Biomarkers Related to Bone in Pediatric Gaucher Disease

Last updated: March 12, 2024
Sponsor: Lysosomal and Rare Disorders Research and Treatment Center, Inc.
Overall Status: Active - Recruiting

Phase

N/A

Condition

Gaucher Disease

Bone Diseases

Treatment

N/A

Clinical Study ID

NCT06116071
23-LDRTC-02
  • Ages 5-21
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

Aims of the observational study is to establish novel blood-based biomarkers for grading bone disease in pediatric patients with Gaucher disease (GD). Patients with clinically confirmed GD: deficient GCase enzyme activity and corresponding genetic analysis will be eligible for enrollment. Levels of Lyso-Gb1, chitotriosidase, and CCL18 will be established for future bone biomarkers correlation analysis. Skeletal involvement will be assessed using standard clinical diagnostic tools, such as skeletal radiology and/or (DEXA). The comparator group will include age-matched healthy controls.

Clinically confirmed patients with GD will be stratified based on their disease severity (Gaucher disease type 1 and Gaucher disease type 3) and bone pathology findings. In addition, given that growth is a dynamic process during the pediatric age group, results will be ascertained with respect to phases of growth, i.e., early childhood, late childhood, adolescent, and young adult age groups. At the conclusion of the study, investigatirs expect to establish specific biomarkers of bone development and pathology in pediatric GD patients.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. The parent or legal guardian and the participant who is eligible to provide assent areable and willing to provide informed consent and assent when applicable.
  2. The participant is 5-21 years of age at the initial visit.
  3. The participant has a confirmed diagnosis of GD type 1 or type 3 (biochemically and/orgenetically).
  4. In the investigator's opinion, the subject is capable of understanding and complyingwith protocol requirements.
  5. The subject or, when applicable, the subject's legally acceptable representative signsand dates a written, informed consent form and any required privacy authorizationprior to the initiation of any study procedures.

Exclusion

Exclusion Criteria:

  1. Any subject who does not meet any of the following criteria will not qualify for thestudy.
  2. Any current active chronic infection such as HIV, Hepatitis B or C.
  3. Pregnancy or breastfeeding for females.

Study Design

Total Participants: 20
Study Start date:
November 25, 2023
Estimated Completion Date:
December 31, 2025

Study Description

Gaucher disease (GD), the most common lysosomal storage disorder, is caused by a deficiency of the enzyme glucocerebrosidase. Clinically, there are three sub-types according to neurological involvement. Type 1 GD (GD1) is non-neuronopathic GD, and GD types 2 and 3 (GD2-3) are neuronopathic forms. Bone involvement includes skeletal structural abnormalities such as Erlenmeyer flask deformities, cystic changes, growth retardation, progressive kyphoscoliosis, osteonecrosis, bone density abnormalities, bone fragility, and pathological fractures occur at a spectrum in different GD clinical types.

While bone crises are rare (often referred to as Gaucher crises), avascular necrosis (AVN) may occur in the pediatric age group with long-term morbidity and is often associated with chronic pain and orthopedic deformities requiring multiple surgical interventions.

As known, the development of the skeleton development (longitudinal and bone mass growth) is subject to both environmental and genetic influences. During childhood, skeletal growth is characterized by rapid bone growth and continues to lengthen bones by adding bone tissue on the epiphyseal plate until adolescence. The thickening of long bones is processed by adding bony tissue to its surface. The process of bone remodeling and repair continues after birth and adulthood.

Bone marrow infiltration and bone remodeling defects termed "Erlenmeyer flask deformity" are the most common GD-related bone diseases. Without intervention directed at GD, bone involvement usually starts before puberty. Moreover, children with severe GD present retarded growth and delayed puberty (<5th percentile in 34% of children). However, the underlying mechanisms of regulation of bone development and related complications in the pediatric age group in GD are not yet fully known. Neither the bone-specific biomarkers nor their relationship regarding growth factors associated with normal bone turnover during the normal growth process have been studied in detail in GD in the pediatric age group. Abnormalities in skeletal growth and bone turnover may be related to the abnormal regulation of some growth factors, for example, the elevation of fibroblast growth factor 23 (FGF23) or inhibition of insulin-like growth factors (IGFs) resulting in bone growth impartment. Moreover, chronic inflammation leads to alterations in the function and differentiation of osteoclasts and osteoblasts, which participate in bone growth and remodeling.

Furthermore, the evaluation of bone involvement could be challenging for the pediatric age group. The marrow replacement due to GD that moves in the opposite direction with the expected disappearance of the red marrow makes it challenging to evaluate the bone marrow using MRI and requires experience and technical skills to interpret the imaging studies. In addition, the technique of bone density evaluation is still not uniform in children, especially for different age groups.

Connect with a study center

  • Lysosomal and Rare disorder research and treatment center

    Fairfax, Virginia 22030
    United States

    Active - Recruiting

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