Clinical Trial: Longitudinal Study of Bone Disease in Children With Mucopolysaccharidoses (MPS) I, II, and VI

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: Longitudinal Study of Bone and Endocrine Disease in Children With MPS I, II, and VI: A Multicenter Study of the Lysosomal Disease Network.

Brief Summary: Approximately 85% of individuals with Mucopolysaccharidosis (MPS) type I, II, or VI report weekly pain and 50-60% have significant limitations in their activities of daily living due to MPS related musculoskeletal disease despite treatment with enzyme replacement therapy (ERT). Thus there is a critical need to identify additional therapies to alleviate the burden of musculoskeletal disease in order to improve the health and quality of life of individuals with MPS. However, disease progression needs to be quantified to be able to determine efficacy of new therapies. This study is a multi-institutional, 5-year, longitudinal study of musculoskeletal disease in MPS. The objective is to quantitatively describe the progression of skeletal disease and identify biomarkers that either predict disease severity or could be used as therapeutic targets in individuals with MPS I, II, and VI. A database of standardized measurements of musculoskeletal disease in MPS will allow the field to efficiently move forward with therapeutic clinical trials in patients with MPS.

Detailed Summary:

Although children with MPS I, II, and VI who are treated with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT) are now living into adulthood with good cognitive development, their quality of life is significantly impacted by their skeletal abnormalities (i.e., kyphosis, scoliosis, genu valgum), joint contractures, pain, and severe short stature. Additional therapies (e.g., post-HCT supplemental ERT, anti-TNFα drugs, stop codon suppression drugs, gene therapy) to decrease the burden of skeletal disease and improve growth are needed. However, prior to these therapeutic studies, control data quantifying the progression of skeletal disease in individuals with MPS I, II and VI treated with ERT and/or HCT are needed, along with biomarkers to be used as early predictors of response to treatment.

Osteoporosis has been described in animal models of MPS. It is unknown whether abnormalities seen in animal models of MPS can be extrapolated to osteoporosis or increased risk of fracture in children and adults affected with MPS. Preliminary data suggest that children and adolescents with MPS I, II and VI have low bone mineral density (BMD) after adjustment for short stature and abnormal bone geometry and that markers of bone remodeling are cross-sectionally associated with BMD. It is unknown whether this decreased BMD during childhood will result in osteoporosis and increased fracture risk in adulthood. Determining the risk for osteoporosis in MPS I, II and VI has become particularly important as these individuals are now healthier and more mobile with new and improved treatments and thus have a greater opportunity for fracture.

Glycosaminoglycan (GAG) deposition has been identified in bone and cartilage in animal models of MPS. GAG deposition in cartilage has specifically been shown to induce inflamm
Sponsor: Los Angeles Biomedical Research Institute

Current Primary Outcome: Annual change in dual energy x-ray absorptiometry (DXA) [ Time Frame: baseline, year 1, year 2, year 3 ]

Measurement of bone density and body composition


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Annual change in Peripheral quantitative computer tomography (pQCT) [ Time Frame: baseline, year 1, year 2, year 3 ]
    Measurement of volumetric bone density, bone geometry, bone strength, and muscle fat
  • Annual change in Biomarkers of bone remodeling [ Time Frame: baseline, year 1, year 2, year 3 ]
    Measurements of bone turnover
  • Annual change in Biodex [ Time Frame: baseline, year 1, year 2, year 3 ]
    Measurement of muscle strength
  • Annual change in Endocrine function tests [ Time Frame: baseline, year 1, year 2, year 3 ]
    Thyroid function, growth factor levels, pubertal hormones, vitamin D
  • Annual change in growth measurements [ Time Frame: baseline, year 1, year 2, year 3 ]
    sitting and standing heights, arm and tibial length


Original Secondary Outcome: Same as current

Information By: Los Angeles Biomedical Research Institute

Dates:
Date Received: November 11, 2011
Date Started: August 2009
Date Completion: September 2019
Last Updated: May 3, 2017
Last Verified: May 2017