosis	Serum bicarbonate	monthly up to 15 months
Secondary	Correction of calcium metabolism abnormalities	Serum calcium	monthly up to 15 months
Secondary	Correction of mineral metabolism abnormalities	Serum phosphates	monthly up to 15 months
Secondary	Serum level of intact Parathyroid Hormone (iPTH)	iPTH	monthly up to 15 months
Secondary	Nutritional status - Subjective Global Assessment (SGA)	SGA	monthly up to 15 months
Secondary	Body Mass Index (BMI)	BMI	monthly up to 15 months
Secondary	Tricipital Skin Fold (TSF)	TSF	monthly up to 15 months
Secondary	Middle arm muscular circumference (MAMC)	MAMC	monthly up to 15 months
Secondary	Serum albumin	Serum albumin	monthly up to 15 months
Secondary	Serum cholesterol	Serum cholesterol	monthly up to 15 months
Secondary	Inflammatory status	Serum C-Reactive Protein (CRP)	monthly up to 15 months
Secondary	Compliance to the protein intake	Achieved protein intake (urinary urea excretion, Mitch-Maroni's formula)	twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and then every 3 months up to 15 months
Secondary	Compliance to the energy intake	Achieved energy intake (3-days food dairy)	twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and then every 3 months up to 15 months
Secondary	Occurence of the adverse events	Occurence of any adverse event	twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and every 3 months up to 15 months