Imaging of Arthropathy in Boys With Hemophilia in China

Hemophilia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03914716
• Other study ID #: 1000058500
• Status: Completed
• Phase: N/A
• Start date: March 21, 2018
• Est. completion date: November 30, 2023

Study information

• Verified date: April 2024
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: November 30, 2023
• Est. primary completion date: February 2, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 11 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hemophilia
• Hemophilia A
• Joint Diseases

Intervention

Diagnostic Test:
• Study group
Subjects will have physical, imaging examinations and provide samples for biological markers

Locations

Country	Name	City	State
China	Beijing Children's Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Andrea Doria	Beijing Children's Hospital, Baxalta US Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of participants with joint inflammation	Assessed by ultrasound	At baseline, 6 months and 24 months
Secondary	Number of participants with joint inflammation	Assessed by MRI of the joints	Between baseline and 24 months
Secondary	Number of participants with joint damage	Assessed by ultrasound	At baseline, 6 months and 24 months
Secondary	Number of participants with joint damage	Assessed by MRI of the joints	Between baseline and 24 months
Secondary	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
Secondary	Presence of inflammatory biomarkers in plasma	Measured by ELISA (enzyme-linked immunosorbent assay)	At baseline, 6 months and 24 months
Secondary	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
Secondary	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