Clinical trial NCT05716880: Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome
Official title: FORMA - a Multicenter Randomized-controlled Trial to Evaluate the Efficacy and Safety of Ketoanalogues of Essential Amino Acids in Prophylaxis of Protein-energy Wasting in Nephrotic Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Nephrotic Syndrome
Keywords: nephrotic syndrome
protein-energy wasting
neph-PEW
lean tissue mass
Ketosteril
ketoanalogues
Lead sponsor: Military Institute od Medicine National Research Institute
Sponsor class: OTHER
Collaborators: name: Medical University of Lodz
name: Medical University of Warsaw
First posted: 2023-02-08
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization in 1:1 ratio with stratification by the type of glomerular disease (podocytopathy versus other type) and investigational site
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum loss of lean tissue mass
timeFrame: 6 months
Secondary outcomes:
measure: Maximum loss of lean tissue mass
timeFrame: 6 months
measure: Neph-PEW diagnosis
timeFrame: 6 months
measure: 6-minute walk test distance
timeFrame: 6 months
measure: Handgrip strength (HGS)
timeFrame: 6 months
measure: Serum albumin
timeFrame: 6 months
measure: Urinary protein/creatinine ratio (uPCR)
timeFrame: 6 months
measure: Low density lipoprotein (LDL)
timeFrame: 6 months
measure: Triglycerides
timeFrame: 6 months
measure: Uric acid
timeFrame: 6 months
measure: Unfavorable disease course
timeFrame: 12 months
measure: Glomerular filtration rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine - National Research Institute
state: Masovian District
Study officials:
affiliation: Military Institute of Medicine - National Research Institute
name: Anna Matyjek
role: STUDY_CHAIR
References:
citation: Matyjek A, Literacki S, Niemczyk S, Rymarz A. Protein energy-wasting associated with nephrotic syndrome - the comparison of metabolic pattern in severe nephrosis to different stages of chronic kidney disease. BMC Nephrol. 2020 Aug 14;21(1):346. doi: 10.1186/s12882-020-02003-4.
citation: Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021. No abstract available.
citation: Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, Franch H, Guarnieri G, Ikizler TA, Kaysen G, Lindholm B, Massy Z, Mitch W, Pineda E, Stenvinkel P, Trevino-Becerra A, Wanner C. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 2008 Feb;73(4):391-8. doi: 10.1038/sj.ki.5002585. Epub 2007 Dec 19.
citation: Kaysen GA, Gambertoglio J, Jimenez I, Jones H, Hutchison FN. Effect of dietary protein intake on albumin homeostasis in nephrotic patients. Kidney Int. 1986 Feb;29(2):572-7. doi: 10.1038/ki.1986.36.
citation: Barsotti G, Morelli E, Cupisti A, Bertoncini P, Giovannetti S. A special, supplemented 'vegan' diet for nephrotic patients. Am J Nephrol. 1991;11(5):380-5. doi: 10.1159/000168342.