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CompletedNCT02416661LYSO-PROOFUpdated May 28, 2021

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

An observational study in Lysosomal Storage Diseases, Gaucher Disease and Sphingolipidoses, sponsored by CENTOGENE GmbH Rostock. Completed at 8 sites in 7 countries. Open to participants aged 6 Months and older. Per ClinicalTrials.gov, last updated 2021-05-28.

Sponsored by CENTOGENE GmbH Rostock · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
299
Ages
6 Months and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • Lysosomal Storage Diseases
  • Gaucher Disease
  • Sphingolipidoses

Keywords

  • Gaucher Disease type 1
  • Lymphatic Diseases
  • Lipid Metabolism, Inborn Errors
  • Lipid Metabolism Disorders
  • Lipidoses
03

Who can participate

Ages eligible
6 Months and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Probability sample

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

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

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
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
299 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • Participants diagnosed with Gaucher disease

    Participants with genetically confirmed diagnosis of Gaucher disease type 1 older than 6 months old

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 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.

    Time frame: 48 month

06

Study locations

8 sites
  • University Hospital Center Mother Teresa
    Tirana, 10001, Albania
  • Aristotle University of Thessaloniki, Ippokration General Hospital
    Thessaloniki, 54642, Greece
  • Centre for Human Genetics
    Bangalore, 560100, India
  • Shaare Zedek Medical Center
    Jerusalem, 9103 102, Israel
  • Children hospital
    Rabat, 10100, Morocco
  • Hopital d'Enfant
    Rabat, 10100, Morocco
  • The Children's Hospital and the Institute of Child Health
    Lahore, Punjab 54600, Pakistan
  • Hospital Universitari de Bellvitge (planta 7.1)
    Barcelona, 08907, Spain
07

References and documents

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 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT02416661
Lead sponsor
CENTOGENE GmbH Rostock
Responsible party
Sponsor
First posted
Apr 15, 2015
Start date
Aug 27, 2018
Primary completion
Jan 15, 2021
Completion
Jan 15, 2021
Last update
May 28, 2021

Study contacts

Peter Bauer, M.D.
study chair · CENTOGENE GmbH Rostock

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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