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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03415074
Recruitment Status : Recruiting
First Posted : January 30, 2018
Last Update Posted : February 24, 2020
Sponsor:
Information provided by (Responsible Party):
Anemia Working Group Romania

Brief 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.


Condition or disease Intervention/treatment Phase
CKD Stage 4 Behavioral: Protein restriction Not Applicable

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Eligible patients will enter a run-in phase (3 mo), when mild protein diet (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).

Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Ketoanalogue-supplemented Low Protein Diet and Deferring Dialysis in Patients With Severe Proteinuria and Advanced Diabetic Kidney Disease
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Supplemented low protein diet (sLPD)
Protein restriction to a low level (0.6 g/kg-day, mainly vegetarian) + ketoanalogues of essential amino-acids supplementation (Ketosteril 1 tb/10 kg dry bw)
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.

Active Comparator: Mild protein restriction diet (MPD)
Mild restriction in dietary protein intake (0.8 g/kg-day)
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.




Primary Outcome Measures :
  1. CKD progression [ Time Frame: 15 months ]
    Percentage of patients requiring RRT initiation or a more than 50% reduction in the initial eGFR at anytime during the study


Secondary Outcome Measures :
  1. Need for renal replacement therapy (RRT) [ Time Frame: 15 months ]
    Percentage of patients requiring RRT during the study

  2. Patients' Quality of life [ Time Frame: at baseline and than every 3 months up to 15 months ]
    Patients' Quality of life, assessed by the SF-36 Questionnaire

  3. Decline in eGFR [ Time Frame: monthly up to 15 months ]
    Difference between eGFR at any timepoint and the initial eGFR

  4. Correction of nitrogen balance [ Time Frame: monthly up to 15 months ]
    Serum urea

  5. Correction of metabolic acidosis [ Time Frame: monthly up to 15 months ]
    Serum bicarbonate

  6. Correction of calcium metabolism abnormalities [ Time Frame: monthly up to 15 months ]
    Serum calcium

  7. Correction of mineral metabolism abnormalities [ Time Frame: monthly up to 15 months ]
    Serum phosphates

  8. Serum level of intact Parathyroid Hormone (iPTH) [ Time Frame: monthly up to 15 months ]
    iPTH

  9. Nutritional status - Subjective Global Assessment (SGA) [ Time Frame: monthly up to 15 months ]
    SGA

  10. Body Mass Index (BMI) [ Time Frame: monthly up to 15 months ]
    BMI

  11. Tricipital Skin Fold (TSF) [ Time Frame: monthly up to 15 months ]
    TSF

  12. Middle arm muscular circumference (MAMC) [ Time Frame: monthly up to 15 months ]
    MAMC

  13. Serum albumin [ Time Frame: monthly up to 15 months ]
    Serum albumin

  14. Serum cholesterol [ Time Frame: monthly up to 15 months ]
    Serum cholesterol

  15. Inflammatory status [ Time Frame: monthly up to 15 months ]
    Serum C-Reactive Protein (CRP)

  16. Compliance to the protein intake [ Time Frame: 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 ]
    Achieved protein intake (urinary urea excretion, Mitch-Maroni's formula)

  17. Compliance to the energy intake [ Time Frame: 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 ]
    Achieved energy intake (3-days food dairy)

  18. Occurence of the adverse events [ Time Frame: 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 ]
    Occurence of any adverse event



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03415074


Contacts
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Contact: Liliana Garneata, Assoc Prof +40722619358 lilianagarna@yahoo.com
Contact: Gabriel Stefan, MD +40724906188 gabriel_stefan@rocketmail.com

Locations
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Romania
"Dr Carol Davila" Teaching Hospital of Nephrology Recruiting
Bucharest, Romania, 010731
Contact: Liliana Garneata, Assoc Prof    +40722619358    lilianagarna@yahoo.com   
Contact: Carmen Antonia Mocanu, MD    +40723673275    carmen_a9@yahoo.com   
Sponsors and Collaborators
Anemia Working Group Romania
Investigators
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Study Chair: Gabriel Mircescu, Prof Carol Davila University of Medicine and Pharmacy
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Anemia Working Group Romania
ClinicalTrials.gov Identifier: NCT03415074    
Other Study ID Numbers: AnemiaWGRomania
First Posted: January 30, 2018    Key Record Dates
Last Update Posted: February 24, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Unique patient number in the study, biological data; no data to enable patient identification will be provided
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: March 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Anemia Working Group Romania:
low protein diet
Diabetic Kidney Disease
Additional relevant MeSH terms:
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Kidney Diseases
Diabetic Nephropathies
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases