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

Renal Insufficiency, Chronic Clinical Trial

— CKD  

Official title:

Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis CKD Patients - A Randomized, Controlled, Open-labelled Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03077048
• Other study ID #: Keto-022-CP1
• Secondary ID: 2016-003854-34
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 30, 2017
• Est. completion date: May 2, 2018

Study information

• Verified date: May 2018
• Source: Fresenius Kabi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: May 2, 2018
• Est. primary completion date: April 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Diseases
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

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.

Locations

Country	Name	City	State
Czechia	Thomayer Hospital Clinical - Pharmacology Unit (CPU)	Prague

Sponsors (5)

Lead Sponsor	Collaborator
Fresenius Kabi	ALS Czech Republic, s.r.o., EastHORN Clinical Services in CEE, MLM Medical Labs GmbH, PCG Clinical Services AB

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact of Ketosteril® on the generation of nitrogenous waste products	Serum urea	10 days
Primary	Impact of Ketosteril® on the generation of nitrogenous waste products	Urine urea	10 days
Primary	Impact of Ketosteril® on the generation of nitrogenous waste products	Nitrogen balance	10 days
Primary	Impact of Ketosteril® on the generation of nitrogenous waste products	Normalized protein catabolic rate (nPCR)	10 days
Primary	Protein metabolism	Serum total proteins	10 days
Primary	Protein metabolism	Albumin	10 days
Primary	Protein metabolism	Transthyretin	10 days
Primary	Protein metabolism	Transferrin	10 days
Primary	Markers of anabolic signaling	Serum Insulin-like growth factor (IGF)-I	10 days
Primary	Markers of anabolic signaling	Insulin like growth factor (IGF)-II	10 days
Primary	Markers of anabolic signaling	IGF-binding protein 3	10 days
Secondary	Renal function	Proteinuria	10 days
Secondary	Renal function	Albuminuria	10 days
Secondary	Renal function	Serum and urine creatinine	10 days
Secondary	Renal function	Serum and urine urea	10 days
Secondary	Renal function	Serum urea nitrogen (SUN)	10 days
Secondary	Renal function	Urine nitrogen	10 days
Secondary	Renal function	Glomerular filtration rate estimated from serum creatinine (eGFR)	10 days
Secondary	Renal function	Albumin-creatinine ratio	10 days
Secondary	Renal function	Urea clearance	10 days
Secondary	Nutritional status	Body weight	10 days
Secondary	Nutritional status	Body Mass Index (BMI)	10 days
Secondary	Nutritional status	Body composition (via Bio Impedance Spectroscopy)	10 days
Secondary	Nutritional status	SUN-to-creatinine ratio	10 days
Secondary	Glucose metabolism	Fasting blood glucose	10 days
Secondary	Lipid profile	Triglycerides	10 days
Secondary	Lipid profile	Cholesterol	10 days
Secondary	Lipid profile	High-density lipoprotein (HDL)/Low-density lipoprotein (LDL)-cholesterol	10 days
Secondary	Mineral status	Sodium	10 days
Secondary	Mineral status	Calcium	10 days
Secondary	Mineral status	Potassium	10 days
Secondary	Mineral status	Magnesium	10 days
Secondary	Mineral status	Phosphate (serum and urine)	10 days
Secondary	Mineral status	Alkaline phosphatase	10 days
Secondary	Mineral status	Fibroblast growth factor (FGF)-23	10 days
Secondary	Mineral status	25-hydroxycholecalciferol (serum)	10 days
Secondary	Acid-base balance	Serum bicarbonate	10 days
Secondary	Acid-base balance	Arterialized venous blood potential of hydrogen (pH)	10 days
Secondary	Acid-base balance	Urine pH	10 days
Secondary	Inflammation	Serum C-reactive protein (CRP)	10 days
Secondary	Inflammation	Serum albumin/CRP ratio	10 days
Secondary	Hematology	Hematocrit	10 days
Secondary	Hematology	Hemoglobin	10 days
Secondary	Hematology	Red blood cell (RBC) count	10 days
Secondary	Hematology	White blood cell (WBC) count total	10 days
Secondary	Hematology	WBC count differential (lymphocytes, basophils, monocytes, neutrophils, eosinophils)	10 days
Secondary	Hematology	Platelet count	10 days
Secondary	Hematology	Mean corpuscular hemoglobin (MCH)	10 days
Secondary	Hematology	Mean corpuscular hemoglobin concentration (MCHC)	10 days
Secondary	Hematology	Mean corpuscular volume (MCV)	10 days
Secondary	Coagulation	Prothrombin time (Quick)	10 days
Secondary	Coagulation	Activated partial thromboplastin time (APTT)	10 days
Secondary	Coagulation	International normalized ratio (INR)	10 days
Secondary	Serum chemistry	Glutamate oxaloacetate transaminase (GOT)/Aspartate aminotransferase (AST)	10 days
Secondary	Serum chemistry	Glutamate-pyruvate transaminase (GPT)/Alanine transaminase (ALT)	10 days
Secondary	Serum chemistry	Uric acid	10 days
Secondary	Serum chemistry	Creatine kinase (CK)	10 days
Secondary	Serum chemistry	Troponin T if CK is elevated	10 days
Secondary	Serum chemistry	Chloride	10 days
Secondary	Adverse Events	Adverse Events	52 days
Secondary	Vital signs	Systolic and diastolic blood pressure	10 days
Secondary	Vital signs	Pulse rate	10 days