Natural History of Morquio B and Late-Onset of GM1 Gangliosidosis

NCT04320329 | Unknown

• 1 other identifier: H18-00155
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Mucopolysaccharidosis type IVB (Morquio-B disease, MBD) is an autosomal-recessive lysosomal disease caused by mutations in a gene called GLB1. Clinically, Morquio B presents with progressive skeletal deformities involving mostly long bones and spine. While the information on GLB1 mutations associated with MBD is limited, there is a significant overlap in clinical presentation between Morquio B and late-onset GM1 gangliosidosis with both conditions being caused by mutations in the same GLB1 gene. In this study, the investigators plan to collect retrospective data from patients' medical charts, as well as, information from the prospective follow up clinic visits. There will be two study visits with the interval of one year. The study procedures will include a detailed physical exam, bone scans, heart and lung function, physical endurance tests, hearing test, laboratory tests and quality of life surveys. The purpose of this study is to collect data on the natural history of Morquio B and to create a biobank of laboratory samples (blood, urine and skin cells) for future research. This information will improve the understanding of the natural progression of Morquio B disease.

Conditions

Morquio B Disease; GM1 Gangliosidosis Type III

Outcome Measures

Primary Outcomes (14)

• Physical Development

  Height

  Through study completion, an average of 1 year

• Physical Development

  Weight

  Through study completion, an average of 1 year

• Physical Development

  Growth rate

  Through study completion, an average of 1 year

• Physical Endurance

  6MWT

  1 year

• Physical Endurance

  3MSCT

  1 year

• Physical Endurance

  Standard Grip Strength evaluation

  1 year

• Range of Motion Scale

  Assessments: shoulder, elbow, wrist, hip, knee, ankle

  Through study completion, an average of 1 year

• Skeletal involvement

  X-ray studies, pQCT (where available), DXA of lateral distal femur, x-ray and/or MRI of cervical spine to assess spinal stenosis and spinal cord compression; X-ray of cervical spine to assess odontoid hypoplasia and atlantoaxial instability

  Through study completion, an average of 1 year

• CNS involvement

  Neurological assessments, Brain MRI

  Through study completion, an average of 1 year

• Surrogate biomarkers

  Glycosaminoglycans (GAGs): keratan sulfate, heparan sulfate, dermatan sulfate, chondroitin-6-sulfate

  Baseline and 1 year

• Surrogate biomarkers

  Comprehensive pro-inflammatory cytokine panel with markers of bone turnover

  Baseline and 1 year

• Health-related Quality of Life (HRQoL)

  SF-36

  Baseline and 1 year

• Health-related Quality of Life (HRQoL) and Activities of Daily living (ADLs)

  MPS-HAQ

  Baseline and 1 year

• Personally Meaningful Outcomes

  PMO Questionnaire

  Baseline and 1 year

Other Outcomes (1)

• Biobank of samples for the future research

  1 year

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients of any age, any gender with no previous HSCT procedure, with a confirmed diagnosis of beta-galactosidase deficiency and who clinically present with skeletal dysostosis with or without CNS involvement.

You may qualify if:

• Confirmed diagnosis of beta-galactosidase deficiency via demonstration of deficient enzyme activity and/or demonstration of homozygous/compound heterozygous pathogenic GLB1 variants;
• Patients diagnosed with beta-galactosidase deficiency and who present with "MPSIVB skeletal phenotype" with or without primary CNS involvement;
• Patient / parent or legal guardian is able to read, understand, and sign the informed consent.

You may not qualify if:

• Previous Hematopoietic Stem Cell Transplant procedure (HSCT);
• Concurrent disease or condition that would interfere with participation in the study and/or travel to the site (for the prospective follow up);
• Previous or current casual treatments that might affect the natural course of the disease;
• Patient's (guardian's) not understanding and/or not agreeing to the informed consent form;
• GM1-gangliosidosis patients who present without "MPSIVB skeletal phenotype"

Sponsors & Collaborators

• University of British Columbia: lead
• Hospital de Clinicas de Porto Alegre: collaborator
• Medical University of Graz: collaborator

Study Sites (1)

BC Children's Hospital

Vancouver, British Columbia, V6H3V4, Canada

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood Urine Dried Blood Spot sample Fibroblasts frozen live cells

MeSH Terms

Conditions

Mucopolysaccharidosis IV; Gangliosidosis, GM1

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Gangliosidoses; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders

Central Study Contacts

Nataliya Yuskiv, Dr

CONTACT

6048752000; nyuskiv@cw.bc.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, MBA, FRCPC

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 25, 2020
• Study Start: June 1, 2020
• Primary Completion: May 31, 2021
• Study Completion: May 31, 2022
• Last Updated: April 30, 2020

Record last verified: 2020-04

Locations

CA (1)