Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome (FORMA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Nephrotic Syndrome
• Intervention / Treatment: Drug: Ketosteril; Other: Medium Protein Diet (MPD)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anna Matyjek, MD, PhD; Phone Number: +48 261817045; Email: amatyjek@wim.mil.pl

Study Locations

• Poland
  • Masovian District
    • Warsaw, Masovian District, Poland, 04-141
      • Recruiting
      • Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine - National Research Institute
      • Contact: Anna Matyjek, MD, PhD; Phone Number: +48 261817045; Email: amatyjek@wim.mil.pl
      • Principal Investigator: Stanislaw Niemczyk, MD, PhD, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: KA+MPD; Ketosteril + Medium Protein Diet (MPD) for 12 months	Drug: Ketosteril; Daily dose = 1 tabl / 5 kg of ideal body weight; Other: 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
ACTIVE_COMPARATOR: MPD; Medium Protein Diet (MPD) for 12 months	Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum loss of lean tissue mass	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum loss of lean tissue mass	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.	6 months
Neph-PEW diagnosis	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.	6 months
6-minute walk test distance	Change in distance walked in the 6-minute walk test from baseline value; expressed in meters.	6 months
Handgrip strength (HGS)	Change in HGS value from baseline; expressed in kg.	6 months
Serum albumin	Change in serum albumin level from baseline value; expressed in g/dL.	6 months
Urinary protein/creatinine ratio (uPCR)	Change in uPCR value from baseline; expressed in mg/g.	6 months
Low density lipoprotein (LDL)	Change in serum LDL level from baseline; expressed in mg/dL.	6 months
Triglycerides	Change in serum triglycerides level from baseline; expressed in mg/dL.	6 months
Uric acid	Change in serum uric acid level from baseline; expressed in mg/dL.	6 months
Unfavorable disease course	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.	12 months
Glomerular filtration rate	Change in glomerular filtration rate from baseline; expressed in mL/min/1.73m2.	12 months

Collaborators and Investigators

• Sponsor: Military Institute of Medicine, Poland
• Collaborators: Medical University of Lodz; Medical University of Warsaw
• Investigators: Study Chair: Anna Matyjek, Military Institute of Medicine - National Research Institute

Publications and helpful links

General Publications

• 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.
• 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.
• 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. Erratum In: Kidney Int. 2008 Aug;74(3):393. Trevinho-Becerra, A [corrected to Trevino-Becerra, A].
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 3, 2023
• Primary Completion (ANTICIPATED): February 28, 2027
• Study Completion (ANTICIPATED): August 31, 2027

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: January 30, 2023
• First Posted (ACTUAL): February 8, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: January 30, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Ketosteril; ketoanalogues; nephrotic syndrome; protein-energy wasting; neph-PEW; lean tissue mass
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis
• Other Study ID Numbers: ABM/FORMA/2021; 2022-000529-26 (EUDRACT_NUMBER); 2021/ABM/01/00036-00 (OTHER_GRANT: Medical Research Agency, Poland)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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