Complement Activation in the Lysosomal Storage Disorders

NCT04189601 | Withdrawn

• 1 other identifier: Royal_Melbourne
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The lysosomal storage disorders (LSDs) are monogenic disorders associated with inflammation affecting multiple organs, and early death. Few treatments are available that can modify the disease course, and there is an urgent need to identify new steps in pathogenesis that can be targeted therapeutically. The complement system is novel and highly plausible as a primary driver of inflammation and cellular injury in the LSDs. This study assesses the complement activation state in patients with Fabry disease (FD), Gaucher disease (GD) and Niemann-Pick disease, type C (NPC), with comparison to healthy controls. This has the potential for immense clinical benefit through targeted complement inhibition across the full spectrum of lysosomal storage disorders, in which key pathophysiological processes including the inflammatory response to lysosomally 'stored' materials are shared.

Conditions

Fabry Disease; Gaucher Disease; Niemann-Pick Disease, Type C; Lysosomal Storage Diseases

Keywords

complement

Outcome Measures

Primary Outcomes (1)

• Change in soluble C5b-9

  Difference in sC5b-9 between Subjects and Controls at a single timepoint up to 8 months

  At baseline

Secondary Outcomes (1)

• Other complement biomarkers

  Difference in C3a and C5a between Subjects and Controls at a single timepoint up to 8 months

Study Arms (2)

Study subjects

Patients with Fabry disease, Gaucher disease, or Niemann-Pick disease, type D

Diagnostic Test: Complement measurements

Controls

Age- and sex-matched to Study subjects

Diagnostic Test: Complement measurements

Interventions

Complement measurements DIAGNOSTIC_TEST

Blood and urine tests to assess the complement activation state

Controls; Study subjects

Eligibility Criteria

• Age: 17 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Consenting patients with FD, GD or NPC, and age and sex-matched controls

You may qualify if:

• All consenting patients with a prior diagnosis of FD, GD or NPC will be included in the study. Control participants will be healthy volunteers.

You may not qualify if:

• Patients who are unable to provide consent or to perform a blood or urine test will be excluded.

Sponsors & Collaborators

• Melbourne Health: lead
• Sanofi: collaborator

Study Sites (1)

The Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

MeSH Terms

Conditions

Fabry Disease; Gaucher Disease; Niemann-Pick Disease, Type C; Lysosomal Storage Diseases

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Niemann-Pick Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Thomas D Barbour, MBBS

  Melbourne Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2019
• First Posted: December 6, 2019
• Study Start: September 30, 2020
• Primary Completion: February 26, 2021
• Study Completion: April 30, 2021
• Last Updated: June 7, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)