Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Ketosteril
  Daily dose = 1 tabl / 5 kg of ideal body weight
• Другое Medium Protein Diet (MPD)
  MPD: daily protein intake of 0.8-1.0 g/kg of ideal body weight + up to 5 g based on daily proteinuria

Первичные конечные точки

• Maximum loss of lean tissue mass [Срок оценки: 6 months]

Вторичные конечные точки (11)

• Maximum loss of lean tissue mass [Срок оценки: 6 months]
• Neph-PEW diagnosis [Срок оценки: 6 months]
• 6-minute walk test distance [Срок оценки: 6 months]
• Handgrip strength (HGS) [Срок оценки: 6 months]
• Serum albumin [Срок оценки: 6 months]
• Urinary protein/creatinine ratio (uPCR) [Срок оценки: 6 months]
• Low density lipoprotein (LDL) [Срок оценки: 6 months]
• Triglycerides [Срок оценки: 6 months]
• Uric acid [Срок оценки: 6 months]
• Unfavorable disease course [Срок оценки: 12 months]
• Glomerular filtration rate [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Поддерживающая терапия

Центры проведения

Польша · 1 центр

• Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine - — Warsaw

Публикации

• 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. PMID 32795277
• 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. PMID 34556256
• 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. PMID 18094682
• 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. PMID 3702214
• 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. PMID 1809035

Идентификаторы

NCT: NCT05716880 · ABM/FORMA/2021 · 2022-000529-26 · 2021/ABM/01/00036-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗