Renal Insufficiency, Chronic
Conditions
Keywords
CKD, Ketosteril, keto-acids, ketoanalogues, Chronic kidney disease
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.
Interventions
DRUGKetosteril®
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.
Sponsors
EastHORN Clinical Services in CEE
MLM Medical Labs GmbH
ALS Czech Republic, s.r.o.
PCG Clinical Services AB
Fresenius Kabi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact of Ketosteril® on the generation of nitrogenous waste products | 10 days | Serum urea |
| Protein metabolism | 10 days | Serum total proteins |
| Markers of anabolic signaling | 10 days | Serum Insulin-like growth factor (IGF)-I |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lipid profile | 10 days | Triglycerides |
| Mineral status | 10 days | Sodium |
| Acid-base balance | 10 days | Serum bicarbonate |
| Inflammation | 10 days | Serum C-reactive protein (CRP) |
| Renal function | 10 days | Proteinuria |
| Coagulation | 10 days | Prothrombin time (Quick) |
| Serum chemistry | 10 days | Glutamate oxaloacetate transaminase (GOT)/Aspartate aminotransferase (AST) |
| Adverse Events | 52 days | Adverse Events |
| Vital signs | 10 days | Systolic and diastolic blood pressure |
| Hematology | 10 days | Hematocrit |
| Nutritional status | 10 days | Body weight |
| Glucose metabolism | 10 days | Fasting blood glucose |
Countries
Czechia
Outcome results
None listed