Nephrotic Syndrome Steroid-DependentPRECISENCT06792448
Biomarkers and Outcome Predictors of Pediatric Nephrotic Syndrome: A Genetic, Transcriptomic, and Secretome Multiomics Study
An observational study of Nephrotic Syndrome Steroid-Dependent and Nephrotic Syndrome Steroid-Resistant, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico.
Trial summary
Idiopathic Nephrotic Syndrome is a rare disease of the kidneys, which typically affects children. For most affected children there is the need of a prolonged treatment with drugs reducing the activity of the immune system, also resulting in many side effects. Read more about this study
- Who is it for?
- Ages Up to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Nephrotic Syndrome Steroid-Dependent, Nephrotic Syndrome Steroid-Resistant, Nephrotic Syndrome in Children
- How many people
- 350 participants
- Where
- No sites listed yet
- Study dates
- 15 Feb 2025to 1 Jun 2028
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: The study participants will be selected from a population of pediatric patients with idiopathic nephrotic syndrome (INS) who are treatment-naive and present with clinical symptoms such as proteinuria, hypoalbuminemia, and edema. These patients, aged 1 to 18 years, are typically referred to specialized nephrology clinics or tertiary care centers across Europe, where they receive initial diagnosis and follow-up care. The participant pool is drawn from both primary recruiting centers, which are large pediatric nephrology units with established expertise in managing nephrotic syndrome, and additional collaborating centers within the European ERKNet and ESCAPE Networks. This setting ensures a broad representation of pediatric INS cases across various European regions, enhancing the study's generalizability. Additionally, a control group of age-matched children without nephrotic syndrome is included, selected from children undergoing minor urological procedures in these clinical settings.
Who may be able to join
- Clinical diagnosis of idiopathic nephrotic syndrome (INS) with nephrotic range proteinuria (uPr/uCr ratio > 2 mg/mg).
- Hypoalbuminemia with serum albumin < 3.0 g/dL.
- Presence of edema.
- No prior treatment for idiopathic nephrotic syndrome.
- Age between 1 and 18 years at the time of enrollment.
- igned informed consent by a parent or legal guardian.
Who cannot join
- Diagnosis of congenital or infantile nephrotic syndrome (age < 1 year).
- Diagnosis of secondary nephrotic syndrome.
- Presence of glomerulonephritis, autoimmune diseases, or vasculitis.
- Lack of signed informed consent by a parent or legal guardian.
- Previous treatment with prednisone or prednisolone for nephrotic syndrome.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Idiopathic Nephrotic Syndrome is a rare disease of the kidneys, which typically affects children. For most affected children there is the need of a prolonged treatment with drugs reducing the activity of the immune system, also resulting in many side effects. Those patients, who do not respond to treatment, are at risk of kidney damage and of dialysis or kidney transplantation. It is currently impossible to predict the response to treatment, leading to unnecessary therapies with side effects as well as unclear prognosis in the affected children. The response of the idiopathic nephrotic syndrome to medications acting on the immune system explains its important role in the occurrence of the disease.
With this study we aim to obtain predictors of the response to treatment right at the beginning of the disease, to adapt the therapy avoiding needless side effects. This will be done evaluating the blood and urine of affected children using state of the art molecular characterisation. We will evaluate the genetic predisposition, the cell trait changes and the presence of molecules in blood and urine that may affect the interaction between the immune system and the kidneys. We expect that the findings will improve treatment of children with idiopathic nephrotic syndrome and reduce the number of children suffering from unnecessary drugs related side effects.
Read the detailed description
The PRECISE study (Biomarkers and Outcome Predictors of Pediatric Nephrotic Syndrome) is an innovative, multicenter research project focused on advancing our understanding of pediatric nephrotic syndrome (NS) and improving treatment outcomes for affected children across Europe. This project, which involves multiple European institutions, centers around discovering predictive biomarkers using advanced genetic, transcriptomic, and secretome multiomics methods. Nephrotic syndrome, a complex kidney disease that primarily impacts children, can lead to significant health challenges and often necessitates prolonged treatment with immunosuppressive drugs that carry side effects.
Overview of Nephrotic Syndrome
Nephrotic syndrome is characterized by symptoms such as proteinuria (excessive protein in the urine), hypoalbuminemia (low blood albumin levels), edema (swelling), and hyperlipidemia (high blood lipids). Pediatric nephrotic syndrome, known for its unpredictable nature, is categorized as Idiopathic Nephrotic Syndrome (INS) and affects around 2-7 children per 100,000 each year. While some children respond well to steroid treatment (steroid-sensitive), a significant proportion may become steroid-resistant, risking severe kidney damage that may lead to dialysis or even kidney transplant.
Why This Study is Important
Currently, it is challenging to predict which children will respond to treatment, how their disease will progress, or which children may experience repeated relapses. The standard treatment with immunosuppressive drugs, although effective for some, can bring numerous side effects, especially with prolonged use. Therefore, one of the most pressing unmet needs in pediatric nephrology is to develop early predictive biomarkers for individualized treatment plans, ultimately reducing unnecessary drug exposure and improving long-term outcomes.
The PRECISE study is designed to fill this critical gap by identifying genetic and molecular markers that can help clinicians:
- Predict Treatment Response - Identify children who may or may not respond to steroid therapy.
- Anticipate Disease Progression - Understand which patients are more likely to experience relapses or progress toward kidney failure.
- Personalize Therapy - Tailor treatments based on each patient's unique biological profile to minimize side effects and maximize effectiveness.
Objectives of the Study
The primary goal of the PRECISE study is to create a predictive model for differentiating children with Steroid-Resistant Nephrotic Syndrome (SRNS) or Steroid-Dependent Nephrotic Syndrome (SDNS) from those with Infrequent Relapsing Nephrotic Syndrome (IRNS) right at the onset of the disease. This model will integrate various data sources, including omics, genetic, and clinical information, to produce a reliable "biomarker signature" that can guide therapeutic decisions from the start.
The study has several secondary objectives, including:
- Genetic and Epigenetic Analysis - Identifying the genetic and epigenetic factors that contribute to nephrotic syndrome's pathogenesis.
- Immune System Profiling - Understanding how adaptive immune system alterations may influence disease onset and progression.
- Molecular Characterization - Using advanced proteomics to identify distinct protein patterns in serum and urine that differ between disease subtypes.
- Healthy Controls Comparison - Analyzing the molecular characteristics of healthy children to enhance the accuracy of disease-specific biomarkers.
Study Design and Methodology
The PRECISE study is an open, multicenter, observational study. It will enroll a total of 310 children diagnosed with INS and an additional control group of 40 healthy children. The study is structured as follows:
- Discovery Phase - This phase will involve 110 treatment-naive children with INS who will be followed for 12 months. During this period, biological samples will be collected at several key points, such as at the time of diagnosis, during remission, and in case of relapse. These samples will undergo extensive molecular profiling, including genetic, proteomic, and transcriptomic analyses, which will enable the identification of key biomarkers.
- Validation Phase - In this phase, an independent cohort of 200 INS patients (prevalent cases) will be studied to confirm the reliability of biomarkers identified in the discovery phase.
Key Elements of the Study Protocol
Inclusion Criteria for Participants
For the main study group, children must be aged between 1 and 18 years and have a clinical diagnosis of idiopathic nephrotic syndrome. They should not have undergone any previous treatment for INS and must meet specific criteria for disease markers, such as proteinuria and hypoalbuminemia. A validation cohort includes children with similar characteristics but who have already been treated, while a control group comprises healthy children with no proteinuria and minor congenital kidney conditions.
Data Collection and Sampling
At each assessment visit, clinical data will be gathered, including physical exam results, medical history, vital signs, and laboratory values. Biological samples (blood and urine) will also be collected and stored at centralized biobanking facilities, with samples being analyzed for a wide range of molecular markers. The study uses high-level biostatistics and bioinformatics to interpret the complex data, aiming to provide a multidimensional view of each participant's health profile.
Analysis and Expected Outcomes
Using advanced statistical techniques and machine learning algorithms, researchers will analyze differences in genetic, immune, and molecular markers among the different patient groups. The primary endpoint is to develop molecular signatures predictive of disease progression, which can differentiate between SRNS, SDNS, and IRNS groups. Secondary endpoints include:
- Genetic Predispositions - Assessing variants in immune- and kidney-related genes that may be associated with disease progression.
- Immune Alterations - Evaluating specific immune cell types and their behaviors, which may be linked to the risk of relapse or resistance to treatment.
- Proteomic Profiles - Identifying protein patterns in blood and urine that are unique to the disease and could be used to classify disease stages and predict outcomes.
Impact and Implications
The PRECISE study represents a major step forward in pediatric nephrology by leveraging cutting-edge scientific methods to address the pressing challenges faced by children with nephrotic syndrome. By identifying biomarkers that predict treatment response and disease progression, this study can help tailor treatments to each child's needs, reducing the risk of adverse side effects and improving overall outcomes.
Consortium and Collaborating Institutions
The project is led by the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy, under the guidance of Principal Investigator Prof. Giovanni Montini. It brings together several renowned research centers and universities across Europe, each contributing unique expertise in pediatric nephrology, genetics, and molecular biology. Key partners include Heidelberg University, University Hospital of Cologne, Medical University of Gdansk, Istanbul University, and Vilnius University, along with patient advocacy organizations such as NephCEurope and various national nephrology groups.
Through this consortium, the study integrates expertise and resources from across Europe, ensuring a robust and comprehensive approach to this challenging area of pediatric medicine.
Summary
In summary, the PRECISE study is a pioneering effort to improve the diagnosis, prognosis, and treatment of pediatric nephrotic syndrome through the identification of precise molecular biomarkers. This study not only seeks to benefit children affected by nephrotic syndrome today but also lays the groundwork for future research in rare kidney diseases. By aligning clinical care with the latest in genetic and molecular science, the PRECISE study aims to provide new hope to families affected by this chronic and often debilitating condition.
- Conditions
- Nephrotic Syndrome Steroid-Dependent, Nephrotic Syndrome Steroid-Resistant, Nephrotic Syndrome in Children, Glomerulonephritis, Proteinuria, Hypoalbuminemia
- Keywords
- Pediatric nephrotic syndrome, Idiopathic nephrotic syndrome, Steroid-resistant nephrotic syndrome, Steroid-sensitive nephrotic syndrome, Biomarkers discovery, Genetic risk factors, Epigenetic analysis, Adaptive immune system profiling, Liquid biopsy, Serum and urine proteomics, Multiomics approach, Personalized treatment, Disease progression prediction, Molecular characterization, Pediatric kidney disease
- Medical subject headings
- Nephrotic Syndrome, Glomerulonephritis, Proteinuria, Hypoalbuminemia, Kidney Diseases, Renal Insufficiency, Chronic, Nephrosis, Lipoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Treatment-Naive Idiopathic Nephrotic Syndrome (INS) Patients | This cohort comprises 110 children diagnosed with idiopathic nephrotic syndrome (INS) who are treatment-naive at enrollment. The participants will receive a standard induction therapy with prednisone or prednisolone and will be followed for 12 months. During this period, blood and urine samples will be collected at various points (enrollment, 6 weeks, 6 months, and 12 months) and in cases of relapse. The goal is to monitor disease progression and classify patients based on their response to therapy, specifically identifying subtypes such as steroid-resistant, steroid-dependent, and infrequent relapsing nephrotic syndrome . | |
| Healthy Pediatric Control Group | This cohort consists of 40 age-matched children without nephrotic syndrome, selected from individuals undergoing minor urological surgical procedures. These participants will provide baseline control samples (blood and urine) for comparison with the INS patients' samples. This group allows researchers to identify molecular characteristics unique to INS by contrasting them with data from healthy children . | |
| Prevalent Idiopathic Nephrotic Syndrome (INS) Patients | This group includes 200 INS patients who have previously received treatment and are part of the larger validation phase. This cohort will be used to confirm the biomarkers and molecular profiles identified in the main cohort. The aim is to generalize findings and ensure that identified biomarkers are consistent across a broader population. Samples will be collected during relapse and remission, aligning with the study's focus on validating predictive biomarkers of disease course and therapeutic response . |
What is being measured
The primary outcome is the main question the study is designed to answer.
Predictive Molecular Signature of INS Progression
Identification of distinct molecular characteristics predictive of the progression of idiopathic nephrotic syndrome (INS). This includes differentiating between steroid-resistant nephrotic syndrome (SRNS), steroid-dependent nephrotic syndrome (SDNS), and infrequent relapsing nephrotic syndrome (IRNS).
Measure Type: Analysis of genetic/epigenetic background, immune status, and vesicular proteome/transcriptomic profile.
Goal: Develop a biomarker-based predictive model that assists in early classification of INS subtypes.
Measured: Up to 1 year from enrollment after initial diagnosis.
Secondary outcomes (4)
Genetic and Epigenetic Risk Factors
Quantification of kidney- and immune-related genetic variants associated with INS incidence and disease progression.
Measure Type: Number of risk variants in kidney and immune-related genes, along with methylation profiles showing hypomethylated and hypermethylated regions related to immune function and progression to kidney failure .
Measured: Up to 6 months from enrollment after initial diagnosis.
Immune System Alterations
Analysis of adaptive immune system changes in INS patients. Measure Type: Proportion and absolute numbers of B and T cell subpopulations, changes in immune cell subset genes, and phosphorylation sites in primary immune cells.
Goal: Examine immune profiles associated with disease subtypes to better understand immunologic drivers of INS .
Measured: Up to 1 year from enrollment after initial diagnosis.
Proteomic Patterns in Serum and Urine
Identification of unique protein profiles in serum and urine that correlate with different INS subtypes.
Measure Type: Analysis of extracellular vesicle concentration and size in urine, surface proteome of extracellular vesicles, and serum proteome characteristics in different INS groups.
Goal: Detect specific proteomic markers linked to disease phenotype and progression .
Measured: Up to 1 year from enrollment after initial diagnosis.
Molecular Profile of Healthy Control Group
Comprehensive molecular characterization of healthy children to establish a baseline for comparison with INS patients.
Measure Type: Similar profiling as for INS patients, focusing on genetic and proteomic markers.
Goal: Differentiate between disease-specific and baseline molecular signatures .
Measured: At a single time point during enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2025
- Study start15 Feb 2025 (estimated)
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nephrotic Syndrome Steroid-DependentStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 350 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione La Nuova Speranza ONLUS, ASSOCIAZIONE SINDROME NEFROSICA ITALIA, Nephie e.V., NephCEurope, European Joint Programme on Rare Diseases (EJP RD JTC 2023), ERKNet
- Responsible party
- Sponsor
- Investigators
- Giovanni Montini, Doctor of Medicine, Principal investigator, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06792448
- Sponsor's protocol ID
- 5244_11.09.2024_P
- Other IDs
- EJPRD23-108
- Acronym
- PRECISE
- Status last verified
- Nov 2024
- First submitted
- 11 Dec 2024
- Last updated
- 30 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The PRECISE study does not plan to share Individual Participant Data (IPD). This decision prioritizes the protection of participant confidentiality and aligns with the study's ethical guidelines, ensuring that sensitive genetic, transcriptomic, and proteomic information remains secure. As such, no IPD collected throughout the trial will be made available publicly or for secondary research purposes.
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers and Outcome Predictors of Pediatric Nephrotic Syndrome: A Genetic, Transcriptomic, and Secretome Multiomics Study
- ClinicalTrials.gov ID
- NCT06792448
- Acronym / sponsor ID
- PRECISE / 5244_11.09.2024_P
- Conditions
- Nephrotic Syndrome Steroid-Dependent, Nephrotic Syndrome Steroid-Resistant, Nephrotic Syndrome in Children, Glomerulonephritis, Proteinuria, Hypoalbuminemia
- Keywords
- Pediatric nephrotic syndrome, Idiopathic nephrotic syndrome, Steroid-resistant nephrotic syndrome, Steroid-sensitive nephrotic syndrome, Biomarkers discovery, Genetic risk factors, Epigenetic analysis, Adaptive immune system profiling
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Collaborators
- Fondazione La Nuova Speranza ONLUS, ASSOCIAZIONE SINDROME NEFROSICA ITALIA, Nephie e.V., NephCEurope, European Joint Programme on Rare Diseases (EJP RD JTC 2023), ERKNet
- Study start
- 15 Feb 2025 (estimated)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 24 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Idiopathic Nephrotic Syndrome is a rare disease of the kidneys, which typically affects children. For most affected children there is the need of a prolonged treatment with drugs reducing the activity of the immune system, also resulting in many side effects. Those patients, who do not respond to treatment, are at risk of kidney damage and of dialysis or kidney transplantation. It is currently impossible to predict the response to treatment, leading to unnecessary therapies with side effects as well as unclear prognosis in the affected children. The response of the idiopathic nephrotic syndrome to medications acting on the immune system explains its important role in the occurrence of the disease.
With this study we aim to obtain predictors of the response to treatment right at the beginning of the disease, to adapt the therapy avoiding needless side effects. This will be done evaluating the blood and urine of affected children using state of the art molecular characterisation. We will evaluate the genetic predisposition, the cell trait changes and the presence of molecules in blood and urine that may affect the interaction between the immune system and the kidneys. We expect that the findings will improve treatment of children with idiopathic nephrotic syndrome and reduce the number of children suffering from unnecessary drugs related side effects.
Detailed description
The PRECISE study (Biomarkers and Outcome Predictors of Pediatric Nephrotic Syndrome) is an innovative, multicenter research project focused on advancing our understanding of pediatric nephrotic syndrome (NS) and improving treatment outcomes for affected children across Europe. This project, which involves multiple European institutions, centers around discovering predictive biomarkers using advanced genetic, transcriptomic, and secretome multiomics methods. Nephrotic syndrome, a complex kidney disease that primarily impacts children, can lead to significant health challenges and often necessitates prolonged treatment with immunosuppressive drugs that carry side effects.
Overview of Nephrotic Syndrome
Nephrotic syndrome is characterized by symptoms such as proteinuria (excessive protein in the urine), hypoalbuminemia (low blood albumin levels), edema (swelling), and hyperlipidemia (high blood lipids). Pediatric nephrotic syndrome, known for its unpredictable nature, is categorized as Idiopathic Nephrotic Syndrome (INS) and affects around 2-7 children per 100,000 each year. While some children respond well to steroid treatment (steroid-sensitive), a significant proportion may become steroid-resistant, risking severe kidney damage that may lead to dialysis or even kidney transplant.
Why This Study is Important
Currently, it is challenging to predict which children will respond to treatment, how their disease will progress, or which children may experience repeated relapses. The standard treatment with immunosuppressive drugs, although effective for some, can bring numerous side effects, especially with prolonged use. Therefore, one of the most pressing unmet needs in pediatric nephrology is to develop early predictive biomarkers for individualized treatment plans, ultimately reducing unnecessary drug exposure and improving long-term outcomes.
The PRECISE study is designed to fill this critical gap by identifying genetic and molecular markers that can help clinicians:
- Predict Treatment Response - Identify children who may or may not respond to steroid therapy.
- Anticipate Disease Progression - Understand which patients are more likely to experience relapses or progress toward kidney failure.
- Personalize Therapy - Tailor treatments based on each patient's unique biological profile to minimize side effects and maximize effectiveness.
Objectives of the Study
The primary goal of the PRECISE study is to create a predictive model for differentiating children with Steroid-Resistant Nephrotic Syndrome (SRNS) or Steroid-Dependent Nephrotic Syndrome (SDNS) from those with Infrequent Relapsing Nephrotic Syndrome (IRNS) right at the onset of the disease. This model will integrate various data sources, including omics, genetic, and clinical information, to produce a reliable "biomarker signature" that can guide therapeutic decisions from the start.
The study has several secondary objectives, including:
- Genetic and Epigenetic Analysis - Identifying the genetic and epigenetic factors that contribute to nephrotic syndrome's pathogenesis.
- Immune System Profiling - Understanding how adaptive immune system alterations may influence disease onset and progression.
- Molecular Characterization - Using advanced proteomics to identify distinct protein patterns in serum and urine that differ between disease subtypes.
- Healthy Controls Comparison - Analyzing the molecular characteristics of healthy children to enhance the accuracy of disease-specific biomarkers.
Study Design and Methodology
The PRECISE study is an open, multicenter, observational study. It will enroll a total of 310 children diagnosed with INS and an additional control group of 40 healthy children. The study is structured as follows:
- Discovery Phase - This phase will involve 110 treatment-naive children with INS who will be followed for 12 months. During this period, biological samples will be collected at several key points, such as at the time of diagnosis, during remission, and in case of relapse. These samples will undergo extensive molecular profiling, including genetic, proteomic, and transcriptomic analyses, which will enable the identification of key biomarkers.
- Validation Phase - In this phase, an independent cohort of 200 INS patients (prevalent cases) will be studied to confirm the reliability of biomarkers identified in the discovery phase.
Key Elements of the Study Protocol
Inclusion Criteria for Participants
For the main study group, children must be aged between 1 and 18 years and have a clinical diagnosis of idiopathic nephrotic syndrome. They should not have undergone any previous treatment for INS and must meet specific criteria for disease markers, such as proteinuria and hypoalbuminemia. A validation cohort includes children with similar characteristics but who have already been treated, while a control group comprises healthy children with no proteinuria and minor congenital kidney conditions.
Data Collection and Sampling
At each assessment visit, clinical data will be gathered, including physical exam results, medical history, vital signs, and laboratory values. Biological samples (blood and urine) will also be collected and stored at centralized biobanking facilities, with samples being analyzed for a wide range of molecular markers. The study uses high-level biostatistics and bioinformatics to interpret the complex data, aiming to provide a multidimensional view of each participant's health profile.
Analysis and Expected Outcomes
Using advanced statistical techniques and machine learning algorithms, researchers will analyze differences in genetic, immune, and molecular markers among the different patient groups. The primary endpoint is to develop molecular signatures predictive of disease progression, which can differentiate between SRNS, SDNS, and IRNS groups. Secondary endpoints include:
- Genetic Predispositions - Assessing variants in immune- and kidney-related genes that may be associated with disease progression.
- Immune Alterations - Evaluating specific immune cell types and their behaviors, which may be linked to the risk of relapse or resistance to treatment.
- Proteomic Profiles - Identifying protein patterns in blood and urine that are unique to the disease and could be used to classify disease stages and predict outcomes.
Impact and Implications
The PRECISE study represents a major step forward in pediatric nephrology by leveraging cutting-edge scientific methods to address the pressing challenges faced by children with nephrotic syndrome. By identifying biomarkers that predict treatment response and disease progression, this study can help tailor treatments to each child's needs, reducing the risk of adverse side effects and improving overall outcomes.
Consortium and Collaborating Institutions
The project is led by the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy, under the guidance of Principal Investigator Prof. Giovanni Montini. It brings together several renowned research centers and universities across Europe, each contributing unique expertise in pediatric nephrology, genetics, and molecular biology. Key partners include Heidelberg University, University Hospital of Cologne, Medical University of Gdansk, Istanbul University, and Vilnius University, along with patient advocacy organizations such as NephCEurope and various national nephrology groups.
Through this consortium, the study integrates expertise and resources from across Europe, ensuring a robust and comprehensive approach to this challenging area of pediatric medicine.
Summary
In summary, the PRECISE study is a pioneering effort to improve the diagnosis, prognosis, and treatment of pediatric nephrotic syndrome through the identification of precise molecular biomarkers. This study not only seeks to benefit children affected by nephrotic syndrome today but also lays the groundwork for future research in rare kidney diseases. By aligning clinical care with the latest in genetic and molecular science, the PRECISE study aims to provide new hope to families affected by this chronic and often debilitating condition.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment-Naive Idiopathic Nephrotic Syndrome (INS) Patients | – | –This cohort comprises 110 children diagnosed with idiopathic nephrotic syndrome (INS) who are treatment-naive at enrollment. The participants will receive a standard induction therapy with prednisone or prednisolone and will be followed for 12 months. During this period, blood and urine samples will be collected at various points (enrollment, 6 weeks, 6 months, and 12 months) and in cases of relapse. The goal is to monitor disease progression and classify patients based on their response to therapy, specifically identifying subtypes such as steroid-resistant, steroid-dependent, and infrequent relapsing nephrotic syndrome . |
| Healthy Pediatric Control Group | – | –This cohort consists of 40 age-matched children without nephrotic syndrome, selected from individuals undergoing minor urological surgical procedures. These participants will provide baseline control samples (blood and urine) for comparison with the INS patients' samples. This group allows researchers to identify molecular characteristics unique to INS by contrasting them with data from healthy children . |
| Prevalent Idiopathic Nephrotic Syndrome (INS) Patients | – | –This group includes 200 INS patients who have previously received treatment and are part of the larger validation phase. This cohort will be used to confirm the biomarkers and molecular profiles identified in the main cohort. The aim is to generalize findings and ensure that identified biomarkers are consistent across a broader population. Samples will be collected during relapse and remission, aligning with the study's focus on validating predictive biomarkers of disease course and therapeutic response . |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- The study participants will be selected from a population of pediatric patients with idiopathic nephrotic syndrome (INS) who are treatment-naive and present with clinical symptoms such as proteinuria, hypoalbuminemia, and edema. These patients, aged 1 to 18 years, are typically referred to specialized nephrology clinics or tertiary care centers across Europe, where they receive initial diagnosis and follow-up care. The participant pool is drawn from both primary recruiting centers, which are large pediatric nephrology units with established expertise in managing nephrotic syndrome, and additional collaborating centers within the European ERKNet and ESCAPE Networks. This setting ensures a broad representation of pediatric INS cases across various European regions, enhancing the study's generalizability. Additionally, a control group of age-matched children without nephrotic syndrome is included, selected from children undergoing minor urological procedures in these clinical settings.
Key inclusion criteria (6 listed)
- Clinical diagnosis of idiopathic nephrotic syndrome (INS) with nephrotic range proteinuria (uPr/uCr ratio > 2 mg/mg).
- Hypoalbuminemia with serum albumin < 3.0 g/dL.
- Presence of edema.
- No prior treatment for idiopathic nephrotic syndrome.
- Age between 1 and 18 years at the time of enrollment.
Key exclusion criteria (5 listed)
- Diagnosis of congenital or infantile nephrotic syndrome (age < 1 year).
- Diagnosis of secondary nephrotic syndrome.
- Presence of glomerulonephritis, autoimmune diseases, or vasculitis.
- Lack of signed informed consent by a parent or legal guardian.
- Previous treatment with prednisone or prednisolone for nephrotic syndrome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Predictive Molecular Signature of INS Progression
Time frame: Up to 1 year from enrollment after initial diagnosis.
Identification of distinct molecular characteristics predictive of the progression of idiopathic nephrotic syndrome (INS). This includes differentiating between steroid-resistant nephrotic syndrome (SRNS), steroid-dependent nephrotic syndrome (SDNS), and infrequent relapsing nephrotic syndrome (IRNS). Measure Type: Analysis of genetic/epigenetic background, immune status, and vesicular proteome/transcriptomic profile. Goal: Develop a biomarker-based predictive model that assists in early classification of INS subtypes.
4 secondary outcomes
Genetic and Epigenetic Risk Factors
Time frame: Up to 6 months from enrollment after initial diagnosis.
Immune System Alterations
Time frame: Up to 1 year from enrollment after initial diagnosis.
Proteomic Patterns in Serum and Urine
Time frame: Up to 1 year from enrollment after initial diagnosis.
Molecular Profile of Healthy Control Group
Time frame: At a single time point during enrollment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Individual participant dataSharing planned: No. The PRECISE study does not plan to share Individual Participant Data (IPD). This decision prioritizes the protection of participant confidentiality and aligns with the study's ethical guidelines, ensuring that sensitive genetic, transcriptomic, and proteomic information remains secure. As such, no IPD collected throughout the trial will be made available publicly or for secondary research purposes.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giovanni Montini, Doctor of Medicine principal investigator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Questions about this trial
What is this clinical trial studying?
An observational study of Nephrotic Syndrome Steroid-Dependent and Nephrotic Syndrome Steroid-Resistant, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Federica Lugani, Doctor of Medicine (+39 02 5503 3434, federica.lugani@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Predictive Molecular Signature of INS Progression (time frame: Up to 1 year from enrollment after initial diagnosis.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.