FORMA: Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome

Sponsor

Military Institute of Medicine, Poland (Other)

Overall Status

Recruiting

CT.gov ID

NCT05716880

Collaborator

Medical University of Lodz (Other), Medical University of Warsaw (Other)

150

Enrollment

Location

Arms

55.9

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Nephrotic Syndrome	Drug: Ketosteril Other: Medium Protein Diet (MPD)	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomization in 1:1 ratio with stratification by the type of glomerular disease (podocytopathy versus other type) and investigational siteRandomization in 1:1 ratio with stratification by the type of glomerular disease (podocytopathy versus other type) and investigational site

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

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

Actual Study Start Date :

Jan 3, 2023

Anticipated Primary Completion Date :

Feb 28, 2027

Anticipated Study Completion Date :

Aug 31, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Maximum loss of lean tissue mass [6 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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine - National Research Institute	Warsaw	Masovian District	Poland	04-141