Short-term Metabolic Effects of Ketosteril® Supplemented Low Protein Diet in Pre-dialysis Chronic Kidney Disease (CKD) Patients

NCT ID: NCT03077048

Last Updated: 2018-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-30
• Study Completion Date: 2018-05-02

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.

Conditions

Renal Insufficiency, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Low protein diet

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

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

Group Type: EXPERIMENTAL

Ketosteril®

Intervention Type: DRUG

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.

Interventions

Ketosteril®

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.

Intervention Type: DRUG

Other Intervention Names

EV product code: PRD1170237

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EastHORN Clinical Services in CEE

UNKNOWN

Sponsor Role: collaborator

MLM Medical Labs GmbH

INDUSTRY

Sponsor Role: collaborator

ALS Czech Republic, s.r.o.

UNKNOWN

Sponsor Role: collaborator

PCG Clinical Services AB

UNKNOWN

Sponsor Role: collaborator

Fresenius Kabi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John F Stover, M.D.

Role: STUDY_CHAIR

Fresenius Kabi

Locations

Thomayer Hospital Clinical - Pharmacology Unit (CPU)

Prague, , Czechia

Countries

Czechia

Other Identifiers

2016-003854-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Keto-022-CP1

Identifier Type: -

Identifier Source: org_study_id