Gaucher disease
Conditions
Interventions
Trade Name: DEFLEGMIN 75mg, kapsulki o przedluzonym uwalnianiu
Pharmaceutical Form: Capsule
Sponsors
Instytut ,,Pomnik-Centrum Zdrowia Dziecka"
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of Gaucher's disease - GD1-PD (presence of at least 2 clinical features characteristic of early signs of Parkinson's disease: resting tremor, hypomimia, dysarthria, salivation, freezing, ataxia/ gait disturbance, sleep disturbance, cognitive impairment, speech impairment, pyramidal disorder) or GD3 - confirmed by molecular test result 2. Age 10-65 years 3. Signing the informed consent to participate in the study by the patient or, in the case of a minor patient, by parents or legal guardians 4. Stable over the last year hematological parameters (peripheral blood counts, INR), biochemical parameters (transaminases, creatinine) and biomarkers (chitotriosidase, lyso-GL1) 5. Fixed dose of enzyme therapy for at least 1 year and unchanged during study period 6. The use of ABX in the 12 months prior to the study enrollment (group I) 7. Failure to use ABX at all before entering the study (group II) Are the trial subjects under 18? yes Number of subjects for this age range: 4 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Hypersensitivity to the active substance or any of the auxiliary substances 2. Genetically determined states of auxiliary substance intolerance (fructose intolerance, glucose-galactose malabsorption syndrome, sucrase-isomaltase deficiency). 3. Renal impairment (eGFR <90 ml / min) 4. Liver Injury: ALT or AST 2.5 times of ULN 5. Peptic ulcer disease of the stomach or duodenum 6. Pregnancy, breast-feeding or the refusal to use effective methods of contraception or sexual continence during the study in women of childbearing age 7. Use of another study drug within 6 months prior to study enrollment or participation in other studies at the time of enrollment 8. Swallowing disorders or inability to take the study drug orally
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of the study is to analyze the use of ambroxol in patients with certain genotypes of Gaucher disease, to assess the safety and clinical improvement, taking into account biomarkers, molecular mechanisms at the level of methylome and transcriptome (RNA and small RNA), the effect on methylation and metabolomic indicators, and to verify this effect in protein model.;Secondary Objective: Assessment of methylation, RNA expression and metabolome after inclusion and withdrawal of ambroxol;Primary end point(s): 1. Clinical status of patients with Gaucher disease (GD1-PD and GD3) defined as a reduction in mSST scores of neurological symptoms after 90 and 180 days of ABX treatment compared to baseline values. 2. Clinical status of patients with Gaucher disease (GD3), defined as an increase in the mSST score of neurological symptoms 30 days after discontinuation of ABX. 3. Improvement in hematological parameters (normalization of hemoglobin concentration, normalization of platelet count, normalization of INR values) after 90 and 180 days of ABX treatment compared to baseline values 4. Reduction in chitotriosidase activity and lyso- (GL1) levels after 90 and 180 days of ABX treatment compared to baseline values 5. Improvement in bone density after 180 days of ABX treatment compared to baseline values 6. Safety of the drug used;Timepoint(s) of evaluation of this end point: 1. after 90 and 180 days of ABX treatment compared to baseline values 2. after 30 days of ABX discontinuation 3. after 90 and 180 days of ABX treatment relative to baseline values 4. after 90 and 180 days of ABX treatment relative to baseline values 5. after 180 days of ABX treatment relative to baseline values | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Assessment of methylation, RNA expression and metabolome;Timepoint(s) of evaluation of this end point: After 90 and 180 days of ABX treatment compared to baseline values in group II and 30 days after ABX withdrawal in group I | — |
Countries
Poland
Contacts
Public ContactDariusz Rokicki
Instytut ,,Pomnik-Centrum Zdrowia Dziecka"
Outcome results
None listed