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

University Hospital, Clermont-Ferrand

Status and phase: Enrolling; Phase 3

Conditions: Kidney Disease, Chronic

Treatments: Drug: Keto Acid

Study type: Interventional

Funder types: Other

Identifiers

NCT07374042

RBHP 2023 ANIORT 2

2024-516764-29-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Keto acid analog

Experimental group

Description:

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.

Treatment:

Drug: Keto Acid

Control

No Intervention group

Description:

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.