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Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis Chronic Kidney Disease (CKD) Patients (CKD)

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ClinicalTrials.gov Identifier: NCT03077048
Recruitment Status : Completed
First Posted : March 10, 2017
Last Update Posted : May 14, 2018
EastHORN Clinical Services in CEE
MLM Medical Labs GmbH
ALS Czech Republic, s.r.o.
PCG Clinical Services AB
Information provided by (Responsible Party):
Fresenius Kabi

Brief Summary:

Supplementation of ketoanalogues of essential amino acids improves the protein quality of protein restricted diets without burdening the kidneys. The ketoanalogues are transaminated by aminotransferases to the corresponding amino acids by incorporating nitrogen from amino groups derived from endogenous amino acid degradation. Therefore, less nitrogen needs to be excreted and the kidney's workload is reduced.

The purpose of the trial is to investigate the impact of Ketosteril® supplementation on A) nutritional safety and tolerance of a low protein diet (LPD) (0.6 g protein/kg bodyweight (BW)/day)and B) net protein synthesis in pre-dialysis CKD patients.

Changes of urea in serum and urine will be assessed under controlled metabolic balance conditions in non-dialysed CKD patients consuming a LPD supplemented with Ketosteril® at 1 tablet/5 kg body weight/day compared to the same, isonitrogenous and isocaloric diet without Ketosteril®.

Changes in protein synthesis and degradation at the defined protein intake with or without Ketosteril® supplementation will be investigated - based on nitrogen balance, normalized protein catabolic rates as well as blood levels of defined proteins as surrogate markers for net protein synthesis and anabolic signaling.

Condition or disease Intervention/treatment Phase
Renal Insufficiency, Chronic Drug: Ketosteril® Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis CKD Patients - A Randomized, Controlled, Open-labelled Clinical Trial
Actual Study Start Date : March 30, 2017
Actual Primary Completion Date : April 27, 2018
Actual Study Completion Date : May 2, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
No Intervention: Low protein diet
Low protein diet with 0.6 g protein/kg BW/day (20-30% high biological value) and an energy intake of 30-35 kcal/kg BW/day
Experimental: Supplemented low protein diet
Ketosteril® supplemented low protein diet (sLPD), (1 tablet/5 kg BW/day) with 0.6 g protein/kg BW/day (20-30% high biological value) and an energy intake of 30-35 kcal/kg BW/day
Drug: Ketosteril®
Patients will be randomised to receive isonitrogenous and isocaloric LPD providing 0.6 g protein/kg BW/day and an energy intake of 30-35 kcal/kg BW/day with (test group) or without (control group) intake of Ketosteril® (1 tablet/5 kg BW/day). The control group will get additional food protein to balance the nitrogen content of Ketosteril® The mainly vegetarian diet will be maintained for 10 days.
Other Name: EV product code: PRD1170237

Primary Outcome Measures :
  1. Impact of Ketosteril® on the generation of nitrogenous waste products [ Time Frame: 10 days ]
    Serum urea

  2. Impact of Ketosteril® on the generation of nitrogenous waste products [ Time Frame: 10 days ]
    Urine urea

  3. Impact of Ketosteril® on the generation of nitrogenous waste products [ Time Frame: 10 days ]
    Nitrogen balance

  4. Impact of Ketosteril® on the generation of nitrogenous waste products [ Time Frame: 10 days ]
    Normalized protein catabolic rate (nPCR)

  5. Protein metabolism [ Time Frame: 10 days ]
    Serum total proteins

  6. Protein metabolism [ Time Frame: 10 days ]

  7. Protein metabolism [ Time Frame: 10 days ]

  8. Protein metabolism [ Time Frame: 10 days ]

  9. Markers of anabolic signaling [ Time Frame: 10 days ]
    Serum Insulin-like growth factor (IGF)-I

  10. Markers of anabolic signaling [ Time Frame: 10 days ]
    Insulin like growth factor (IGF)-II

  11. Markers of anabolic signaling [ Time Frame: 10 days ]
    IGF-binding protein 3

Secondary Outcome Measures :
  1. Renal function [ Time Frame: 10 days ]

  2. Renal function [ Time Frame: 10 days ]

  3. Renal function [ Time Frame: 10 days ]
    Serum and urine creatinine

  4. Renal function [ Time Frame: 10 days ]
    Serum and urine urea

  5. Renal function [ Time Frame: 10 days ]
    Serum urea nitrogen (SUN)

  6. Renal function [ Time Frame: 10 days ]
    Urine nitrogen

  7. Renal function [ Time Frame: 10 days ]
    Glomerular filtration rate estimated from serum creatinine (eGFR)

  8. Renal function [ Time Frame: 10 days ]
    Albumin-creatinine ratio

  9. Renal function [ Time Frame: 10 days ]
    Urea clearance

  10. Nutritional status [ Time Frame: 10 days ]
    Body weight

  11. Nutritional status [ Time Frame: 10 days ]
    Body Mass Index (BMI)

  12. Nutritional status [ Time Frame: 10 days ]
    Body composition (via Bio Impedance Spectroscopy)

  13. Nutritional status [ Time Frame: 10 days ]
    SUN-to-creatinine ratio

  14. Glucose metabolism [ Time Frame: 10 days ]
    Fasting blood glucose

  15. Lipid profile [ Time Frame: 10 days ]

  16. Lipid profile [ Time Frame: 10 days ]

  17. Lipid profile [ Time Frame: 10 days ]
    High-density lipoprotein (HDL)/Low-density lipoprotein (LDL)-cholesterol

  18. Mineral status [ Time Frame: 10 days ]

  19. Mineral status [ Time Frame: 10 days ]

  20. Mineral status [ Time Frame: 10 days ]

  21. Mineral status [ Time Frame: 10 days ]

  22. Mineral status [ Time Frame: 10 days ]
    Phosphate (serum and urine)

  23. Mineral status [ Time Frame: 10 days ]
    Alkaline phosphatase

  24. Mineral status [ Time Frame: 10 days ]
    Fibroblast growth factor (FGF)-23

  25. Mineral status [ Time Frame: 10 days ]
    25-hydroxycholecalciferol (serum)

  26. Acid-base balance [ Time Frame: 10 days ]
    Serum bicarbonate

  27. Acid-base balance [ Time Frame: 10 days ]
    Arterialized venous blood potential of hydrogen (pH)

  28. Acid-base balance [ Time Frame: 10 days ]
    Urine pH

  29. Inflammation [ Time Frame: 10 days ]
    Serum C-reactive protein (CRP)

  30. Inflammation [ Time Frame: 10 days ]
    Serum albumin/CRP ratio

  31. Hematology [ Time Frame: 10 days ]

  32. Hematology [ Time Frame: 10 days ]

  33. Hematology [ Time Frame: 10 days ]
    Red blood cell (RBC) count

  34. Hematology [ Time Frame: 10 days ]
    White blood cell (WBC) count total

  35. Hematology [ Time Frame: 10 days ]
    WBC count differential (lymphocytes, basophils, monocytes, neutrophils, eosinophils)

  36. Hematology [ Time Frame: 10 days ]
    Platelet count

  37. Hematology [ Time Frame: 10 days ]
    Mean corpuscular hemoglobin (MCH)

  38. Hematology [ Time Frame: 10 days ]
    Mean corpuscular hemoglobin concentration (MCHC)

  39. Hematology [ Time Frame: 10 days ]
    Mean corpuscular volume (MCV)

  40. Coagulation [ Time Frame: 10 days ]
    Prothrombin time (Quick)

  41. Coagulation [ Time Frame: 10 days ]
    Activated partial thromboplastin time (APTT)

  42. Coagulation [ Time Frame: 10 days ]
    International normalized ratio (INR)

  43. Serum chemistry [ Time Frame: 10 days ]
    Glutamate oxaloacetate transaminase (GOT)/Aspartate aminotransferase (AST)

  44. Serum chemistry [ Time Frame: 10 days ]
    Glutamate-pyruvate transaminase (GPT)/Alanine transaminase (ALT)

  45. Serum chemistry [ Time Frame: 10 days ]
    Uric acid

  46. Serum chemistry [ Time Frame: 10 days ]
    Creatine kinase (CK)

  47. Serum chemistry [ Time Frame: 10 days ]
    Troponin T if CK is elevated

  48. Serum chemistry [ Time Frame: 10 days ]

  49. Adverse Events [ Time Frame: 52 days ]
    Adverse Events

  50. Vital signs [ Time Frame: 10 days ]
    Systolic and diastolic blood pressure

  51. Vital signs [ Time Frame: 10 days ]
    Pulse rate

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Written informed consent
  2. Non-dialysed male and female CKD patients with expected start of dialysis ≥ 3 months
  3. eGFR ≥5 to < 30 ml/min/1.73 m2
  4. Stable renal function at least 12 weeks before enrollment, defined by change in serum creatinine ≤ 80 µmol/L
  5. Body mass index (BMI): ≥ 22 kg/m² and ≤ 35 kg/m2
  6. Age: ≥ 40 to ≤ 75 years
  7. Eligible physical status of the patient for participation in the study upon assessment of the investigator based on medical history, physical examination and clinical laboratory parameters

Exclusion Criteria:

  1. Existing gastrointestinal diseases or pathological findings (e.g. heart, liver, or lung failure), which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient (e.g. persistent or frequent episodes of anorexia, vomiting, or diarrhea)
  2. Active cancer
  3. Diabetes treated with standard pharmacotherapy
  4. HbA1c ≥ 48 mmol/mol, and/or fasting blood glucose ≥ 126 mg/dl (≥ 7 mmol/L))
  5. Evidence of chronic infection or chronic inflammation; evidence of acute infection or acute inflammation
  6. C-reactive protein (CRP) > 20 mg/L determined at screening examination
  7. Known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparation
  8. Severe allergies or multiple drug allergies if judged as relevant for the clinical trial by the investigator
  9. Patients suffering from hypercalcaemia with a serum calcium ≥ 2.9 mmol/L performed on screening examination
  10. Major disorder of amino acid metabolism, e.g. hereditary diseases
  11. Hospitalization within the previous 1 month
  12. Proteinuria > 3 g/day
  13. Regular intensive exercise
  14. Ingestion of creatine supplements within the previous 1 month
  15. Intake of other anabolic or anti catabolic agents within the previous 1 month
  16. Any change of the chronic medication within 1 month before screening
  17. Autosomal dominant polycystic kidney disease (ADPKD)
  18. Positive anti-HIV-test (if positive to be verified by western blot), Hepatitis B surface antigen (HBsAG)-test (if positive to be verified by test for hepatitis B core antigen (HBc)- Immunoglobulin M (IgM)) or anti-hepatitis C virus (HCV)-test
  19. Current drug or alcohol dependence
  20. Blood donation (including donation of plasma and platelets) or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the patient
  21. Participation in an interventional clinical trial during the last 2 months prior to individual enrolment of the patient
  22. Patients who report a frequent occurrence of migraine attacks (i.e. at least once per month)
  23. History of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
  24. Change in habits of physical activity within the last 2 months for at least 7 days (e.g. immobilisation due to bed rest, immobilisation of a leg or other big muscle groups)
  25. Positive pregnancy test at screening examination
  26. Pregnant or lactating women
  27. Not willing to apply highly effective contraceptive methods [i.e. combined (estrogen and progestogen containing) hormonal contraception e.g. oral, intravaginal, transdermal and progestogen-only hormonal contraception e.g. oral, injectable, implantable as well as intrauterine device (IUD) and intrauterine hormone-releasing system (IUS) in combination with male condom; bilateral tubal occlusion, vasectomised partner or sexual abstinence]
  28. Patients suspected or known not to follow instructions
  29. Patients who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial

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): NCT03077048

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Thomayer Hospital Clinical - Pharmacology Unit (CPU)
Prague, Czechia, 140 59
Sponsors and Collaborators
Fresenius Kabi
EastHORN Clinical Services in CEE
MLM Medical Labs GmbH
ALS Czech Republic, s.r.o.
PCG Clinical Services AB
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Study Chair: John F Stover, M.D. Fresenius Kabi
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Responsible Party: Fresenius Kabi
ClinicalTrials.gov Identifier: NCT03077048    
Other Study ID Numbers: Keto-022-CP1
2016-003854-34 ( EudraCT Number )
First Posted: March 10, 2017    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Fresenius Kabi:
Chronic kidney disease
Additional relevant MeSH terms:
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Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases