Lysosomal Storage DiseasesLYSO-NEXTNCT07863479
NGS-Based Genetic Approach to Identify Rare Lysosomal Storage Disorders in Patients With Neurological Manifestations
A study testing NGS-based genetic testing in people with Lysosomal Storage Diseases, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial summary
LYSO-NEXT uses genetic sequencing to identify undiagnosed lysosomal storage disorders in adults with unexplained neurological symptoms. Participants undergo whole-exome sequencing, which examines the protein-coding regions of DNA. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lysosomal Storage Diseases
- What is being tested?
- NGS-based genetic testing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- 1 siteItaly
- Study dates
- 1 May 2024to Dec 2027
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent for participation in the study.
- Age 18 years or older.
- Neurological manifestations without an established genetic diagnosis: early-onset parkinsonism, ataxia, motor neuropathy, myopathy, intellectual disability, epilepsy, young-onset stroke, or chronic pain syndromes with childhood onset.
Who cannot join
- Neurological signs and symptoms definitively attributable to acquired causes, including trauma, tumors, infections, or acquired metabolic conditions.
Trial locations and contacts
1 site in 1 country.
Italy1 site
S.C. Neurologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
About this study
Official title: LYSO-NEXT: NGS-Based Genetic Approach to Identify Rare Lysosomal Storage Disorders in Patients With Neurological Manifestations
LYSO-NEXT uses genetic sequencing to identify undiagnosed lysosomal storage disorders in adults with unexplained neurological symptoms. Participants undergo whole-exome sequencing, which examines the protein-coding regions of DNA. A small subgroup with inconclusive results and strong clinical suspicion undergoes additional long-read sequencing to detect genetic changes that may be missed by the initial test. The study assesses the proportion of participants diagnosed with a lysosomal storage disorder and the diagnostic yield of each sequencing approach.
Read the detailed description
Participants undergo clinical assessment, pre-test genetic counseling, and a single blood collection for DNA extraction. Whole-exome sequencing data are initially analyzed using a virtual panel of lysosomal storage disorder genes; if no diagnosis is established, analysis is extended to other genes. Identified variants are confirmed by Sanger sequencing.
Approximately 10 selected participants undergo long-read sequencing to investigate structural variants. Selection focuses on unresolved cases with a single pathogenic variant in a gene associated with an autosomal recessive disorder or a strongly suggestive phenotype despite negative first-line testing.
Genetic findings guide clinical reassessment to evaluate genotype-phenotype compatibility. Participants who choose to receive their results are offered a genetic report and post-test counseling.
- Conditions
- Lysosomal Storage Diseases
- Being tested
- NGS-based genetic testing
- Keywords
- Next-Generation Sequencing, Whole-Exome Sequencing, Long-Read Sequencing
- Medical subject headings
- Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NGS-based genetic testingDiagnostic test
A single peripheral venous blood collection (two 7 mL EDTA tubes) is used for DNA extraction and whole-exome sequencing in all participants. First-line analysis uses the Nextera Exome Library protocol and Illumina NextSeq500 platform, followed by bioinformatic analysis for causal variants. Approximately 10 selected participants with unresolved findings and strong suspicion of a lysosomal storage disorder undergo second-line long-read sequencing without an additional blood collection. Testing is preceded by genetic counseling and followed by clinical reassessment and, for participants who choose to receive results, a genetic report and post-test counseling. The genetic analysis phase is expected to last approximately six months.
| Study group | Role | What they receive |
|---|---|---|
| NGS-based genetic diagnosis | Experimental | Adults with neurological manifestations and no established genetic diagnosis undergo pre-test counseling, a single venous blood collection, and first-line whole-exome sequencing. Approximately 10 selected participants undergo additional long-read sequencing using the same sample. Genetic findings are followed by clinical reassessment and, for participants who choose to receive results, a genetic report and post-test counseling. Receives: Diagnostic Test: NGS-based genetic testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of genetically diagnosed lysosomal storage disorders
Proportion of enrolled participants with a genetically diagnosed lysosomal storage disorder, calculated as the number of participants diagnosed with a lysosomal storage disorder divided by the total number of participants recruited. Genetic findings are assessed together with clinical reassessment to establish genotype-phenotype compatibility.
Measured: At completion of genetic analysis and clinical reassessment, approximately 6 months after blood sampling
Secondary outcomes (2)
Diagnostic yield of whole-exome sequencing
Proportion of participants receiving a genetic diagnosis through whole-exome sequencing (WES), calculated as the number of cases diagnosed by WES divided by the number of cases sequenced using WES.
Measured: At completion of whole-exome sequencing analysis and clinical reassessment, approximately 6 months after blood sampling
Diagnostic yield of long-read next-generation sequencing
Proportion of selected participants receiving a genetic diagnosis through long-read next-generation sequencing, calculated as the number of cases diagnosed by long-read sequencing divided by the number of cases sequenced using this approach. This analysis is performed in approximately 10 highly selected participants whose first-line short-read analysis has not established a complete diagnosis.
Measured: At completion of long-read sequencing analysis and clinical reassessment, expected approximately 6 months after blood sampling
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2026
- Study start1 May 2024
- Primary completion30 Sep 2026
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lysosomal Storage DiseasesStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants undergo first-line whole-exome sequencing. Approximately 10 selected participants undergo additional long-read sequencing based on first-line findings and clinical suspicion.
- Masking
- None (open label)
- Enrolment
- 1,000 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07863479
- Sponsor's protocol ID
- SGZ202213851
- Other IDs
- PR-0536
- Acronym
- LYSO-NEXT
- Status last verified
- Oct 2026
- First submitted
- 2 Oct 2026
- Last updated
- 7 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Marx V. Method of the year: long-read sequencing. Nat Methods. 2023 Jan;20(1):6-11. doi: 10.1038/s41592-022-01730-w. No abstract available.
PubMed 36635542Buermans HP, den Dunnen JT. Next generation sequencing technology: Advances and applications. Biochim Biophys Acta. 2014 Oct;1842(10):1932-1941. doi: 10.1016/j.bbadis.2014.06.015. Epub 2014 Jul 1.
PubMed 24995601Vellodi A. Lysosomal storage disorders. Br J Haematol. 2005 Feb;128(4):413-31. doi: 10.1111/j.1365-2141.2004.05293.x.
PubMed 15686451
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LYSO-NEXT: NGS-Based Genetic Approach to Identify Rare Lysosomal Storage Disorders in Patients With Neurological Manifestations
- ClinicalTrials.gov ID
- NCT07863479
- Acronym / sponsor ID
- LYSO-NEXT / SGZ202213851
- Conditions
- Lysosomal Storage Diseases
- Keywords
- Next-Generation Sequencing, Whole-Exome Sequencing, Long-Read Sequencing
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,000 participants (actual)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- 1 May 2024 (actual)
- Primary completion
- 30 Sep 2026 (actual)
- Study completion
- Dec 2027 (estimated)
- First posted
- 7 Oct 2026 (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.
LYSO-NEXT uses genetic sequencing to identify undiagnosed lysosomal storage disorders in adults with unexplained neurological symptoms. Participants undergo whole-exome sequencing, which examines the protein-coding regions of DNA. A small subgroup with inconclusive results and strong clinical suspicion undergoes additional long-read sequencing to detect genetic changes that may be missed by the initial test. The study assesses the proportion of participants diagnosed with a lysosomal storage disorder and the diagnostic yield of each sequencing approach.
Detailed description
Participants undergo clinical assessment, pre-test genetic counseling, and a single blood collection for DNA extraction. Whole-exome sequencing data are initially analyzed using a virtual panel of lysosomal storage disorder genes; if no diagnosis is established, analysis is extended to other genes. Identified variants are confirmed by Sanger sequencing.
Approximately 10 selected participants undergo long-read sequencing to investigate structural variants. Selection focuses on unresolved cases with a single pathogenic variant in a gene associated with an autosomal recessive disorder or a strongly suggestive phenotype despite negative first-line testing.
Genetic findings guide clinical reassessment to evaluate genotype-phenotype compatibility. Participants who choose to receive their results are offered a genetic report and post-test counseling.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants undergo first-line whole-exome sequencing. Approximately 10 selected participants undergo additional long-read sequencing based on first-line findings and clinical suspicion.
| Arm | Type | Receives |
|---|---|---|
| NGS-based genetic diagnosis | Experimental | Diagnostic Test: NGS-based genetic testingAdults with neurological manifestations and no established genetic diagnosis undergo pre-test counseling, a single venous blood collection, and first-line whole-exome sequencing. Approximately 10 selected participants undergo additional long-read sequencing using the same sample. Genetic findings are followed by clinical reassessment and, for participants who choose to receive results, a genetic report and post-test counseling. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Signed informed consent for participation in the study.
- Age 18 years or older.
- Neurological manifestations without an established genetic diagnosis: early-onset parkinsonism, ataxia, motor neuropathy, myopathy, intellectual disability, epilepsy, young-onset stroke, or chronic pain syndromes with childhood onset.
Key exclusion criteria (1 listed)
- Neurological signs and symptoms definitively attributable to acquired causes, including trauma, tumors, infections, or acquired metabolic conditions.
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 |
|---|---|---|
| NGS-based genetic testingA single peripheral venous blood collection (two 7 mL EDTA tubes) is used for DNA extraction and whole-exome sequencing in all participants. First-line analysis uses the Nextera Exome Library protocol and Illumina NextSeq500 platform, followed by bioinformatic analysis for causal variants. Approximately 10 selected participants with unresolved findings and strong suspicion of a lysosomal storage disorder undergo second-line long-read sequencing without an additional blood collection. Testing is preceded by genetic counseling and followed by clinical reassessment and, for participants who choose to receive results, a genetic report and post-test counseling. The genetic analysis phase is expected to last approximately six months. | Diagnostic test | NGS-based genetic diagnosis |
Primary outcome
Prevalence of genetically diagnosed lysosomal storage disorders
Time frame: At completion of genetic analysis and clinical reassessment, approximately 6 months after blood sampling
Proportion of enrolled participants with a genetically diagnosed lysosomal storage disorder, calculated as the number of participants diagnosed with a lysosomal storage disorder divided by the total number of participants recruited. Genetic findings are assessed together with clinical reassessment to establish genotype-phenotype compatibility.
2 secondary outcomes
Diagnostic yield of whole-exome sequencing
Time frame: At completion of whole-exome sequencing analysis and clinical reassessment, approximately 6 months after blood sampling
Diagnostic yield of long-read next-generation sequencing
Time frame: At completion of long-read sequencing analysis and clinical reassessment, expected approximately 6 months after blood sampling
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 7 Oct 2026.
- Background: PubMed 36635542Marx V. Method of the year: long-read sequencing. Nat Methods. 2023 Jan;20(1):6-11. doi: 10.1038/s41592-022-01730-w. No abstract available.
- Background: PubMed 24995601Buermans HP, den Dunnen JT. Next generation sequencing technology: Advances and applications. Biochim Biophys Acta. 2014 Oct;1842(10):1932-1941. doi: 10.1016/j.bbadis.2014.06.015. Epub 2014 Jul 1.
- Background: PubMed 15686451Vellodi A. Lysosomal storage disorders. Br J Haematol. 2005 Feb;128(4):413-31. doi: 10.1111/j.1365-2141.2004.05293.x.
- Individual participant dataSharing planned: Undecided
Related trials for Lysosomal Storage Diseases
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
RecruitingObservational study
Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders
Neurological Regression, Myoclonus
RecruitingObservational study
Parkinson's Disease in Type 1 Gaucher Disease
Parkinson Disease (PD), Type 1 Gaucher Disease
RecruitingObservational study
Oxidative Stress and Inflammatory Biomarkers in Gaucher Disease
Gaucher Disease Type I, Oxidative Stress
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NGS-based genetic testing in people with Lysosomal Storage Diseases, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico 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 3 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 7 Oct 2026. 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?
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?
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?
Prevalence of genetically diagnosed lysosomal storage disorders (time frame: At completion of genetic analysis and clinical reassessment, approximately 6 months after blood sampling). 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 NCT07863479, which also lists 3 linked publications.
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 7 Oct 2026.