Renal Insufficiency, ChronicPhase 1/2CKDNCT03077048
Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis Chronic Kidney Disease (CKD) Patients
A Phase 1/2 study testing Ketosteril® in people with Renal Insufficiency, Chronic, run by Fresenius Kabi at 1 site in Czechia.
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… Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Renal Insufficiency, Chronic
- What is being tested?
- Ketosteril®
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteCzechia
- Study dates
- 30 Mar 2017to 2 May 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 29Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Czechia1 site
Thomayer Hospital Clinical - Pharmacology Unit (CPU)
Prague, 140 59
About this study
Official title: Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis CKD Patients - A Randomized, Controlled, Open-labelled Clinical Trial
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.
Read more
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.
- Conditions
- Renal Insufficiency, Chronic
- Being tested
- Ketosteril®
- Keywords
- CKD, Ketosteril, keto-acids, ketoanalogues, Chronic kidney disease
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketosteril®Drug
Also called EV product code: PRD1170237
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.
| Study group | Role | What they receive |
|---|---|---|
| Low protein diet | No intervention | Low protein diet with 0.6 g protein/kg BW/day (20-30% high biological value) and an energy intake of 30-35 kcal/kg BW/day |
| Supplemented low protein diet | Experimental | 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 Receives: Drug: Ketosteril® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of Ketosteril® on the generation of nitrogenous waste products
Serum urea
Measured: 10 days
Impact of Ketosteril® on the generation of nitrogenous waste products
Urine urea
Measured: 10 days
Impact of Ketosteril® on the generation of nitrogenous waste products
Nitrogen balance
Measured: 10 days
Impact of Ketosteril® on the generation of nitrogenous waste products
Normalized protein catabolic rate (nPCR)
Measured: 10 days
Protein metabolism
Serum total proteins
Measured: 10 days
Protein metabolism
Albumin
Measured: 10 days
Protein metabolism
Transthyretin
Measured: 10 days
Protein metabolism
Transferrin
Measured: 10 days
Markers of anabolic signaling
Serum Insulin-like growth factor (IGF)-I
Measured: 10 days
Markers of anabolic signaling
Insulin like growth factor (IGF)-II
Measured: 10 days
Markers of anabolic signaling
IGF-binding protein 3
Measured: 10 days
Secondary outcomes (51)
Renal function
Proteinuria
Measured: 10 days
Renal function
Albuminuria
Measured: 10 days
Renal function
Serum and urine creatinine
Measured: 10 days
Renal function
Serum and urine urea
Measured: 10 days
Renal function
Serum urea nitrogen (SUN)
Measured: 10 days
Renal function
Urine nitrogen
Measured: 10 days
Renal function
Glomerular filtration rate estimated from serum creatinine (eGFR)
Measured: 10 days
Renal function
Albumin-creatinine ratio
Measured: 10 days
Renal function
Urea clearance
Measured: 10 days
Nutritional status
Body weight
Measured: 10 days
Nutritional status
Body Mass Index (BMI)
Measured: 10 days
Nutritional status
Body composition (via Bio Impedance Spectroscopy)
Measured: 10 days
Nutritional status
SUN-to-creatinine ratio
Measured: 10 days
Glucose metabolism
Fasting blood glucose
Measured: 10 days
Lipid profile
Triglycerides
Measured: 10 days
Lipid profile
Cholesterol
Measured: 10 days
Lipid profile
High-density lipoprotein (HDL)/Low-density lipoprotein (LDL)-cholesterol
Measured: 10 days
Mineral status
Sodium
Measured: 10 days
Mineral status
Calcium
Measured: 10 days
Mineral status
Potassium
Measured: 10 days
Mineral status
Magnesium
Measured: 10 days
Mineral status
Phosphate (serum and urine)
Measured: 10 days
Mineral status
Alkaline phosphatase
Measured: 10 days
Mineral status
Fibroblast growth factor (FGF)-23
Measured: 10 days
Mineral status
25-hydroxycholecalciferol (serum)
Measured: 10 days
Acid-base balance
Serum bicarbonate
Measured: 10 days
Acid-base balance
Arterialized venous blood potential of hydrogen (pH)
Measured: 10 days
Acid-base balance
Urine pH
Measured: 10 days
Inflammation
Serum C-reactive protein (CRP)
Measured: 10 days
Inflammation
Serum albumin/CRP ratio
Measured: 10 days
Hematology
Hematocrit
Measured: 10 days
Hematology
Hemoglobin
Measured: 10 days
Hematology
Red blood cell (RBC) count
Measured: 10 days
Hematology
White blood cell (WBC) count total
Measured: 10 days
Hematology
WBC count differential (lymphocytes, basophils, monocytes, neutrophils, eosinophils)
Measured: 10 days
Hematology
Platelet count
Measured: 10 days
Hematology
Mean corpuscular hemoglobin (MCH)
Measured: 10 days
Hematology
Mean corpuscular hemoglobin concentration (MCHC)
Measured: 10 days
Hematology
Mean corpuscular volume (MCV)
Measured: 10 days
Coagulation
Prothrombin time (Quick)
Measured: 10 days
Coagulation
Activated partial thromboplastin time (APTT)
Measured: 10 days
Coagulation
International normalized ratio (INR)
Measured: 10 days
Serum chemistry
Glutamate oxaloacetate transaminase (GOT)/Aspartate aminotransferase (AST)
Measured: 10 days
Serum chemistry
Glutamate-pyruvate transaminase (GPT)/Alanine transaminase (ALT)
Measured: 10 days
Serum chemistry
Uric acid
Measured: 10 days
Serum chemistry
Creatine kinase (CK)
Measured: 10 days
Serum chemistry
Troponin T if CK is elevated
Measured: 10 days
Serum chemistry
Chloride
Measured: 10 days
Adverse Events
Adverse Events
Measured: 52 days
Vital signs
Systolic and diastolic blood pressure
Measured: 10 days
Vital signs
Pulse rate
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2017
- Study start30 Mar 2017
- Primary completion27 Apr 2018
- Study completion2 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Insufficiency, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fresenius Kabi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- EastHORN Clinical Services in CEE, MLM Medical Labs GmbH, ALS Czech Republic, s.r.o., PCG Clinical Services AB
- Responsible party
- Sponsor
- Investigators
- John F Stover, M.D., Study chair, Fresenius Kabi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03077048
- Sponsor's protocol ID
- Keto-022-CP1
- Other IDs
- 2016-003854-34, 2016
- Acronym
- CKD
- Status last verified
- May 2018
- First submitted
- 1 Mar 2017
- Last updated
- 14 May 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis CKD Patients - A Randomized, Controlled, Open-labelled Clinical Trial
- ClinicalTrials.gov ID
- NCT03077048
- Acronym / sponsor ID
- CKD / Keto-022-CP1
- Conditions
- Renal Insufficiency, Chronic
- Keywords
- CKD, Ketosteril, keto-acids, ketoanalogues, Chronic kidney disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Fresenius KabiIndustry (pharma, biotech, devices)
- Collaborators
- EastHORN Clinical Services in CEE, MLM Medical Labs GmbH, ALS Czech Republic, s.r.o., PCG Clinical Services AB
- Study start
- 30 Mar 2017 (actual)
- Primary completion
- 27 Apr 2018 (actual)
- Study completion
- 2 May 2018 (actual)
- First posted
- 10 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low protein diet | No intervention | –Low protein diet with 0.6 g protein/kg BW/day (20-30% high biological value) and an energy intake of 30-35 kcal/kg BW/day |
| Supplemented low protein diet | Experimental | Drug: 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 |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketosteril®Also: EV product code: PRD1170237Patients 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. | Drug | Supplemented low protein diet |
Primary outcome
Impact of Ketosteril® on the generation of nitrogenous waste products
Time frame: 10 days
Serum urea
Impact of Ketosteril® on the generation of nitrogenous waste products
Time frame: 10 days
Urine urea
Impact of Ketosteril® on the generation of nitrogenous waste products
Time frame: 10 days
Nitrogen balance
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
Serum total proteins
Protein metabolism
Time frame: 10 days
Albumin
Protein metabolism
Time frame: 10 days
Transthyretin
Protein metabolism
Time frame: 10 days
Transferrin
Markers of anabolic signaling
Time frame: 10 days
Serum Insulin-like growth factor (IGF)-I
Markers of anabolic signaling
Time frame: 10 days
Insulin like growth factor (IGF)-II
Markers of anabolic signaling
Time frame: 10 days
IGF-binding protein 3
51 secondary outcomes
Renal function
Time frame: 10 days
Renal function
Time frame: 10 days
Renal function
Time frame: 10 days
Renal function
Time frame: 10 days
Renal function
Time frame: 10 days
Renal function
Time frame: 10 days
Renal function
Time frame: 10 days
Renal function
Time frame: 10 days
Renal function
Time frame: 10 days
Nutritional status
Time frame: 10 days
Nutritional status
Time frame: 10 days
Nutritional status
Time frame: 10 days
Nutritional status
Time frame: 10 days
Glucose metabolism
Time frame: 10 days
Lipid profile
Time frame: 10 days
Lipid profile
Time frame: 10 days
Lipid profile
Time frame: 10 days
Mineral status
Time frame: 10 days
Mineral status
Time frame: 10 days
Mineral status
Time frame: 10 days
Mineral status
Time frame: 10 days
Mineral status
Time frame: 10 days
Mineral status
Time frame: 10 days
Mineral status
Time frame: 10 days
Mineral status
Time frame: 10 days
Acid-base balance
Time frame: 10 days
Acid-base balance
Time frame: 10 days
Acid-base balance
Time frame: 10 days
Inflammation
Time frame: 10 days
Inflammation
Time frame: 10 days
Hematology
Time frame: 10 days
Hematology
Time frame: 10 days
Hematology
Time frame: 10 days
Hematology
Time frame: 10 days
Hematology
Time frame: 10 days
Hematology
Time frame: 10 days
Hematology
Time frame: 10 days
Hematology
Time frame: 10 days
Hematology
Time frame: 10 days
Coagulation
Time frame: 10 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John F Stover, M.D. study chair
Fresenius Kabi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ketosteril® in people with Renal Insufficiency, Chronic, run by Fresenius Kabi at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of Ketosteril® on the generation of nitrogenous waste products (time frame: 10 days). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2018.