Clinical Trial: Ultrasonography in Hemophilic Joint Disease and Serum Markers
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational
Official Title: Ultrasonography in Hemophilic Joint Disease
Brief Summary:
Hemophilia is a bleeding disorder (deficiency of a blood clotting factor/ protein) resulting in bleeding in joints and muscles. As patients continue to bleed into their joints they develop progressive joint damage leading to joint contractures, disability and days missed from work and school resulting in chronic debilitating pain and compromised quality of life. Current therapy is the administration of the missing protein or factor concentrate on a scheduled basis to prevent bleeding into the joints referred to as prophylaxis. This factor concentrate is expensive ~ $ 3,000 - 6,000 per infusion/ week in a child weighing 20 kg translating into $ 77,000 /yr for life. This regimen has been shown to be effective to prevent joint bleeds but the timing is unclear and not based on adequate evidence. Currently joint damage is diagnosed using MRI which is expensive and requires sedation in children < 6 yrs of age. Therefore there is a need for a user friendly tool such as a ultrasound to monitor for the development of joint disease and tailor treatment based on an individual child's needs. This would also enable differentiating a joint bleed from a soft tissue bleed which present similarly and duration of treatment tends to be longer for a joint bleed. Acharya et al have previously shown that ultrasound is comparable to MRI for the diagnosis of hemophilic joint disease in hemophilia patients over the age of 6 years. However, the diagnostic findings in children < 18 years with hemophilia on ultrasound is not well defined(1).
The hemophilic synovium after repeated joint bleeds reveals the development of new vessels which are fragile and contribute to recurrent joint bleeds. Acharya et al have previously shown that angiogenesis, a process of new vessel formation is active in hemophilic synovium and angiogenic markers were significantly elevated in hemophilic patients with joint
Detailed Summary:
Background: Hemophilic joint disease secondary to recurrent hemarthroses is one of the most disabling and costly complications of hemophilia. Prior to widespread use of prophylactic factor concentrates, children in the United States with severe hemophilia A and B (X-linked recessive disorders with <1% factor VIII/IX (FVIII/FIX) activity) experienced an average of 30-35 hemarthroses per year reported for FVIII deficiency (3,4 ). Clinical and sub clinical hemarthroses during childhood results in synovitis (hypertrophied synovium characterized by villous formation, markedly increased vascularity and chronic inflammatory cells (5) eventually leading to pannus formation and destructive arthritis (6, 7). At this time, synovial bleeding may be related not only to clotting factor deficiency but also to pre-existing vascular damage and inflammation, which is difficult to control clinically. Use of factor concentrate prophylaxis results in hemophilia patients experiencing fewer joint bleeds, less rapid deterioration of joint function and fewer days lost from school or work. However, it may be complicated by the unpredictable development of an inhibitor (a high-affinity, polyclonal, function-neutralizing antibody directed against FVIII/FIX), with an incidence of about 25% and 6% respectively (8) . These individuals have limited treatment options or are treated with products that are less efficacious in treating the joint bleed along with potential deleterious side effects such as thrombogenecity( 9) thus favoring joint disease development.
Primary prophylaxis (infusion of FVIII concentrates (25 - 40 u/kg thrice weekly or FIX concentrates - 80-100u/kg twice a week starting at age 1-2 yrs) before the onset of joint bleeds is used in Sweden since the 1960s to keep the trough level of factor VIII/FIX > 1%, converting a severe hemophilia patient (FVIII/FIX activity <1%) into a m
Sponsor: Northwell Health
Current Primary Outcome: To determine the prevalence rates of synovial and cartilage changes using USG-PDS: [ Time Frame: 12 months ]
Synovial changes on USG- PDS:
Scoring system for synovitis which has 2 components - joint effusion and synovial thickening: Joint effusion will be defined as a compressible anechoic intracapsular area and the amount of fluid will be semiquantitatively scored usinga previosuly described scoring system by Martinoli et al. Quantitative assessment of the power Doppler signal: Power Doppler signal will be assessed subjectively for degree of vascularity -Table 2, Table 2
Degree of Vascularity PDS Signal Score Normal or minimal No signal or local dark red 1 Mild hyperemia Dark red to red 2 Moderate hyperemia Red to orange 3 Marked hyperemia Orange to yellow 4
Original Primary Outcome: Same as current
Current Secondary Outcome: To determine whether the presence/absence of synovial and cartilage changes measured using USG-PDS are associated with any changes in biological surrogate marker levels. [ Time Frame: 15 months ]
Original Secondary Outcome: Same as current
Information By: Northwell Health
Dates:
Date Received: October 8, 2015
Date Started: January 2016
Date Completion: December 2017
Last Updated: July 23, 2016
Last Verified: July 2016
