Chronic Kidney DiseasesNCT06325072

Set-up of a Platform for Personalized Diagnosis of Rare Kidney Diseases (NIKE)

A study testing Conclusive genetic testing, Genotype-phenotype correlation for personalized diagnosis and Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chip in people with Chronic Kidney Diseases, run by Meyer Children's Hospital IRCCS at 4 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

Who is it for?: Ages Up to 40 years
Conditions the study is for: Chronic Kidney Diseases
What is being tested?: Conclusive genetic testing, Genotype-phenotype correlation for personalized diagnosis and Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chip
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 160 participants
Where: 4 sitesItaly
Study dates: 9 Jul 2021to 30 Jun 2024
Phase: Interventional
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 Up to 40 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

family history of kidney disease and/or parental consanguinity;
extra-renal involvement (e.g., sensorineural hearing loss);
resistance to treatment (e.g., immunosuppressive);
metabolic acidosis or metabolic alkalosis in the absence of renal failure;
ultrasound detection of of at least 2 cystic lesions in each kidney or nephrocalcinosis;
ultrasound detection of congenital abnormalities of the kidney and urinary tract (CAKUT) and CKD stage ≥ 2 according to KDIGO definition
informed consent form.

Who cannot join

age > 40
refuse to participate to the study

Trial locations and contacts

4 sites in 1 country.

Italy4 sites

Azienda Ospedaliero Universitaria Careggi
Florence
Meyer Children's Hospital IRCCS
Florence
USL Toscana Centro
Florence
Azienda Ospedaliero Universitaria Pisana
Pisa

Other trials in Italy

About this study

Chronic kidney disease (CKD) is a major health problem, with steadily increasing incidence and prevalence and the threat of a true "epidemic". Converging evidence suggests a high prevalence of genetic etiology in rare kidney diseases and the list of new disease-causing genes is constantly updated. Recent advances in next-generation sequencing (NGS) technologies have prompted a significant improvement in the diagnosis of rare kidney diseases. Notwithstanding this, NGS generates high numbers of information that need to be properly analysed by the joint efforts of geneticists, nephrologists and bioinformatics in order to integrate clinical and genetic information in a personalized manner. In addition, in selected cases, the contribution of researchers proves essential for the development of experimental models of the disease to study and understand the pathogenic features and propose a personalized therapeutic approach. Such an innovative, integrated diagnostic paradigm is currently available in few centers all over the world and cannot be easily translated in daily clinical practice.

The aim of the study is to set-up an integrated diagnostic algorithm to extend the newest personalized diagnostic and treatment strategies for rare kidney diseases to all patients in the Tuscany region, under 40 years of age with kidney disease. This algorithm will be based on a constant cross-talk between participating centers and a dedicated multidisciplinary team. Diagnostic and therapeutic performances will be validated at European level.

Conditions: Chronic Kidney Diseases
Being tested: Conclusive genetic testing, Genotype-phenotype correlation for personalized diagnosis, Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chip
Medical subject headings: Renal Insufficiency, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Conclusive genetic testingDiagnostic test
Patients will be referred for genetic counseling at the study coordinating center. This will lead to a conclusive genetic diagnosis.
Genotype-phenotype correlation for personalized diagnosisDiagnostic test
Patients and their family members will undergo a thorough clinical reassessment at the study coordinating center to identify diagnostic handles of the suspected disease based on the genetic test result (reverse phenotyping). The clinical reassessment could include the performance of additional clinical and instrumental tests, as well as other specialized consultations. This will lead to a conclusive genetic diagnosis in a substantial proportion of cases, cases, who will then be provided with genetic counselling.
Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chipDiagnostic test
The investigators will perform functional assessment trough urine derived Renal Progenitor Cells (u-RPC) to establish the role of variants in determining the clinical phenotype.

Study groups in NCT06325072
Study group	Role	What they receive
Pathogenic variants	Experimental	Variants fitting bioinformatic prioritization criteria for pathogenicity according to ACMG guidelines and the clinical phenotype, and variants already reported in the literature will be defined as pathogenic variants Receives: Diagnostic Test: Conclusive genetic testing
Potentially Pathogenic Variants	Experimental	Variants fitting bioinformatic prioritization criteria but apparently do not correlate with the clinical phenotype and have not been previously reported in the literature will be defined as potentially pathogenic variants Receives: Diagnostic Test: Genotype-phenotype correlation for personalized diagnosis
Variants of Unknown Significance (VUS)	Experimental	Variants fitting the phenotype but not fitting bioinformatic prioritization criteria will be defined as variants of uncertain clinical significance (VUS) Receives: Diagnostic Test: Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chip

What is being measured

The primary outcome is the main question the study is designed to answer.

Validation of genetic diagnosis
The investigators will assess the role of potentially pathogenic variants and variants of uncertain clinical significance (VUS) in determining a conclusive genetic diagnosis by patient reassessment (reverse phenotyping) or in vitro functional studies.
In detail, after the results of ES, a multidisciplinary team will evaluate the results of sequencing and will eventually request additional investigations (e.g., laboratory or imaging tests, specific consultations, etc) to the patient and/or family member in order to look for previously undetected/overlooked signs of the genetic diseases suggested by ES (reverse phenotyping).
In vitro functional studies on u-RPC will be requested in a subset of patients. The number of patients with a conclusive diagnosis obtained trough these strategies will contribute to the overall diagnostic rate of the workflow (number of conclusive genetic diagnosis/number of patients enrolled in the study).
Measured: From enrollment (genetic testing) until the date of returning of genetic testing results (up to 6 months)

Secondary outcomes (2)

Identification of molecular pathways
The investigators aim to o identify molecular pathways that could represent potential therapeutic targets in a selection of patients carrying potentially pathogenic variants.
To this goal, the investigators will perform single-cell RNA sequencing on kidney biopsy fragments of patients who have undergone a diagnostic kidney biopsy. After obtaining intracellular transcriptome of individual cells carrying the potentially pathogenic variants, the investigators will compare their RNA expression profile to the same type of cells obtained from non-mutated patients.
Measured: From enrollment (genetic testing) until the last patient last visit, estimated up to 12 months
Explore the applicability of gene editing in rare kidney diseases
The investigators will explore the applicability of CRISPR/Cas9 gene editing in rare kidney diseases through u-RPCs obtained from patients carrying pathogenic mutations.
In order to achieve the rescue of disease causative variants, the investigators will perform a stable correction of genetic variants identified through CRISPR/Cas9 gene editing approach, in u-RPC isolated from patients carrying pathogenic variants.
Measured: From enrollment (genetic testing) until the last patient last visit, estimated up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Jul 202130 Jun 2024

First posted22 Mar 2024
Study start9 Jul 2021
Primary completion27 Jun 2023
Study completion30 Jun 2024 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Chronic Kidney DiseasesStudies of the same condition, open and under way.
More trials run by Meyer Children's Hospital IRCCSThe 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: Interventional
Phase: Phase N/A
Primary purpose: Diagnosis
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: Patients selected based on the inclusion criteria will be evaluated by a multidisciplinary team of experts. All the selected patients will undergo genetic testing by clinical exome sequencing and in silico filtering for a panel of genes described as causing or in association with CKD. Identified variants will be classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Reverse phenotyping will be performed according to the results of genetic testing. The results of the diagnostic work-up will be evaluated by a multi-disciplinary team of experts in order to establish conclusive diagnosis.
Masking: None (open label)
Enrolment: 160 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06325072
Sponsor's protocol ID: NIKE
Status last verified: Mar 2024
First submitted: 29 Feb 2024
Last updated: 22 Mar 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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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: Set-up of a Platform for Personalized Diagnosis of Rare Kidney Diseases (NIKE)
ClinicalTrials.gov ID: NCT06325072
Acronym / sponsor ID: NIKE
Conditions: Chronic Kidney Diseases
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 160 participants (estimated)
Lead sponsor: Meyer Children's Hospital IRCCSUniversity, hospital or other
Study start: 9 Jul 2021 (actual)
Primary completion: 27 Jun 2023 (actual)
Study completion: 30 Jun 2024 (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.

Study design

Primary purpose: Diagnosis
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: Patients selected based on the inclusion criteria will be evaluated by a multidisciplinary team of experts. All the selected patients will undergo genetic testing by clinical exome sequencing and in silico filtering for a panel of genes described as causing or in association with CKD. Identified variants will be classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Reverse phenotyping will be performed according to the results of genetic testing. The results of the diagnostic work-up will be evaluated by a multi-disciplinary team of experts in order to establish conclusive diagnosis.

Arm	Type	Receives
Pathogenic variants	Experimental	Diagnostic Test: Conclusive genetic testingVariants fitting bioinformatic prioritization criteria for pathogenicity according to ACMG guidelines and the clinical phenotype, and variants already reported in the literature will be defined as pathogenic variants
Potentially Pathogenic Variants	Experimental	Diagnostic Test: Genotype-phenotype correlation for personalized diagnosisVariants fitting bioinformatic prioritization criteria but apparently do not correlate with the clinical phenotype and have not been previously reported in the literature will be defined as potentially pathogenic variants
Variants of Unknown Significance (VUS)	Experimental	Diagnostic Test: Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chipVariants fitting the phenotype but not fitting bioinformatic prioritization criteria will be defined as variants of uncertain clinical significance (VUS)

Who may qualify

Ages: Up to 40 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (7 listed)

family history of kidney disease and/or parental consanguinity;
extra-renal involvement (e.g., sensorineural hearing loss);
resistance to treatment (e.g., immunosuppressive);
metabolic acidosis or metabolic alkalosis in the absence of renal failure;
ultrasound detection of of at least 2 cystic lesions in each kidney or nephrocalcinosis;

Key exclusion criteria (2 listed)

age > 40
refuse to participate to the study

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
Conclusive genetic testingPatients will be referred for genetic counseling at the study coordinating center. This will lead to a conclusive genetic diagnosis.	Diagnostic test	Pathogenic variants
Genotype-phenotype correlation for personalized diagnosisPatients and their family members will undergo a thorough clinical reassessment at the study coordinating center to identify diagnostic handles of the suspected disease based on the genetic test result (reverse phenotyping). The clinical reassessment could include the performance of additional clinical and instrumental tests, as well as other specialized consultations. This will lead to a conclusive genetic diagnosis in a substantial proportion of cases, cases, who will then be provided with genetic counselling.	Diagnostic test	Potentially Pathogenic Variants
Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chipThe investigators will perform functional assessment trough urine derived Renal Progenitor Cells (u-RPC) to establish the role of variants in determining the clinical phenotype.	Diagnostic test	Variants of Unknown Significance (VUS)

Primary outcome

Validation of genetic diagnosis
Time frame: From enrollment (genetic testing) until the date of returning of genetic testing results (up to 6 months)
The investigators will assess the role of potentially pathogenic variants and variants of uncertain clinical significance (VUS) in determining a conclusive genetic diagnosis by patient reassessment (reverse phenotyping) or in vitro functional studies. In detail, after the results of ES, a multidisciplinary team will evaluate the results of sequencing and will eventually request additional investigations (e.g., laboratory or imaging tests, specific consultations, etc) to the patient and/or family member in order to look for previously undetected/overlooked signs of the genetic diseases suggested by ES (reverse phenotyping). In vitro functional studies on u-RPC will be requested in a subset of patients. The number of patients with a conclusive diagnosis obtained trough these strategies will contribute to the overall diagnostic rate of the workflow (number of conclusive genetic diagnosis/number of patients enrolled in the study).

2 secondary outcomes

Identification of molecular pathways
Time frame: From enrollment (genetic testing) until the last patient last visit, estimated up to 12 months
Explore the applicability of gene editing in rare kidney diseases
Time frame: From enrollment (genetic testing) until the last patient last visit, estimated up to 12 months

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: No

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End Stage Renal Disease
RecruitingPhase 3
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Berger Disease, Bergers Disease
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
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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.

The record lists no contact. Use the official record to reach the sponsor.

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 7 inclusion and 2 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 4 sites 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Validation of genetic diagnosis (time frame: From enrollment (genetic testing) until the date of returning of genetic testing results (up to 6 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06325072.

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.