Protein metabolism in chronic kidney disease

ISRCTN	ISRCTN64383094
DOI	https://doi.org/10.1186/ISRCTN64383094
Protocol serial number	N/A
Sponsor	Fresenius Kabi Deutschland GmbH (Germany)
Funder	Fresenius Kabi (Germany) - Ketosteril Award

Submission date: 18/01/2013
Registration date: 21/02/2013
Last edited: 22/06/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Protein-energy wasting (PEW) is common in patients with chronic kidney disease. It is a condition where the body has decreased stores of protein and energy and is associated with an increased risk of death. The aim of this study is to investigate the response to a low protein diet and a keto/amino acid supplemented very low protein diet in patients with chronic kidney disease.

Who can participate?
Patients aged 18 to 79 with chronic kidney disease

What does the study involve?
The study is composed of two different studies. In study A participants eat a usual-protein diet followed by a low-protein diet to find out how skeletal muscle protein turnover adapts. Study B consists of four six-week periods: the enrollment period, a low-protein diet period, a keto/amino acid supplemented very low protein diet period, and another low-protein diet period. Protein turnover (both whole body and muscle) is measured at the start of the study and at the end of each six-week period.

What are the possible benefits and risks of participating?
The study provides new information on how the body adapts to a low protein diet, and may be helpful for the understanding of their nutritional safety. The study involves the use of stable isotopes of naturally occurring amino acids, a procedure which is not harmful. The possible risks of measuring muscle protein turnover are those related to cannulation (where a tube is inserted into a blood vessel).

Where is the study run from?
Università degli studi di Genova (Italy)

When is the study starting and how long is it expected to run for?
January 2013 to June 2014

Who is funding the study?
Fresenius Kabi (Germany)

Who is the main contact?
Prof. Giacomo Garibotto
gari@unige.it

Contact information

Prof Giacomo Garibotto
Scientific

Viale Benedetto xv
Genoa
16132
Italy

Email	gari@unige.it

Study information

Primary study design	Interventional
Study design	Non-randomized prospective self-controlled crossover trial
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	Effects of a low protein diet and of a keto/amino acid supplemented very low protein diet on muscle protein metabolism and myostatin in patients with chronic kidney disease
Study acronym	PMCKD
Study objectives	The hypothesis is that the use of keto/amino acid supplements may partially or totally reverse the abnormal amino acid metabolism thus counteracting the uremia-related muscle cell loss and catabolic events.
Ethics approval(s)	IRCCS Azienda Ospedaliera Universitaria San Martino- IST Istituto Nazionale per la Ricerca sul Cancro, 13/04/2012, ref: 7/2012
Health condition(s) or problem(s) studied	Chronic kidney disease
Intervention	Low protein diet or supplemented very low protein dieT (vLPD) The research protocol is composed of two different studies: Study A: to determine how skeletal muscle protein metabolism adapt to a low protein diet, forearm protein turnover will be evaluated in the same CKD patients assigned to a usual-protein diet (1.1 g/kg/day, 30-35 kcalday), followed by a low-protein diet (LPD) (0.8 g/kg, followed by 0.55 g/kg, 30-35 kcal/Kg/day). Each time period of study is 6 weeks, with total length of period of time during which patient will be followed up of 18-24 weeks. To determine the muscle responses to a supplemented vLPD (0,45 g/kg, supplemented with 0.1 g/kg Ketosteril, 30-35 kcal/Kg/day) Study B: protein turnover (both whole body and muscle), muscle and plasma myostatin, muscle apoptosis, muscle proteolytic-related genes and intracellular insulin signaling, will be studied in a prospective cross-over trial with CKD patients serving as their own controls. Study B consists of four six-week consecutive periods: the enrollment period, the baseline (LPD) period, the treatment period (supplemented protein-restricted, vLPD) and the wash-out LPD period .
Intervention type	Other
Primary outcome measure(s)	Protein metabolism measured at baseline and at the end of each six-week experimental period
Key secondary outcome measure(s)	Serum/muscle myostatin measured at baseline and at the end of each six-week experimental period
Completion date	06/06/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	79 Years
Sex	All
Target sample size at registration	20
Key inclusion criteria	1. Aged 18-79, both males and females 2. Non-diabetic CKD (Stages 4-5, estimated glomerular filtration rate [eGFR] 12-25 ml/min) 3. Compliance to treatment
Key exclusion criteria	1. Evidence of congestive heart failure 2. Incapable of following study requirements to control diet 3. A recent myocardial infarction 4. Pregnancy 5. Unstable renal function 6. Recent (<3 months) infection history 7. Clinical evidence of gastrointestinal or liver diseases 8. Alcoholism 9. Drug abuse 10. Final diagnosis of malignancy
Date of first enrolment	10/01/2013
Date of final enrolment	06/06/2014

Locations

Countries of recruitment

Italy

Study participating centre

Viale Benedetto xv

Genoa
16132
Italy

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

22/06/2017: Plain English summary added.