Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis Chronic Kidney Disease (CKD) Patients
- Conditions
- Renal Insufficiency, Chronic
- Interventions
- Drug: Ketosteril®
- Registration Number
- NCT03077048
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 23
- Written informed consent
- Non-dialysed male and female CKD patients with expected start of dialysis ≥ 3 months
- eGFR ≥5 to < 30 ml/min/1.73 m2
- Stable renal function at least 12 weeks before enrollment, defined by change in serum creatinine ≤ 80 µmol/L
- Body mass index (BMI): ≥ 22 kg/m² and ≤ 35 kg/m2
- Age: ≥ 40 to ≤ 75 years
- 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
- 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)
- Active cancer
- Diabetes treated with standard pharmacotherapy
- HbA1c ≥ 48 mmol/mol, and/or fasting blood glucose ≥ 126 mg/dl (≥ 7 mmol/L))
- Evidence of chronic infection or chronic inflammation; evidence of acute infection or acute inflammation
- C-reactive protein (CRP) > 20 mg/L determined at screening examination
- Known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparation
- Severe allergies or multiple drug allergies if judged as relevant for the clinical trial by the investigator
- Patients suffering from hypercalcaemia with a serum calcium ≥ 2.9 mmol/L performed on screening examination
- Major disorder of amino acid metabolism, e.g. hereditary diseases
- Hospitalization within the previous 1 month
- Proteinuria > 3 g/day
- Regular intensive exercise
- Ingestion of creatine supplements within the previous 1 month
- Intake of other anabolic or anti catabolic agents within the previous 1 month
- Any change of the chronic medication within 1 month before screening
- Autosomal dominant polycystic kidney disease (ADPKD)
- 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
- Current drug or alcohol dependence
- 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
- Participation in an interventional clinical trial during the last 2 months prior to individual enrolment of the patient
- Patients who report a frequent occurrence of migraine attacks (i.e. at least once per month)
- History of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
- 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)
- Positive pregnancy test at screening examination
- Pregnant or lactating women
- 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]
- Patients suspected or known not to follow instructions
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Supplemented low protein diet Ketosteril® 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
- Primary Outcome Measures
Name Time Method Protein metabolism 10 days Transferrin
Impact of Ketosteril® on the generation of nitrogenous waste products 10 days Normalized protein catabolic rate (nPCR)
Markers of anabolic signaling 10 days IGF-binding protein 3
- Secondary Outcome Measures
Name Time Method Coagulation 10 days International normalized ratio (INR)
Renal function 10 days Urea clearance
Nutritional status 10 days SUN-to-creatinine ratio
Glucose metabolism 10 days Fasting blood glucose
Lipid profile 10 days High-density lipoprotein (HDL)/Low-density lipoprotein (LDL)-cholesterol
Mineral status 10 days 25-hydroxycholecalciferol (serum)
Acid-base balance 10 days Urine pH
Inflammation 10 days Serum albumin/CRP ratio
Hematology 10 days Mean corpuscular volume (MCV)
Serum chemistry 10 days Chloride
Adverse Events 52 days Adverse Events
Vital signs 10 days Pulse rate
Trial Locations
- Locations (1)
Thomayer Hospital Clinical - Pharmacology Unit (CPU)
🇨🇿Prague, Czechia