Ketoanalogue Supplementation for Muscle Protection in CKD 4 and 5 Patients With Moderately Low Protein Diet (KETO-PROT-ACTION) (KETOPROTACTION)

Ketoanalogue Supplementation for Muscle Protection in CKD 4 and 5 Patients With Moderately Low Protein Diet

Chronic kidney disease (CKD) complicates many pathologies and the rapid increase in its prevalence constitutes a major public health concern. Whatever the cause of kidney failure, high protein consumption is a factor of progression to end-stage kidney disease. A low-protein (0.6 g/kg/d) or a very low-protein (0.3 g/kg/d) diet associated with supplementation with amino acids and/or keto acid analogues (KA) slows down renal function deterioration and prolongs the time before dialysis start. Difficulties in strict protein restriction implementation limit its use to a minority of CKD patients and are difficult to implement in real life.

Recently KDOQI guidelines have recommended a dietary protein intake of 0.55 to 0.6 g/kg/d in CKD 3 to 5 non-diabetic patients "metabolically stable" and 0.6 to 0.8 g/kg/d in diabetic patients. However, the International Society of Renal Nutrition and Metabolism and the French guidelines about management of CKD propose to maintain a protein intake between 0.6 and 0.8 g/kg/d for all patients and as near as possible to 0.6 g/kg/d. This is because for a population, a mean value of 0.66 g/kg/d insures that 95% of patients are above 0.55 g/kg/d (the minimum requirement to avoid a negative nitrogen balance).

Experimental studies and few clinical studies suggest a protective effect of KA supplementation on uremic sarcopenia. Interestingly this effect is also observed in patients with a protein intake of 0.6 to 0.8 g/kg/d and with a dose of KA reduced by half compared to the dose used with VLPD. Moreover, in a preliminary study, we found a nephroprotective effect of KA (1 tablet/5kg body weight) in patients with an average dietary protein intake of 0.7 g/kg/d suggesting a specific effect of KA beyond protein restriction.

The hypothesis is therefore that KA treatment (1 tablet/10kg), together with a dietary protein intake between 0.6 and 0.8g/kg/d, prevent muscle mass loss in patients with stages 4 and 5 CKD. If these results were confirmed, this could expand the population that could benefit from KA supplementation.

Study Overview

• Status: Recruiting
• Conditions: Kidney Disease, Chronic
• Intervention / Treatment: Drug: Keto Acid

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lise Laclautre; Phone Number: +334.73754.963; Email: promo_interne_drci@chu-clermontferrand.fr

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • Recruiting
    • CHU de Clermont-Ferrand
    • Principal Investigator: Julien ANIORT
    • Contact: Lise Laclautre; Email: promo_interne_drci@chu-clermontferrand.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women
• Older than 18 years of age
• Stage 4 or 5 CKD (eGFR with CKD-EPI 2009 creatinine equation < 30 mL/min/m2), whitout renal replacement therapy or kidney transplantation
• Protein intake 0.6-0.8 g/kg/d (estimated with Moroni formula)
• Social security cover
• Written informed consent

Exclusion Criteria:

• Hospitalization in the past 3 months
• Corticosteroids (> 7.5 mg/d), cytotoxic or immunosuppressive drugs
• Severe symptomatic heart (NYHA 3 or 4) or liver failure (Child Pugh B or C)
• Respiratory failure requiring oxygenotherapy
• Ongoing infection, autoimmune disease or cancer
• Pregnant (e.g., positive human chorionic gonadotrophin [HCG] test) or lactating patients

• Risk of pregnancy: any woman who does not fulfil one of the following criteria:

  • post-menopausal (aged > 45 years with amenorrhea for more than 2 years, or of any age with amenorrhea for more than 6 months and an FSH level > 40 mUI / mL)
  • permanent sterilisation (e.g., occlusion/bilateral ligature of the fallopian tubes, hysterectomy, bilateral salpingectomy, bilateral ovariectomy) or constitutional sterility
  • of childbearing age and using an efficient method of contraception, begun at least 28 days before inclusion. Efficient contraception methods are: oral, injectable or implantable hormonal methods intra-uterine devices sterilisation of the male partner if he is the sole partner abstinence, if compatible with the preferred and usual lifestyle of the individual NB: if child bearing potential changes during the study, the woman must start taking one of the efficient methods of contraception as described above.
• Patients with psychiatric or cognitive disorders rendering them unable to give written informed consent
• Patients unwilling to participate in the study
• Hypersensitivity to the active substances in Ketosteril®
• Hypercalcaemia
• Hypophosphatemia
• Patient under a legal protection (curatorship or tutorship)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Keto acid analog; Current practice + Keto acid analog (1 tablet / 10 kg body weight) Current practice: protein intake target of 0.6 g/kg/d in order to achieve a dietary protein intake of 0.6 to 0.8 g/kg/d (50% animal protein 50 % plant protein) and total energy intake of 25-35 kcal/kg/d.	Drug: Keto Acid; Keto acid analog Ketosteril (1 tablet / 10 kg body weight)
No Intervention: Control; Current practice: protein intake target of 0.6 g/kg/d in order to achieve a dietary protein intake of 0.6 to 0.8 g/kg/d (50% animal protein 50 % plant protein) and total energy intake of 25-35 kcal/kg/d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Appendicular muscle mass measured by DEXA	measured by DEXA	at 12 months

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Julien Aniort, CHU de Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: January 20, 2026
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic; Organic Chemicals; Carboxylic Acids; Keto Acids
• Other Study ID Numbers: RBHP 2023 ANIORT 2; 2024-516764-29-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No