Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis CKD Patients - A Randomized, Controlled, Open-labelled Clinical Trial
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Fresenius Kabi
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- Impact of Ketosteril® on the generation of nitrogenous waste products
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 40 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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
Intervention: Ketosteril® (Drug)
Outcomes
Primary Outcomes
Impact of Ketosteril® on the generation of nitrogenous waste products
Time Frame: 10 days
Normalized protein catabolic rate (nPCR)
Protein metabolism
Time Frame: 10 days
Transferrin
Markers of anabolic signaling
Time Frame: 10 days
IGF-binding protein 3
Secondary Outcomes
- Renal function(10 days)
- Nutritional status(10 days)
- Glucose metabolism(10 days)
- Lipid profile(10 days)
- Mineral status(10 days)
- Acid-base balance(10 days)
- Inflammation(10 days)
- Hematology(10 days)
- Coagulation(10 days)
- Serum chemistry(10 days)
- Adverse Events(52 days)
- Vital signs(10 days)