Lysosomal Storage DiseasesLYSO-PROOFNCT02416661
Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease
An observational study of Lysosomal Storage Diseases and Gaucher Disease, run by CENTOGENE GmbH Rostock at 8 sites in 7 countries.
Trial summary
International, multicenter, epidemiological study to demonstrate the correlation and predictive value of lyso-Gb1 concentration with the clinical severity of naïve, initially non-ERT/SRT Gaucher disease type 1 and during the study ERT/SRT-newly started Gaucher type 1 patients and to correlate lyso-Gb1 concentration… Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Lysosomal Storage Diseases, Gaucher Disease, Sphingolipidoses
- How many people
- 299 participants
- Where
- 8 sitesin 7 countries
- Study dates
- 27 Aug 2018to 15 Jan 2021
- 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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Male or female patients aged 6 months or older with genetically confirmed diagnosis of Gaucher disease type 1 without treatment prior to enrollment or no treatment for more than 24 months ago
Who may be able to join
- Male or female patients aged 6 months or older
- Patients with genetically confirmed diagnosis of Gaucher disease type 1
- No prior treatment with enzyme replacement therapy or substrate reduction therapy ro no traetment for more than 24 months
- Signed informed consent by parents/legal guardian and patient
Who cannot join
- Male or female patients being younger than 6 months
- Patients without genetically confirmed diagnosis of Gaucher disease type 1
- Gaucher disease 2 or 3
- Patient is currently undergoing enzyme replacement therapy or substrate reduction therapy
- Missing signed informed consent
Trial locations and contacts
8 sites in 7 countries.
8 sites in 7 countries
Greece1 site
Aristotle University of Thessaloniki, Ippokration General Hospital
Thessaloniki, 54642
Pakistan1 site
The Children's Hospital and the Institute of Child Health
Lahore, Punjab Province, 54600
About this study
Official title: Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease: An International, Multicenter, Epidemiological Protocol
International, multicenter, epidemiological study to demonstrate the correlation and predictive value of lyso-Gb1 concentration with the clinical severity of naïve, initially non-ERT/SRT Gaucher disease type 1 and during the study ERT/SRT-newly started Gaucher type 1 patients and to correlate lyso-Gb1 concentration with the clinical improvement of ERT or SRT treated Gaucher type 1 and the clinical course of non-treated patients based on GD-DS3
Read the detailed description
Gaucher disease is an autosomal recessive inherited lysosomal storage disorder. The disease is caused by the hereditary deficiency of the glucocerebrosidase, a lysosomal enzyme that breaks down glucocerebroside into glucose and ceramide.
To date a definitive diagnosis of Gaucher's disease can only be made applying biochemical testing measuring the reduced enzymatic activity of the beta-glucosidase together with genetic confirmation. Since numerous different mutations may be the cause of a particular lysosomal storage disease the sequencing of the entire beta-glucosidase gene is applied in Gaucher's disease in order to confirm the genetic diagnosis.
The use of primary storage molecules as biomarker was assessed for glucosylceramide (Gb1) in plasma of Gaucher's disease patients and compared to the level of Gb1 in healthy individuals.
In order to establish a sensitive and specific biomarker for GD, we compared mass spectra of the plasma of healthy controls and GD patients using HPLC and tandem mass spectrometry. Mass spectra that differed most between patients and controls were analysed in more detail. The resulting biomarker, which was patented in June 2011 (PCT/EP2012/002409), was lyso - Gb1. We identified this compound as a reliable, sensitive and specific biomarker for GD in a cohort of GD patients. Furthermore, in a pilot study we evaluated whether lyso-Gb1 is related to the specific genotypes and is reliable for long-term monitoring of the efficiency of therapy.
The aim this study is therefore to investigate lyso-Gb1 as a long-term prognostic marker in naïve, non-ERT/SRT GD type 1 patients by monitoring over the course of 36 months.
- Keywords
- Gaucher Disease type 1, Lymphatic Diseases, Lipid Metabolism, Inborn Errors, Lipid Metabolism Disorders, Lipidoses
- Medical subject headings
- Lysosomal Storage Diseases, Gaucher Disease, Sphingolipidoses, Lymphatic Diseases, Lipid Metabolism, Inborn Errors, Lipid Metabolism Disorders, Lipidoses
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 |
|---|---|---|
| Participants diagnosed with Gaucher disease | Participants with genetically confirmed diagnosis of Gaucher disease type 1 older than 6 months old |
What is being measured
The primary outcome is the main question the study is designed to answer.
Demonstrating the correlation and predictive value of lyso-Gb1 concentration with the clinical severity of naïve, initially non-ERT/SRT Gaucher disease type 1 and during the study ERT/SRT-newly started Gaucher type 1 patients
lyso-Gb1 will be analzyed via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.
Measured: 48 month
Secondary outcomes (1)
Correlating lyso-Gb1 concentration with the clinical improvement of ERT or SRT treated Gaucher type 1 and the clinical course of non-treated patients based on GD-DS3.
lyso-Gb1 will be analysed over a period of 36 months via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) to demonstrate the course of the biomarker.
Measured: 48 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2015 (estimated)
- Study start27 Aug 2018
- Primary completion15 Jan 2021
- Study completion15 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lysosomal Storage DiseasesStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 299 participants (actual)
Sponsor and investigators
- Lead sponsor
- CENTOGENE GmbH Rostock
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter Bauer, M.D., Study chair, CENTOGENE GmbH Rostock
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02416661
- Sponsor's protocol ID
- LP 06-2018
- Acronym
- LYSO-PROOF
- Status last verified
- Apr 2020
- First submitted
- 13 Mar 2015
- Last updated
- 28 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Elstein D, Mellgard B, Dinh Q, Lan L, Qiu Y, Cozma C, Eichler S, Bottcher T, Zimran A. Reductions in glucosylsphingosine (lyso-Gb1) in treatment-naive and previously treated patients receiving velaglucerase alfa for type 1 Gaucher disease: Data from phase 3 clinical trials. Mol Genet Metab. 2017 Sep;122(1-2):113-120. doi: 10.1016/j.ymgme.2017.08.005. Epub 2017 Aug 24.
PubMed 28851512
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease: An International, Multicenter, Epidemiological Protocol
- ClinicalTrials.gov ID
- NCT02416661
- Acronym / sponsor ID
- LYSO-PROOF / LP 06-2018
- Keywords
- Gaucher Disease type 1, Lymphatic Diseases, Lipid Metabolism, Inborn Errors, Lipid Metabolism Disorders, Lipidoses
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 299 participants (actual)
- Lead sponsor
- CENTOGENE GmbH RostockIndustry (pharma, biotech, devices)
- Study start
- 27 Aug 2018 (actual)
- Primary completion
- 15 Jan 2021 (actual)
- Study completion
- 15 Jan 2021 (actual)
- First posted
- 15 Apr 2015 (estimated)
- 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.
International, multicenter, epidemiological study to demonstrate the correlation and predictive value of lyso-Gb1 concentration with the clinical severity of naïve, initially non-ERT/SRT Gaucher disease type 1 and during the study ERT/SRT-newly started Gaucher type 1 patients and to correlate lyso-Gb1 concentration with the clinical improvement of ERT or SRT treated Gaucher type 1 and the clinical course of non-treated patients based on GD-DS3
Detailed description
Gaucher disease is an autosomal recessive inherited lysosomal storage disorder. The disease is caused by the hereditary deficiency of the glucocerebrosidase, a lysosomal enzyme that breaks down glucocerebroside into glucose and ceramide.
To date a definitive diagnosis of Gaucher's disease can only be made applying biochemical testing measuring the reduced enzymatic activity of the beta-glucosidase together with genetic confirmation. Since numerous different mutations may be the cause of a particular lysosomal storage disease the sequencing of the entire beta-glucosidase gene is applied in Gaucher's disease in order to confirm the genetic diagnosis.
The use of primary storage molecules as biomarker was assessed for glucosylceramide (Gb1) in plasma of Gaucher's disease patients and compared to the level of Gb1 in healthy individuals.
In order to establish a sensitive and specific biomarker for GD, we compared mass spectra of the plasma of healthy controls and GD patients using HPLC and tandem mass spectrometry. Mass spectra that differed most between patients and controls were analysed in more detail. The resulting biomarker, which was patented in June 2011 (PCT/EP2012/002409), was lyso - Gb1. We identified this compound as a reliable, sensitive and specific biomarker for GD in a cohort of GD patients. Furthermore, in a pilot study we evaluated whether lyso-Gb1 is related to the specific genotypes and is reliable for long-term monitoring of the efficiency of therapy.
The aim this study is therefore to investigate lyso-Gb1 as a long-term prognostic marker in naïve, non-ERT/SRT GD type 1 patients by monitoring over the course of 36 months.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants diagnosed with Gaucher disease | – | –Participants with genetically confirmed diagnosis of Gaucher disease type 1 older than 6 months old |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Male or female patients aged 6 months or older with genetically confirmed diagnosis of Gaucher disease type 1 without treatment prior to enrollment or no treatment for more than 24 months ago
Key inclusion criteria (4 listed)
- Male or female patients aged 6 months or older
- Patients with genetically confirmed diagnosis of Gaucher disease type 1
- No prior treatment with enzyme replacement therapy or substrate reduction therapy ro no traetment for more than 24 months
- Signed informed consent by parents/legal guardian and patient
Key exclusion criteria (5 listed)
- Male or female patients being younger than 6 months
- Patients without genetically confirmed diagnosis of Gaucher disease type 1
- Gaucher disease 2 or 3
- Patient is currently undergoing enzyme replacement therapy or substrate reduction therapy
- Missing signed informed consent
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
Demonstrating the correlation and predictive value of lyso-Gb1 concentration with the clinical severity of naïve, initially non-ERT/SRT Gaucher disease type 1 and during the study ERT/SRT-newly started Gaucher type 1 patients
Time frame: 48 month
lyso-Gb1 will be analzyed via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.
1 secondary outcome
Correlating lyso-Gb1 concentration with the clinical improvement of ERT or SRT treated Gaucher type 1 and the clinical course of non-treated patients based on GD-DS3.
Time frame: 48 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2021.
- Derived from this study: PubMed 28851512Elstein D, Mellgard B, Dinh Q, Lan L, Qiu Y, Cozma C, Eichler S, Bottcher T, Zimran A. Reductions in glucosylsphingosine (lyso-Gb1) in treatment-naive and previously treated patients receiving velaglucerase alfa for type 1 Gaucher disease: Data from phase 3 clinical trials. Mol Genet Metab. 2017 Sep;122(1-2):113-120. doi: 10.1016/j.ymgme.2017.08.005. Epub 2017 Aug 24.
- CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for patientsLink provided by the sponsor.
- 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.
Peter Bauer, M.D. study chair
CENTOGENE GmbH Rostock
8 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lysosomal Storage Diseases and Gaucher Disease, run by CENTOGENE GmbH Rostock at 8 sites in 7 countries.
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 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: finished, as of the sponsor's last update on 28 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Morocco, Albania, Greece, India, Israel and 2 more countries. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Demonstrating the correlation and predictive value of lyso-Gb1 concentration with the clinical severity of naïve, initially non-ERT/SRT Gaucher disease type 1 and during the study ERT/SRT-newly started Gaucher type 1 patients (time frame: 48 month). 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 NCT02416661, which also lists 1 linked publication.
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 28 May 2021.