Evaluation of Ketoanalogue Supplementation on Sarcopenia in Stage 4 and 5 Chronic Kidney Disease Patients on a Moderately Low Protein Diet

The primary objective of this study is to evaluate the effect of **ketoanalogue** supplementation on sarcopenia over a 12-month period in patients with stage 4 or 5 chronic kidney disease (CKD) who maintain a dietary protein intake between 0.6 and 0.8 g/kg/day. Sarcopenia, characterized by the loss of muscle mass and function, is a significant concern in CKD patients due to its impact on physical performance and quality of life. Addressing sarcopenia in this population is clinically relevant as it may improve patient outcomes and reduce morbidity.

Secondary objectives include:

• Determining the effects of ketoanalogue supplementation on the decline of renal function in the same patient cohort.
• Assessing the impact of ketoanalogue supplementation on mineral and bone disorders, which are common complications in advanced CKD.
• Evaluating the effects on metabolism, which may provide insights into the broader physiological benefits of ketoanalogue supplementation in CKD patients.

The clinical trial involves participants diagnosed with **chronic kidney disease** (CKD), specifically those in stage 4 or 5, characterized by an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m², as calculated using the CKD-EPI 2009 creatinine equation. The study population includes both male and female subjects, all of whom are over the age of 18. Participants are required to have a dietary protein intake ranging from 0.6 to 0.8 g/kg/day, as estimated through a dietary survey. The trial does not include a vulnerable population. All participants must have social security coverage and provide written informed consent. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the effect of **ketoanalogue** supplementation on sarcopenia in patients with stage 4 or 5 chronic kidney disease (CKD) who are on a moderately low protein diet. This study is structured as a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know who is receiving the treatment or placebo, thus minimizing bias. The trial is expected to last for a total duration of 12 months, with participant involvement spanning the same period.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (over 18 years), CKD stage, protein intake, and informed consent. Following the initial screening, participants will attend follow-up visits at 3, 6, 9, and 12 months. These visits are designed to monitor various health parameters, including weight, BMI, albumin levels, and muscle mass index, among others. The primary endpoint is the muscle mass index measured by DEXA at 12 months, while secondary endpoints include assessments of weight, BMI, serum lipids, glycemia, and other biochemical markers at specified intervals.

The end-of-study visit will occur at the 12-month mark, where final assessments will be conducted to evaluate the long-term effects of the supplementation. Participants are expected to remain in the study for the full duration unless conditions arise that necessitate early termination, such as adverse reactions or withdrawal of consent. The trial aims to provide comprehensive data on the efficacy of ketoanalogue supplementation in preserving muscle mass in CKD patients, contributing valuable insights into potential therapeutic strategies for this population.

The clinical trial involves the administration of **Ketosteril Ketoacid film-coated tablets** as the experimental medication. These tablets are designed to provide ketoanalogue supplementation for muscle protection in patients with stage 4 or 5 chronic kidney disease (CKD) who are on a moderately low protein diet. The pharmaceutical form of the medication is a film-coated tablet, and it is administered orally. The active substances in the tablets include a combination of amino acids and keto acids: L-lysine acetate, L-tryptophan, L-histidine, lysine acetate, L-threonine, L-tyrosine, keto-isoleucine calcium, keto-leucine calcium, keto-valine calcium, hydroxi-methionine calcium, and alpha-ketophenylalanine calcium. The maximum daily dose is 67 mg/kg, with a total maximum dose of 24,455 mg/kg over the treatment period. The treatment duration is set for a maximum of 12 months.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the effects of the experimental medication, Ketosteril, in the context of the trial's main objective, which is to assess its impact on sarcopenia over a 12-month period. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

The efficacy of the clinical trial titled "Ketoanalogue Supplementation for Muscle Protection in CKD 4 and 5 Patients with Moderately Low Protein Diet" will be assessed using a combination of primary and secondary endpoints. The primary endpoint is the **muscle mass index** measured by DEXA (appendicular lean mass kg/m²) at 12 months. This measurement will provide an indication of the effect of ketoanalogue supplementation on sarcopenia in patients with stage 4 or 5 Chronic Kidney Disease (CKD).

Secondary endpoints include a variety of parameters measured at different timepoints throughout the trial. These include weight and BMI at 3, 6, and 12 months; concentrations of albumin, prealbumin, and CRP at 3, 6, 9, and 12 months; serum lipids and glycemia at 12 months; skin fold and mid-arm muscle circumference; grip strength measured by dynamometry at 12 months; muscle performance evaluated by a walking speed test over 4 meters at 12 months; serum calcium and phosphate at 3, 6, 9, and 12 months; parathormone at 3, 6, 9, and 12 months; 25OH Vitamin D2 + D3 at 3, 6, 9, and 12 months; bone mineral density measured by DEXA at 12 months; use and dosage of phosphate binders; time to renal replacement therapy start; estimated GFR using the 2012 CKD EPI creatinine and cystatin C equation at 12 months; and proteinuria at 12 months.

These efficacy parameters will be collected and analyzed using validated methods and tools, such as DEXA for muscle mass and bone mineral density, and dynamometry for grip strength. The schedule for these assessments is structured to provide comprehensive data on the impact of the intervention over the 12-month period.