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Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome (FORMA)

Primary Purpose

Nephrotic Syndrome

Status
Recruiting
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
Ketosteril
Medium Protein Diet (MPD)
Sponsored by
Military Institute od Medicine National Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Nephrotic Syndrome focused on measuring nephrotic syndrome, protein-energy wasting, neph-PEW, lean tissue mass, Ketosteril, ketoanalogues

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

KA+MPD

MPD

Arm Description

Ketosteril + Medium Protein Diet (MPD) for 12 months

Medium Protein Diet (MPD) for 12 months

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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-minute walk test distance
Change in distance walked in the 6-minute walk test from baseline value; expressed in meters.
Handgrip strength (HGS)
Change in HGS value from baseline; expressed in kg.
Serum albumin
Change in serum albumin level from baseline value; expressed in g/dL.
Urinary protein/creatinine ratio (uPCR)
Change in uPCR value from baseline; expressed in mg/g.
Low density lipoprotein (LDL)
Change in serum LDL level from baseline; expressed in mg/dL.
Triglycerides
Change in serum triglycerides level from baseline; expressed in mg/dL.
Uric acid
Change in serum uric acid level from baseline; expressed in mg/dL.
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.
Glomerular filtration rate
Change in glomerular filtration rate from baseline; expressed in mL/min/1.73m2.

Full Information

First Posted
January 30, 2023
Last Updated
January 30, 2023
Sponsor
Military Institute od Medicine National Research Institute
Collaborators
Medical University of Lodz, Medical University of Warsaw
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1. Study Identification

Unique Protocol Identification Number
NCT05716880
Brief Title
Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome
Acronym
FORMA
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

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 3, 2023 (Actual)
Primary Completion Date
February 28, 2027 (Anticipated)
Study Completion Date
August 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Military Institute od Medicine National Research Institute
Collaborators
Medical University of Lodz, Medical University of Warsaw

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephrotic Syndrome
Keywords
nephrotic syndrome, protein-energy wasting, neph-PEW, lean tissue mass, Ketosteril, ketoanalogues

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomization in 1:1 ratio with stratification by the type of glomerular disease (podocytopathy versus other type) and investigational site
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
KA+MPD
Arm Type
Experimental
Arm Description
Ketosteril + Medium Protein Diet (MPD) for 12 months
Arm Title
MPD
Arm Type
Active Comparator
Arm Description
Medium Protein Diet (MPD) for 12 months
Intervention Type
Drug
Intervention Name(s)
Ketosteril
Intervention Description
Daily dose = 1 tabl / 5 kg of ideal body weight
Intervention Type
Other
Intervention Name(s)
Medium Protein Diet (MPD)
Intervention Description
MPD: daily protein intake of 0.8-1.0 g/kg of ideal body weight + up to 5 g based on daily proteinuria
Primary Outcome Measure Information:
Title
Maximum loss of lean tissue mass
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Maximum loss of lean tissue mass
Description
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.
Time Frame
6 months
Title
Neph-PEW diagnosis
Description
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.
Time Frame
6 months
Title
6-minute walk test distance
Description
Change in distance walked in the 6-minute walk test from baseline value; expressed in meters.
Time Frame
6 months
Title
Handgrip strength (HGS)
Description
Change in HGS value from baseline; expressed in kg.
Time Frame
6 months
Title
Serum albumin
Description
Change in serum albumin level from baseline value; expressed in g/dL.
Time Frame
6 months
Title
Urinary protein/creatinine ratio (uPCR)
Description
Change in uPCR value from baseline; expressed in mg/g.
Time Frame
6 months
Title
Low density lipoprotein (LDL)
Description
Change in serum LDL level from baseline; expressed in mg/dL.
Time Frame
6 months
Title
Triglycerides
Description
Change in serum triglycerides level from baseline; expressed in mg/dL.
Time Frame
6 months
Title
Uric acid
Description
Change in serum uric acid level from baseline; expressed in mg/dL.
Time Frame
6 months
Title
Unfavorable disease course
Description
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.
Time Frame
12 months
Title
Glomerular filtration rate
Description
Change in glomerular filtration rate from baseline; expressed in mL/min/1.73m2.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Matyjek, MD, PhD
Phone
261817045
Ext
+48
Email
amatyjek@wim.mil.pl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna Matyjek
Organizational Affiliation
Military Institute of Medicine - National Research Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine - National Research Institute
City
Warsaw
State/Province
Masovian District
ZIP/Postal Code
04-141
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Matyjek, MD, PhD
Phone
261817045
Ext
+48
Email
amatyjek@wim.mil.pl
First Name & Middle Initial & Last Name & Degree
Stanislaw Niemczyk, MD, PhD, Prof.

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32795277
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.
Results Reference
background
PubMed Identifier
34556256
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.
Results Reference
background
PubMed Identifier
18094682
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. Erratum In: Kidney Int. 2008 Aug;74(3):393. Trevinho-Becerra, A [corrected to Trevino-Becerra, A].
Results Reference
background
PubMed Identifier
3702214
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.
Results Reference
background
PubMed Identifier
1809035
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.
Results Reference
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Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome

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