Protocol Summary

Protocol No.: OCR15335

Sponsor Protocol No.: PEDS015

Protocol Title.: The Hemophilia Ultrasound Project

Principal Investigator: Wynn, Tung

Objective: To evaluate the prevalence of subclinical arthropathy in children with severe hemophilia undergoing a prophylaxis regimen and without evidence of target joints, using a validated ultrasound scoring method.

Description: Persons with Hemophilia (A or B) often experience recurrent joint bleeds, most commonly affecting the ankles, knees and elbows. These bleeds can lead to significant pain and disability over time. If recurrent joint bleeds are not managed with prompt and adequate infusions of factor concentrate, the damage caused by the presence of blood in the joint space will eventually result in a condition called debilitating chronic hemophilic arthropathy. The initiation of and adherence to a prophylactic infusion regimen, starting with the first or second joint bleed, is essential for prevention of progression to arthropathy. Studies have demonstrated that prophylaxis with recombinant or plasma-derived factor VIII or IX concentrates is effective in preventing clinical joint bleeds and the progression to debilitating joint disease in patients with severe hemophilia A or B respectively. However, for patients on prophylaxis, the absence of symptomatic joint bleeds and/or structural and functional abnormalities of joints on physical examination and plain radiographic images can lead to the erroneous assumption that the prophylaxis is completely effective. It has been established that patients with severe hemophilia are still at risk for subclinical bleeding ("microbleeds") despite seemingly adequate prophylaxis. Young adults, despite a lifetime on prophylaxis and apparently normal joints are developing arthropathy in their 20's and 30's. Prophylaxis as currently practiced may only be delaying the onset of clinical joint disease. The recent advancements in ultrasound imaging (US) have been proven to be effective in confirming a joint bleed, monitoring the evolution of a joint bleed and assessing the resolution or recurrence of a bleed. Previous studies have evaluated the prevalence of subclinical arthropathy in young hemophilic adults using both US and MRI techniques and concluded that US is as effective and sensitive as MRI identifying these subclinical joint abnormalities. However, to the investigators' knowledge, no prior studies have used US technique over an extended period of time to monitor the natural evolution of joint arthropathy in children with hemophilia who are adherent to an established prophylaxis regimen and have no evidence of clinical joint compromise. The seminal Joint Outcome Study, which confirmed the role of prophylaxis in preventing overt clinical joint disease, mandated a trough residual factor VIII level of 1%. While this trough level significantly decreased overt hemarthroses and joint damage, the evidence suggestive of microbleeds raised a question as to the protection afforded by such a low trough level. Intuitively it would seem as if a higher trough level should confer greater protection against microbleeds, and result in more sustainable joint health. The "ideal" protective trough, has not been established. The investigators' hypothesis is that US is a valuable imaging technique to monitor the natural evolution of hemophilic arthropathy in children with severe hemophilia A or B who are undergoing prophylaxis regimen and do not manifest clinical evidence of hemophilic arthropathy. Through this observational study, the investigators will provide valuable information in regards the prevalence, progression and severity of joint abnormalities. The use of US to detect microbleeds before the cumulative damaging effects demonstrable by MRI, will also allow tailoring of treatment and the implementation of new prophylaxis strategies.

Phase: N/A

Age Group: Children

Age: N/A - 30 Months

Gender: All

Scope: National

Treatment:

: Severe Hemophilia A or B
Medical history, physical exam, vital signs,physical therapist targeted exam and ultrasound joint assessment (ankles and knees) every 6 months. MRI joint assessment (knees and ankles) at End of Trial Visit (Month 60).

: Mild/Moderate Hemophilia A or B
Medical history, physical exam, vital signs,physical therapist targeted exam and ultrasound joint assessment (ankles and knees) every year. MRI joint assessment (knees and ankles) at End of Trial Visit (Month 60).

Detailed Eligibility:

Mild, Moderate and Severe Hemophilia A & B patients.

Applicable Conditions:

  • Pediatric Hemophilia A
  • Pediatric Hemophilia B
  • Participation Institution:

  • UF Gainesville : Melissa Lingis
  • Contact:
    Melissa Lingis
    Phone: +1 352-294-8556
    Email: melissa.lingis@peds.ufl.edu

    More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT02807753