Nephrotic SyndromeNCT06325137
Transcriptome Analysis in Idiopathic Nephrotic Syndrome: Steroid Responsiveness
An observational study of Nephrotic Syndrome, run by IRCCS Burlo Garofolo at 1 site in Italy.
Trial summary
Idiopathic nephrotic syndrome (INS) affects the glomerular barrier by damaging the podocytes with foot process effacement, leading to a pathological increase of permeability and protein loss. INS classification is based on the clinical response to glucocorticoid (GC) therapy. Read more about this study
- Who is it for?
- Ages 1 year to 12 years
- Conditions the study is for
- Nephrotic Syndrome
- What is being tested?
- Transcriptome analyses
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- 16 Mar 2023to Mar 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 1 year to 12 years
- All sexes
- No healthy volunteers
- Child
Study population: Children with nephrosic syndrome
Who may be able to join
- clinical diagnosis of INS
- age 1 - 12 years
- signed informed consent by parents or legal guardians
- For controls: aged-matched individuals with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
Who cannot join
- Patients aged <1 year or > 12 years
- Patients diagnosed with a secondary or genetic form of NS
- For controls: the presence of coexisting chronic kidney failure, autoimmune or autoinflammatory disease, or endocrinologic disorders.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"
Trieste, 34137
Marco Pennesi, MD, +39.040-3785263, marco.pennesi@burlo.trieste.it
Barbara Bonifacio, +39.040.3785.422, barbara.bonifacio@burlo.trieste.it
About this study
Official title: Transcriptome Analysis in Idiopathic Nephrotic Syndrome: an Insight Into the Mechanisms of Steroid Responsiveness
Idiopathic nephrotic syndrome (INS) affects the glomerular barrier by damaging the podocytes with foot process effacement, leading to a pathological increase of permeability and protein loss. INS classification is based on the clinical response to glucocorticoid (GC) therapy. When GCs treatment fails to induce remission in a four-six weeks course, patients are defined as affected with steroid-resistant nephrotic syndrome (SRNS).
The whole transcriptome sequencing could consent the INS classification at onset, prior to glucocorticoids (GCs) treatment, allowing to reduction of unuseful GCs treatment. RNA sequencing technologies allow an extensive characterization of the transcriptomic profile and permit global changes in gene expression levels between different conditions such as active and remission of the disease.
Read more
Of great interest is the research of a molecular biomarker to predict steroid resistance, a predictor that is not yet available. Among the candidate biomarkers, pharmacogenomic determinants are promising, even if available studies are still limited. Among these, some epigenetic factors have been previously suggested. Data obtained in animal models suggests that nucleotide-binding oligomerization domain-like receptors (NOD-like receptor) pyrin domain containing 3 (NLRP3) inflammasome can be deregulated in a wide variety of glomerular diseases, including those causing INS. Another potential marker involved in steroid response is the long noncoding RNA GAS5. Data reported in the literature indicate that abnormal levels of GAS5 in peripheral blood mononuclear cells (PBMCs) may alter steroid effectiveness in autoimmune diseases, such as inflammatory bowel disease.
Preliminary findings show that the study of NLRP3 promoter methylation could be reduced in the blood of SRNS compared with steroid-sensitive nephrotic syndrome (SSNS) patients. Moreover, unpublished encouraging results on the association between Growth Arrest Specific 5 (GAS5) expression and steroid response in INS in PBMCs were obtained in a preliminary study conducted on 8 patients with the first episode of INS. PBMCs were obtained and GAS5 gene expression was evaluated using TaqMan technology. Patients affected with SRNS presented significantly higher levels of GAS5 in comparison with the SSNS group. In PBMCs from SRNS patients, the GAS5 expression could reduce the availability for binding to GCs target genes of the activated GCs receptor and suppresses GC transcriptional activity.
- Conditions
- Nephrotic Syndrome
- Being tested
- Transcriptome analyses
- Keywords
- Whole transcriptome sequencing, Idiopathic nephrotic syndrome pathogenesis, Steroid responsiveness prediction
- Medical subject headings
- Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcriptome analysesDiagnostic test
A sample of peripheral whole blood cells will be collected at the onset before the initiation of steroid treatment (time 0, t0) and after 6 weeks at the definition of steroid sensitivity/unresponsiveness (time 1, t1).
| Study group | Role | What they receive |
|---|---|---|
| Patients with steroid-resistant nephrotic syndrome | Identification of a possible molecular signatures at t0 by whole transcriptome analysis from PBMCs Receives: Diagnostic Test: Transcriptome analyses | |
| Patients with steroid sensitive nephrotic syndrome | Identification of a possible molecular signatures at t0 by whole transcriptome analysis from PBMCs Receives: Diagnostic Test: Transcriptome analyses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Between groups differences in molecular signature by whole transcriptome analysis
A sample of peripheral whole blood cells will be collected at the onset before the initiation of steroid treatment (time 0, t0)
Measured: At enrolment (T0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2024
- Study start16 Mar 2023
- Primary completionMar 2025 (estimated)
- Study completionMar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nephrotic SyndromeStudies of the same condition, open and under way.
- 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
- Cross-sectional
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Burlo Garofolo
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06325137
- Sponsor's protocol ID
- RC 24/2022
- Status last verified
- Mar 2024
- First submitted
- 15 Mar 2024
- Last updated
- 22 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcriptome Analysis in Idiopathic Nephrotic Syndrome: an Insight Into the Mechanisms of Steroid Responsiveness
- ClinicalTrials.gov ID
- NCT06325137
- Acronym / sponsor ID
- RC 24/2022
- Conditions
- Nephrotic Syndrome
- Keywords
- Whole transcriptome sequencing, Idiopathic nephrotic syndrome pathogenesis, Steroid responsiveness prediction
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- IRCCS Burlo GarofoloUniversity, hospital or other
- Study start
- 16 Mar 2023 (actual)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Mar 2025 (estimated)
- First posted
- 22 Mar 2024 (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 (INS) affects the glomerular barrier by damaging the podocytes with foot process effacement, leading to a pathological increase of permeability and protein loss. INS classification is based on the clinical response to glucocorticoid (GC) therapy. When GCs treatment fails to induce remission in a four-six weeks course, patients are defined as affected with steroid-resistant nephrotic syndrome (SRNS).
The whole transcriptome sequencing could consent the INS classification at onset, prior to glucocorticoids (GCs) treatment, allowing to reduction of unuseful GCs treatment. RNA sequencing technologies allow an extensive characterization of the transcriptomic profile and permit global changes in gene expression levels between different conditions such as active and remission of the disease.
Of great interest is the research of a molecular biomarker to predict steroid resistance, a predictor that is not yet available. Among the candidate biomarkers, pharmacogenomic determinants are promising, even if available studies are still limited. Among these, some epigenetic factors have been previously suggested. Data obtained in animal models suggests that nucleotide-binding oligomerization domain-like receptors (NOD-like receptor) pyrin domain containing 3 (NLRP3) inflammasome can be deregulated in a wide variety of glomerular diseases, including those causing INS. Another potential marker involved in steroid response is the long noncoding RNA GAS5. Data reported in the literature indicate that abnormal levels of GAS5 in peripheral blood mononuclear cells (PBMCs) may alter steroid effectiveness in autoimmune diseases, such as inflammatory bowel disease.
Preliminary findings show that the study of NLRP3 promoter methylation could be reduced in the blood of SRNS compared with steroid-sensitive nephrotic syndrome (SSNS) patients. Moreover, unpublished encouraging results on the association between Growth Arrest Specific 5 (GAS5) expression and steroid response in INS in PBMCs were obtained in a preliminary study conducted on 8 patients with the first episode of INS. PBMCs were obtained and GAS5 gene expression was evaluated using TaqMan technology. Patients affected with SRNS presented significantly higher levels of GAS5 in comparison with the SSNS group. In PBMCs from SRNS patients, the GAS5 expression could reduce the availability for binding to GCs target genes of the activated GCs receptor and suppresses GC transcriptional activity.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with steroid-resistant nephrotic syndrome | – | Diagnostic Test: Transcriptome analysesIdentification of a possible molecular signatures at t0 by whole transcriptome analysis from PBMCs |
| Patients with steroid sensitive nephrotic syndrome | – | Diagnostic Test: Transcriptome analysesIdentification of a possible molecular signatures at t0 by whole transcriptome analysis from PBMCs |
Who may qualify
- Ages
- 1 year to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Children with nephrosic syndrome
Key inclusion criteria (4 listed)
- clinical diagnosis of INS
- age 1 - 12 years
- signed informed consent by parents or legal guardians
- For controls: aged-matched individuals with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
Key exclusion criteria (3 listed)
- Patients aged <1 year or > 12 years
- Patients diagnosed with a secondary or genetic form of NS
- For controls: the presence of coexisting chronic kidney failure, autoimmune or autoinflammatory disease, or endocrinologic disorders.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcriptome analysesA sample of peripheral whole blood cells will be collected at the onset before the initiation of steroid treatment (time 0, t0) and after 6 weeks at the definition of steroid sensitivity/unresponsiveness (time 1, t1). | Diagnostic test | Patients with steroid sensitive nephrotic syndrome, Patients with steroid-resistant nephrotic syndrome |
Primary outcome
Between groups differences in molecular signature by whole transcriptome analysis
Time frame: At enrolment (T0)
A sample of peripheral whole blood cells will be collected at the onset before the initiation of steroid treatment (time 0, t0)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Nephrotic Syndrome, run by IRCCS Burlo Garofolo at 1 site in Italy.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marco Pennesi, MD (+39. 040-3785263, marco.pennesi@burlo.trieste.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Between groups differences in molecular signature by whole transcriptome analysis (time frame: At enrolment (T0)). 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 22 Mar 2024.