Imaging of Arthropathy in Boys With Hemophilia in China

Study Overview
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Brief Summary
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Hemophilia is a genetic condition characterized by marked phenotypic heterogeneity. Bleeding into a joint is the single most important risk factor for the development of hemophilic arthropathy (HA). It is thought that clinical and imaging manifestations of HA are at least partially attributable to genetic polymorphisms unrelated to the hemophilia genotype. Identifying and characterizing biologic factors that could explain differences in susceptibility to joint degeneration of patients with hemophilia would help stratify patients according to the risk of degeneration of their joints and develop personalized therapeutic and prophylactic strategies. This study is conducted in China.

Detailed Description
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This will be a 3-year prospective cohort study conducted in a single centre (Beijing Children's Hospital, BCH, China) with a 2-year follow-up of patients Index joints (ankles, elbows and knees) of young Chinese boys with hemophilia A will be evaluated as follows: physical examination every 6 months using the Hemophilia Joint Health Score [HJHS], ultrasound imaging (gray-scale and color Doppler ultrasound [US]), and by laboratory (serum) at baseline, at 6, and 24 months. Magnetic resonance imaging (MRI) scans of index joints will be obtained at baseline, and 24 months. Features that will be captured either quantitatively or semantically in the imaging scans will be aggregated to generate imaging phenotypes which will be associated with clusters of co-expressed genes (metagenes) and clinical data.

Official Title
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Radiogenomics: Personalized Imaging of Arthropathy in Boys With Hemophilia in China

Conditions
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Hemophilia

Intervention / Treatment
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* Diagnostic Test: Study group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hemophilia A with baseline FVIII levels of <2% Clinical history of ≥ 50 exposure days to FVIII prior to the study start. On-demand treatment, prophylaxis FVIII infusions or treatment with plasma-derived products for >3 months prior to enrollment into the study. Exclusion Criteria: History of FVIII inhibitor (titer >0.6 Bethesda Units [BU]) Chronic renal failure (serum creatinine >2.0 mg /dL). Chronic liver disease (alanine aminotransferase [ALT] >200 U/L). Clinically documented immunodeficiency. Anticipation of need for major surgery during the study period. Association of diseases known to mimic or cause joint diseases such as symptomatic human immunodeficiency virus (HIV) infection, juvenile idiopathic arthritis, and metabolic bone diseases. Social barriers for participation in the study such as long distance between home and the comprehensive care centre, and documented track record of non-compliance to therapies or participation in clinical studies. Neuro-developmental/behavioral problems. Contraindications to MR imaging (presence of heart pacemakers, metallic foreign bodies in the eye, aneurysm clips, severe claustrophobia).

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Study group|Subjects will have physical, imaging examinations and provide samples for biological markers|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized total index joint bleeding rates (AJBRs) | AJBRs will be calculated from prospectively collected joint bleeding logs and clinic records. | Between baseline and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with joint inflammation | Assessed by ultrasound | At baseline, 6 months and 24 months | 
| Number of participants with joint inflammation | Assessed by MRI of the joints | Between baseline and 24 months | 
| Number of participants with joint damage | Assessed by ultrasound | At baseline, 6 months and 24 months | 
| Number of participants with joint damage | Assessed by MRI of the joints | Between baseline and 24 months | 
| Number of participants with clinical arthropathy | Assessed by the Hemophilia Joint Health Score tool (HJHS), version 2.1 - Joint score range: 0 (normal) to 16 (worse outcome). | Every 6 months | 
| Presence of inflammatory biomarkers in plasma | Measured by ELISA (enzyme-linked immunosorbent assay) | At baseline, 6 months and 24 months | 
| Internal MRI-based soft tissue score change | Assessed by the 17-point International Prophylaxis Study Group (IPSG) MRI scale. Score range: 0 to 17 (worse outcome) | Between baseline and 24 months | 
| Internal MRI-based osteochondral tissue score change | Assessed by the 17-point International Prophylaxis Study Group (IPSG) MRI scale. Score range: 0 to 17 (worse outcome) | Between baseline and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia, Radiogenomics, Arthropathy