Imaging of Arthropathy in Boys With Hemophilia in China

Andrea Doria49 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Hemophilia

Interventions

Study groupDIAGNOSTIC_TEST

Subjects will have physical, imaging examinations and provide samples for biological markers

Eligibility

Sex: MALEMin age: 4 YearsMax age: 11 Years

Medical Language ↔ Plain English

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).

Locations (1)

Beijing Children's Hospital

Beijing, China

Outcomes

Primary Outcomes

Annualized total index joint bleeding rates (AJBRs)

AJBRs will be calculated from prospectively collected joint bleeding logs and clinic records.

Time frame: Between baseline and 24 months

Secondary Outcomes

Number of participants with joint inflammation

Assessed by ultrasound

Time frame: At baseline, 6 months and 24 months

Number of participants with joint inflammation

Assessed by MRI of the joints

Time frame: Between baseline and 24 months

Number of participants with joint damage

Assessed by ultrasound

Time frame: At baseline, 6 months and 24 months

Number of participants with joint damage

Assessed by MRI of the joints

Time frame: 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).

Time frame: Every 6 months

Presence of inflammatory biomarkers in plasma

Measured by ELISA (enzyme-linked immunosorbent assay)

Time frame: 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)

Data from ClinicalTrials.gov

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