Advancing Integrated Therapies for Gaucher Disease

Yale University30 enrolled

Overview

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

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

Study Type

OBSERVATIONAL

Enrollment

Conditions

Gaucher Disease

Eligibility

Sex: ALLMin age: 3 MonthsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (1)

Yale New Haven Health System

New Haven, Connecticut, United States

RECRUITING

Outcomes

Primary Outcomes

Change in pulmonary and lymphatic Gaucher disease burden

Within-participant change from baseline in the extent of pulmonary infiltrates and/or lymphadenopathy on chest CT or MRI;

Time frame: Baseline, 6, 12, 24, and 36 months

Change in oxygen requirements

Mean oxygen saturation (SpO₂)

Time frame: Baseline, 6, 12, 24, and 36 months

Change in pulmonary function measures

Changed in forced vital capacity and diffusion capacity

Time frame: Baseline, 6, 12, 24, and 36 months

Change in bone marrow infiltration

Change in bone marrow infiltration on MRI

Time frame: Baseline, 6, 12, 24, and 36 months

Number of participants that develop or have progression of avascular necrosis

Number of participants that develop or have progression of avascular necrosis on MRI

Time frame: Baseline, 6, 12, 24, and 36 months

Change in bone mineral density

Change in bone mineral density measured by DEXA Z-score. Above -2.0: Normal. -2.0 or Lower: Below the expected range.

Time frame: Baseline, 6, 12, 24, and 36 months

Number of participants with fractures or acute bone crisis

Time frame: Baseline, 6, 12, 24, and 36 months

Change in neurologic manifestations

Change in motor and non-motor neurologic manifestations

Central Contacts

Pramod Yang, BS, CCRG

CONTACT

203-785-3412 Ruhua.Yang@yale.edu

Pramod K. Mistry, MD, PhD

CONTACT

2036057878 pramod.mistry@yale.edu

Data from ClinicalTrials.gov

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Secondary Outcomes

Mean change glucosylsphingosine concentration

Mean change glucosylsphingosine concentration pg/ml

Time frame: Baseline, 6, 12, 24, and 36 months

Mean change chitotriosidase activity

Mean change glucosylsphingosine concentration pg/ml

Time frame: Baseline, 6, 12, 24, and 36 months

Mean change Glycoprotein Non-Metastatic Melanoma Protein B (gpNMB)

Mean change glucosylsphingosine concentration pg/ml

Time frame: Baseline, 6, 12, 24, and 36 months

Mean change complement activation markers

Mean change complement activation markers concentration pg/ml

Time frame: Baseline, 6, 12, 24, and 36 months

Mean change circulating inflammatory cytokine

Mean change circulating inflammatory cytokine concentration pg/ml

Time frame: Baseline, 6, 12, 24, and 36 months

Association between biomarker trajectories and clinical or imaging outcomes

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.

Time frame: Baseline,12 and 36 months