Gaucher Disease
Conditions
Brief summary
The purpose of this study is to better understand the natural history, clinical outcomes, and biological features of Gaucher disease in patients receiving standard medical care
Detailed description
To define clinical trajectories, biomarkers, and mechanistic correlates of persistent or progressive disease in patients with Gaucher disease receiving standard-of-care therapy. Type 1 Gaucher Disease (Non-Neuronopathic) (GD1) Type 2 Gaucher Disease (Acute Neuronopathic) (GD2) Type 3 Gaucher Disease (Chronic Neuronopathic) (GD3) Specific Aim 1 To characterize pulmonary disease and massive lymphadenopathy in patients with neuronopathic Gaucher disease (GD2-GD3) under standard-of-care therapy. Specific Aim 2 To define determinants of refractory skeletal disease in Gaucher disease using longitudinal clinical observation integrated with patient-derived cellular models. Specific Aim 3 To investigate Gaucher-Parkinson overlap as a model of lipid-mediated neurodegeneration using parallel clinical and mechanistic analyses
Interventions
None listed
Sponsors
Yale University
Sanofi-Yale External Research Collaboration
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Months to 75 Years
Healthy volunteers
No
Inclusion criteria
Aim 1 * Confirmed diagnosis of GD2 or GD3 based on genotype and phenotype * Evidence of pulmonary infiltrative disease and/or mediastinal or mesenteric lymphadenopathy * Receiving or eligible for standard-of-care therapy * Age ≥ 3 months * Ability to provide informed consent (or parental consent with assent as appropriate) Aim2 * ages 10-75 * persistent skeletal disease despite long-term therapy Aim3 * Gaucher disease and clinical features of Parkinson disease * Ability to provide informed consent
Exclusion criteria
Aim 1 * Inability to comply with observational follow-up * Any condition that, in the investigator's judgment, precludes safe participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in pulmonary and lymphatic Gaucher disease burden | Baseline, 6, 12, 24, and 36 months | Within-participant change from baseline in the extent of pulmonary infiltrates and/or lymphadenopathy on chest CT or MRI; |
| Change in oxygen requirements | Baseline, 6, 12, 24, and 36 months | Mean oxygen saturation (SpO₂) |
| Change in pulmonary function measures | Baseline, 6, 12, 24, and 36 months | Changed in forced vital capacity and diffusion capacity |
| Change in bone marrow infiltration | Baseline, 6, 12, 24, and 36 months | Change in bone marrow infiltration on MRI |
| Number of participants that develop or have progression of avascular necrosis | Baseline, 6, 12, 24, and 36 months | Number of participants that develop or have progression of avascular necrosis on MRI |
| Change in bone mineral density | Baseline, 6, 12, 24, and 36 months | Change in bone mineral density measured by DEXA Z-score. Above -2.0: Normal. -2.0 or Lower: Below the expected range. |
| Number of participants with fractures or acute bone crisis | Baseline, 6, 12, 24, and 36 months | Number of participants with fractures or acute bone crisis |
| Change in neurologic manifestations | Baseline, 6, 12, 24, and 36 months | Change in motor and non-motor neurologic manifestations |
| DaTscan score | Baseline, 6, 12, 24, and 36 months | Z-Score Between 0 and -1 is normal, Z-score between -1.5 to -1.8 or lower is abnormal. |
| Mean concentration neurofilament light-chain (NfL) trajectories | Baseline, 6, 12, 24, and 36 months | Mean concentration neurofilament light-chain (NfL) trajectories in pg/ml |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change glucosylsphingosine concentration | Baseline, 6, 12, 24, and 36 months | Mean change glucosylsphingosine concentration pg/ml |
| Mean change chitotriosidase activity | Baseline, 6, 12, 24, and 36 months | Mean change glucosylsphingosine concentration pg/ml |
| Mean change Glycoprotein Non-Metastatic Melanoma Protein B (gpNMB) | Baseline, 6, 12, 24, and 36 months | Mean change glucosylsphingosine concentration pg/ml |
| Mean change complement activation markers | Baseline, 6, 12, 24, and 36 months | Mean change complement activation markers concentration pg/ml |
| Mean change circulating inflammatory cytokine | Baseline, 6, 12, 24, and 36 months | Mean change circulating inflammatory cytokine concentration pg/ml |
| Association between biomarker trajectories and clinical or imaging outcomes | Baseline,12 and 36 months | Association between biomarker trajectories and clinical or imaging outcomes evaluated using correlation and longitudinal regression approaches. These are separate cohort-specific measurements and are not intended to constitute a single validated composite score. Imaging and pulmonary-function measurements will be included when clinically obtained or feasible, consistent with the observational nature of the study. |
Countries
United States
Contacts
CONTACTPramod Yang, BS, CCRG
CONTACTPramod K. Mistry, MD, PhD
PRINCIPAL_INVESTIGATORPramod K Mistry, MD, PhD
Yale University
Outcome results
None listed