Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease

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

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Key information

Conditions

Lysosomal Storage Diseases Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Gaucher Disease Genetic Diseases, Inborn Hemic and Lymphatic Diseases Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Lymphatic Diseases Lysosomal Storage Diseases, Nervous System Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Sphingolipidoses

Age range

6 month and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University Hospital Center Mother Teresa, Tirana, Albania

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Primary outcomes

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.

Secondary outcomes

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

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.

Sponsors and collaborators

Lead sponsor

CENTOGENE GmbH Rostock

Industry

Registry information

Official study title

Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease: An International, Multicenter, Epidemiological Protocol

Acronym: LYSO-PROOF

Important dates

Study start: 2018
Primary completion: 2021
Study completion: 2021
First posted: Apr 15, 2015
Registry last updated: May 28, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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