Clinical trial NCT03077048: Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis Chronic Kidney Disease (CKD) Patients
Official title: Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis CKD Patients - A Randomized, Controlled, Open-labelled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Renal Insufficiency, Chronic
Keywords: CKD
Ketosteril
keto-acids
ketoanalogues
Chronic kidney disease
Lead sponsor: Fresenius Kabi
Sponsor class: INDUSTRY
Collaborators: name: EastHORN Clinical Services in CEE
name: MLM Medical Labs GmbH
name: ALS Czech Republic, s.r.o.
name: PCG Clinical Services AB
First posted: 2017-03-10
Enrollment: 23
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Impact of Ketosteril® on the generation of nitrogenous waste products
timeFrame: 10 days
measure: Impact of Ketosteril® on the generation of nitrogenous waste products
timeFrame: 10 days
measure: Impact of Ketosteril® on the generation of nitrogenous waste products
timeFrame: 10 days
measure: Impact of Ketosteril® on the generation of nitrogenous waste products
timeFrame: 10 days
measure: Protein metabolism
timeFrame: 10 days
measure: Protein metabolism
timeFrame: 10 days
measure: Protein metabolism
timeFrame: 10 days
measure: Protein metabolism
timeFrame: 10 days
measure: Markers of anabolic signaling
timeFrame: 10 days
measure: Markers of anabolic signaling
timeFrame: 10 days
measure: Markers of anabolic signaling
timeFrame: 10 days
Secondary outcomes:
measure: Renal function
timeFrame: 10 days
measure: Renal function
timeFrame: 10 days
measure: Renal function
timeFrame: 10 days
measure: Renal function
timeFrame: 10 days
measure: Renal function
timeFrame: 10 days
measure: Renal function
timeFrame: 10 days
measure: Renal function
timeFrame: 10 days
measure: Renal function
timeFrame: 10 days
measure: Renal function
timeFrame: 10 days
measure: Nutritional status
timeFrame: 10 days
measure: Nutritional status
timeFrame: 10 days
measure: Nutritional status
timeFrame: 10 days
measure: Nutritional status
timeFrame: 10 days
measure: Glucose metabolism
timeFrame: 10 days
measure: Lipid profile
timeFrame: 10 days
measure: Lipid profile
timeFrame: 10 days
measure: Lipid profile
timeFrame: 10 days
measure: Mineral status
timeFrame: 10 days
measure: Mineral status
timeFrame: 10 days
measure: Mineral status
timeFrame: 10 days
measure: Mineral status
timeFrame: 10 days
measure: Mineral status
timeFrame: 10 days
measure: Mineral status
timeFrame: 10 days
measure: Mineral status
timeFrame: 10 days
measure: Mineral status
timeFrame: 10 days
measure: Acid-base balance
timeFrame: 10 days
measure: Acid-base balance
timeFrame: 10 days
measure: Acid-base balance
timeFrame: 10 days
measure: Inflammation
timeFrame: 10 days
measure: Inflammation
timeFrame: 10 days
measure: Hematology
timeFrame: 10 days
measure: Hematology
timeFrame: 10 days
measure: Hematology
timeFrame: 10 days
measure: Hematology
timeFrame: 10 days
measure: Hematology
timeFrame: 10 days
measure: Hematology
timeFrame: 10 days
measure: Hematology
timeFrame: 10 days
measure: Hematology
timeFrame: 10 days
measure: Hematology
timeFrame: 10 days
measure: Coagulation
timeFrame: 10 days
measure: Coagulation
timeFrame: 10 days
measure: Coagulation
timeFrame: 10 days
measure: Serum chemistry
timeFrame: 10 days
measure: Serum chemistry
timeFrame: 10 days
measure: Serum chemistry
timeFrame: 10 days
measure: Serum chemistry
timeFrame: 10 days
measure: Serum chemistry
timeFrame: 10 days
measure: Serum chemistry
timeFrame: 10 days
measure: Adverse Events
timeFrame: 52 days
measure: Vital signs
timeFrame: 10 days
measure: Vital signs
timeFrame: 10 days
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Thomayer Hospital Clinical - Pharmacology Unit (CPU)
Study officials:
affiliation: Fresenius Kabi
name: John F Stover, M.D.
role: STUDY_CHAIR
References: