Clinical Trial: LYSO-PROVE - Determine the Prognostic Value of Lyso-Gb1 for Monitoring the Progress of Gaucher Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Lyso-Gb1 as Long-term Prognostic Biomarker in Gaucher Disease - an International Multicenter Epidemiological Study (LYSO-PROVE) to Determine the Prognostic Value of Lyso-Gb1 for Monitoring the Progres

Brief Summary: This study should 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

Detailed Summary:

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. Gaucher disease is the most common sphingolipidosis and it is among the most frequent inherited diseases among the ethnic group of Ashkenazi Jews. The gene that encodes for glucocerebrosidase is located on the long arm of the chromosome 1 and contains 11 exons. So far, more than 400 different mutations have been described in Gaucher patients, the most frequent of which is the missense mutation but also the frame-shift and splice-site mutation and insertions and deletions are known. The more frequent mutations are N370S, L444P, IVS2+1G>A, c.84insG, R463C, and R496H. Clinical symptoms are numerous. The classical symptoms affect visceral organs (hepatosplenomegaly) and the skeletal system (bone marrow infiltrations up to bone infarcts and pathological fractures) with consecutive changes in the blood panel (anemia, thrombocytopenia) (Sidransky, 2004).A major distinguishing factor is the occurrence of neurological manifestations (myoclonus epilepsy, hydrocephalus, eye motion disorders). Today, it is discussed whether the division into the classical three types of disease (type 1: non-neuronopathic form; type 2: the acute neuronopathic form; type 3: the chronic neuronopathic form) are still applicable because in clinical practice the presenting symptoms are only insufficiently reflected with this classification.

There is no clear genotype-phenotype relationship. The same DNA mutation is seen in patients with a completely different characterization of the disease. An exception is the mutation N370S, which so far has been found only in the visceral form (type1), but still may have a high phenotypic heterogeneity in GD Type 1 (Fairley et al., 2
Sponsor: University of Rostock

Current Primary Outcome: 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 [ Time Frame: 48 month ]

Original Primary Outcome: Same as current

Current Secondary Outcome: 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,Quality of life measured with the SF-36 [ Time Frame: 48 month ]

Original Secondary Outcome: Same as current

Information By: University of Rostock

Dates:
Date Received: March 13, 2015
Date Started: March 2015
Date Completion: May 2019
Last Updated: May 4, 2017
Last Verified: May 2017