Immune Biomarkers Related to Bone Pathology in Patients With Type 1 Gaucher Disease

Bone-related problems represent the principal unmet medical need in Gaucher disease (GD). 75% of GD type 1 patients develop skeletal complications, including bone remodeling defects, osteopenia, osteoporosis, marrow infiltration, avascular necrosis, and osteolysis. However, the underlying cellular/molecular basis of bone involvement and related complications in GD are not fully known. Neither are there any bone-specific markers associated with individual bone pathology. Early diagnosis of bone disease is the key issue for planning individual therapy to prevent and reverse bone disease in GD.

Study Overview

• Status: Unknown
• Conditions: Gaucher Disease Type 1

Detailed Description

This clinical observational study is designed to identify specific biomarkers for bone involvement in patients with GD1 with decreased bone density and/or bone structural abnormalities

Aims:

1. Identify novel immune cell surface and biochemical markers in peripheral blood correlating with bone involvement in GD.
2. Assess the correlation between cytokine levels in peripheral blood and the severity of bone involvement in GD.
3. Assess the relationship between glycosphingolipids accumulation and macrophage activation with specific bone markers and GD severity.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Jacqueline Fikry; Phone Number: 571-732-4575; Email: jfikry@ldrtc.org
• Study Contact Backup: Name: Margarita Ivanova, PhD; Phone Number: 5715296724; Email: mivanova@ldrtc.org

Study Locations

• United States
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Recruiting
      • LDRTC
      • Contact: Ozlem Goker-Alpan, MD; Phone Number: 703-261-6220; Email: ogokar-alpan@ldrtc.org
      • Contact: Margarita M Ivanova, PhD; Phone Number: 5022957709 7032616220; Email: mivanova@ldrtc.org
      • Sub-Investigator: Margarita Ivanova, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Clinically confirmed GD1 patients will be stratified based on their disease severity and bone density findings.

Description

Inclusion Criteria:

• To be enrolled in this study the subject must meet the following criteria

  1. Subject is greater than 16 years old but not older than 90 years
  2. Signed Informed Consent/Assent
  3. Subject is able and willing to sign informed consent or assent

  4. If the subject has GD1, the must have a confirmed diagnosis of Gaucher disease by

     • GCase enzyme activity
     • DNA analysis demonstrating pathogenic variants in the GBA gene

Exclusion Criteria:

• a) Have evidence of hepatitis B, hepatitis C infection or any other chronic infectious disease b) Be pregnant or breastfeeding

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
GD1 subjects with no bone complications; 1. GD1 subjects with no bone complications (n=10)
GD1 patients with mild bone complication; 2. GD1 subjects with mild bone complications
GD1 with severe bone complications; 3. GD1 subjects with severe bone complications
No bone disease; Controls with no known bone disease (n=10)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure biomarkers level in molar/l/h	Bone homeostasis is dependent on the balance of deposition by osteoblasts DMP-1, OSCAR, Calcitonin, Lyso-GB1, chitotriosidase, CCL18, osteocalcin, BALP, cathepsin K , TRAP 5, RANKL, OPG, DDK-1, sclerostin, MCP1, IL-2, IL-6, IL-10, SRTH2 and TNF-α	18 months
Measure biomarkers level: molar/mg/h	DMP-1, RANK, OSCAR, cathepsin K, OPG	18 months

Collaborators and Investigators

• Sponsor: Lysosomal and Rare Disorders Research and Treatment Center, Inc.
• Investigators: Principal Investigator: Ozlem Goker-Alpan, MD, Lysosomal and Rare Disorders Research and Treatment Center

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Anticipated): April 15, 2020
• Study Completion (Anticipated): May 15, 2020

Study Registration Dates

• First Submitted: August 12, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (Actual): August 14, 2019

Study Record Updates

• Last Update Posted (Actual): August 15, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Osteoporosis; Gaucher disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gaucher Disease
• Other Study ID Numbers: 19-LDRTC-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No