Brief Summary

There are relatively few data available on type II collagen disorders, and evidence is lacking on the disease course in relation to symptoms and development of complications, the level of actual disease burden over time as well as data to support identification of possible risk factors.

This study aims to build a natural history data set through collection of a number of clinical, imaging, and laboratory assessments that may be specific predictors of type II collagen disorder progression and clinical outcome. Having a type II collagen disorder natural history data set can inform potential efficacy endpoints and biomarkers for future clinical trials.

This natural history study will follow up to 60 individuals diagnosed with a type II collagen disorder for up to 3 years. Visits will be conducted every 3 months for the first year and then every 6 months, during which several assessments will be performed in order to learn about the natural course of the disease, including changes in clinical and functional outcomes, imaging and biofluid biomarkers. Some of the study activities include: a physical exam, height measurements, vision and breathing tests and x-ray. A blood sample will be collected once or twice each year.

Most of the information collected, the tests done, and the schedule of visits in this study are the same as recommended for regular care of children with a type II collagen disorder.

Conditions

• SEDC
• Hypochondrogenesis
• Semd, Strudwick Type
• Kniest Dysplasia

Intervention / Treatment

• Other: Natural History Study

Primary Outcome Measures

• Collection of relevant medical data (retrospective and prospective) (Up to 3 years)
  Collection of demographic data, collagen type II-related medical complications, past medical and surgical history and current medication.
• Anthropometric measurements (Up to 3 years)
  Collection of consistent growth measurements (in centimeters).
• Change over time in motor function in children 2 years old and younger (Up to 2 years)
  Motor development will be assessed using the World Health Organisation (WHO) Motor Milestones.
• Change over time in motor function in children >2 years old (Up to 3 years)
  Timed 100-meter walk/run test (T100T). In the T100T, the participant is instructed to walk as fast as possible for a distance of 100 meters. Timed 10-meter walk/run test (T10T). Participants walk 10-meters at self-selected pace. Functional Mobility Scale (FMS) rates the walking ability in three different walking distances.
• Change over time in pulmonary function (Up to 3 years)
  Lung function measured through spirometry in all participants \>4 years of age
• Change over time in ophthalmological assessment (Up to 3 years)
  Standard ophthalmological assessment.
• Change over time in skeletal abnormalities (Up to 3 years)
  Investigators should collect radiographs according standard of care to determine change in skeletal abnormalities and bone growth.
• Measurement of biomarkers for bone growth (Up to 3 years)
  Changes from baseline in serum collagen X fragments.
• Measurement of CNP/ProCNP (Up to 3 years)
  Changes from baseline in serum CNP/ProCNP
• Measurement of bone-specific alkaline phosphatase (BALP) (Up to 3 years)
  Changes from baseline in serum BALP
• Change in scores for the pediatric quality of life inventory parent report (PedsQL) (Up to 3 years)
  The PedsQL parent-proxy report has 23 items that investigate physical, emotional, and social QoL as well as school functioning.
• Change in PROMIS pediatric short form pain behaviors score (Up to 3 years)
  The PROMIS pediatric short form pain behaviors, parent-proxy report is an 8-item measure completed by parents that assesses pain behaviors displayed by their child in the past 7 days. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10, where higher scores indicate increased behaviors due to pain.
• Change in fatigue (Up to 3 years)
  The PROMIS pediatric fatigue parent-proxy report is completed by parents to assess their child's ability to carry out daily activities.

Countries

France, Spain

Locations and Investigators

• Hopital Necker-Enfants Malades, Paris, France (Recruiting)
  • Valerie Cormier-Daire, MD
  • Mathilde Doyard
• Hospital Universitario La Paz, Madrid, Spain (Recruiting)
  • Maria Saleco Montejo, MD
  • Karen Heath

Study Officials

• Andrea Superti-Furga (Principal Investigator) — Centre hospitalier universitaire vaudois, Lausanne