NCT03077048

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Mar 2017

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 1, 2017

Completed
9 days until next milestone

First Posted

Study publicly available on registry

March 10, 2017

Completed
20 days until next milestone

Study Start

First participant enrolled

March 30, 2017

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 27, 2018

Completed
5 days until next milestone

Study Completion

Last participant's last visit for all outcomes

May 2, 2018

Completed
Last Updated

May 14, 2018

Status Verified

May 1, 2018

Enrollment Period

1.1 years

First QC Date

March 1, 2017

Last Update Submit

May 11, 2018

Conditions

Renal Insufficiency, Chronic

Keywords

CKDKetosterilketo-acidsketoanaloguesChronic kidney disease

Outcome Measures

Primary Outcomes (11)

  • Impact of Ketosteril® on the generation of nitrogenous waste products

    Serum urea

    10 days

  • Impact of Ketosteril® on the generation of nitrogenous waste products

    Urine urea

    10 days

  • Impact of Ketosteril® on the generation of nitrogenous waste products

    Nitrogen balance

    10 days

  • Impact of Ketosteril® on the generation of nitrogenous waste products

    Normalized protein catabolic rate (nPCR)

    10 days

  • Protein metabolism

    Serum total proteins

    10 days

  • Protein metabolism

    Albumin

    10 days

  • Protein metabolism

    Transthyretin

    10 days

  • Protein metabolism

    Transferrin

    10 days

  • Markers of anabolic signaling

    Serum Insulin-like growth factor (IGF)-I

    10 days

  • Markers of anabolic signaling

    Insulin like growth factor (IGF)-II

    10 days

  • Markers of anabolic signaling

    IGF-binding protein 3

    10 days

Secondary Outcomes (51)

  • Renal function

    10 days

  • Renal function

    10 days

  • Renal function

    10 days

  • Renal function

    10 days

  • Renal function

    10 days

  • +46 more secondary outcomes

Study Arms (2)

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

Drug: Ketosteril®

Interventions

Ketosteril®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.

Also known as: EV product code: PRD1170237
Supplemented low protein diet

Eligibility Criteria

Age40 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Thomayer Hospital Clinical - Pharmacology Unit (CPU)

Prague, 140 59, Czechia

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

ketosteril

Condition Hierarchy (Ancestors)

Renal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • John F Stover, M.D.

    Fresenius Kabi

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 1, 2017

First Posted

March 10, 2017

Study Start

March 30, 2017

Primary Completion

April 27, 2018

Study Completion

May 2, 2018

Last Updated

May 14, 2018

Record last verified: 2018-05

Data Sharing

IPD Sharing
Will not share

Locations

CZ(1)