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Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome

Phase 3
Recruiting
Conditions
Nephrotic Syndrome
Interventions
Drug: Ketosteril
Other: Medium Protein Diet (MPD)
Registration Number
NCT05716880
Lead Sponsor
Military Institute od Medicine National Research Institute
Brief Summary

The goal of this non-commercial clinical trial is to assess efficacy and safety of ketoanalogues of essential amino acids in the prevention of protein-energy wasting in nephrotic syndrome.

Detailed Description

Adult patients with new diagnosis or relapse of nephrotic syndrome and glomerular filtration rate of ≥ 30 mL/min/1.73m2 will be included in the study. Exclusion criteria will be a secondary cause of nephrotic syndrome, morbid obesity and severe diseases affecting nutritional status.

Participants will be randomly assigned to the intervention group (KA+MPD) or control group (MPD); randomization will be stratified by type of glomerular disease (podocytopathy or other type) and investigational site. The control group will follow the diet recommended in nephrotic syndrome - a medium protein diet (MPD) - under the care of a dietitian. Intervention group will receive Ketosteril (1 tablet for every 5 kg of ideal body weight) as an addition to the diet. All patients will also receive treatment for underlying glomerular disease in accordance with current guidelines and local practice.

The main objective is to assess the efficacy of Ketosteril as an add-on therapy in preventing the loss of lean tissue mass (LTM) over 6 months compared to a standard diet.

The additional aims include the assessment of muscle function parameters, nephrotic syndrome severity and laboratory indicators of catabolism.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
150
Inclusion Criteria
  • Nephrotic syndrome with serum albumin < 3.0 g/dL and daily proteinuria of > 3.5 g/day or > 50 mg/kg;
  • New diagnosis or relapse of nephrotic syndrome (defined as: proteinuria of < 2.0 g/day or uPCR < 2000 mg/g in the last 6 months prior to relapse and prednison dose equal to or less than 10 mg/day in the last 3 months prior relapse);
  • Glomerular filtration rate qual to or higher than 30 mL/min/1.73m2 based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Exclusion Criteria
  • Diabetic kidney disease;
  • Small vessels vasculitis;
  • Systemic lupus erythematosus;
  • Positive antinuclear antibodies, anti-dsDNA or antineutrophil cytoplasmic antibodies (ANCA);
  • Positive anti-HIV or anti-hepatitis C antibodies, HBsAg;
  • HbA1c >7%;
  • Monoclonal gammopathy;
  • Pregnancy;
  • Body mass index >= 40 kg/m2;
  • Severe acute or chronic disease affecting nutritional status;
  • Neoplasm;
  • Contraindication to Ketosteril;
  • Alcohol or drug abuse;
  • Mental disorders;
  • Failure to comply with medical recommendations, lack of cooperation;
  • Participation in other clinical trial or the use of Ketosteril in the last 1 year prior to screening.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
KA+MPDKetosterilKetosteril + Medium Protein Diet (MPD) for 12 months
KA+MPDMedium Protein Diet (MPD)Ketosteril + Medium Protein Diet (MPD) for 12 months
MPDMedium Protein Diet (MPD)Medium Protein Diet (MPD) for 12 months
Primary Outcome Measures
NameTimeMethod
Maximum loss of lean tissue mass6 months

The difference between the initial lean tissue mass (LTM) and the lowest LTM measured within 6 months, expressed in percentage. The non-inferiority hypothesis of Ketosteril use will be tested as the primary endpoint.

LTM will be measured with bioimpedance spectroscopy.

Secondary Outcome Measures
NameTimeMethod
Serum albumin6 months

Change in serum albumin level from baseline value; expressed in g/dL.

Uric acid6 months

Change in serum uric acid level from baseline; expressed in mg/dL.

6-minute walk test distance6 months

Change in distance walked in the 6-minute walk test from baseline value; expressed in meters.

Triglycerides6 months

Change in serum triglycerides level from baseline; expressed in mg/dL.

Unfavorable disease course12 months

The percentage of patients who experienced the unfavorable disease course including: glomerular disease related death; venous or arterial thromboembolic event; infection requiring hospital admission; acute kidney injury in the stage 2 or 3; sustained glomerular filtration rate reduction over 50% or initiation of kidney replacement therapy; unplanned hospital admission due to complications of nephrotic syndrome treatment.

Handgrip strength (HGS)6 months

Change in HGS value from baseline; expressed in kg.

Urinary protein/creatinine ratio (uPCR)6 months

Change in uPCR value from baseline; expressed in mg/g.

Glomerular filtration rate12 months

Change in glomerular filtration rate from baseline; expressed in mL/min/1.73m2.

Maximum loss of lean tissue mass6 months

The difference between the initial lean tissue mass (LTM) and the lowest LTM measured within 6 months, expressed in percentage. The superiority hypothesis of Ketosteril use will be tested as the secondary endpoint.

Neph-PEW diagnosis6 months

The percentage of patients meeting criteria of nephrotic syndrome-associated protein-energy wasting (neph-PEW): reduction of LTM by 3% within 3 months or by 5% within 6 months.

Low density lipoprotein (LDL)6 months

Change in serum LDL level from baseline; expressed in mg/dL.

Trial Locations

Locations (1)

Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine - National Research Institute

🇵🇱

Warsaw, Masovian District, Poland

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