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Ultrasonography in Hemophilic Joint Disease and Serum Markers

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ClinicalTrials.gov Identifier: NCT02634918
Recruitment Status : Recruiting
First Posted : December 18, 2015
Last Update Posted : April 5, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
University of California, San Diego
Information provided by (Responsible Party):
Suchitra Acharya, Northwell Health

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 disease when compared to those without (2). Since ultrasound can detect these new vessel changes in the hemophilic synovium in hemophilia patients with joint disease and hemophilia patients with joint disease demonstrate elevated markers of new vessel formation these investigators would now like to determine whether radiological findings of hemophilic joint disease correlate with serological angiogenic markers. This may enable the development of biomarkers for hemophilic joint disease.

Findings from this study will enable the development of ultrasound as a user friendly tool in the hemophilia clinic in order to understand whether every pain and swelling in a joint is actually a joint bleed or soft tissue bleed and to monitor for joint changes to institute or augment scheduled factor infusions ( prophylaxis). This will also result in significant improvement in quality of life with tailored prophylaxis .


Condition or disease Intervention/treatment
Hemophilia A Hemophilia B Hemarthroses Other: ultrasound

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Ultrasonography in Hemophilic Joint Disease
Study Start Date : January 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Ultrasound
3 groups of hemophilia patients - Those with > 20 bleeds into a joint, those with < 2 bleeds into a joint and those with no bleeds into a joint will be enrolled into the study
Other: ultrasound
ultrasound will be performed in hemophilia boys with a history of 20 joint bleeds- Group I, less than 2 joint bleeds into a joint -Group II and no joint bleeds- Group III

those with < 2 bleeds into a joint and
3 groups of hemophilia patients Group I - Those with > 20 bleeds into a joint, Group II - those with < 2 bleeds into a joint and Group III - those with no bleeds into a joint will be enrolled into the study
Other: ultrasound
ultrasound will be performed in hemophilia boys with a history of 20 joint bleeds- Group I, less than 2 joint bleeds into a joint -Group II and no joint bleeds- Group III

those with no bleeds into a joint will be enrolled into the st
3 groups of hemophilia patients Group I - Those with > 20 bleeds into a joint, Group II - those with < 2 bleeds into a joint and Group III - those with no bleeds into a joint will be enrolled into the study
Other: ultrasound
ultrasound will be performed in hemophilia boys with a history of 20 joint bleeds- Group I, less than 2 joint bleeds into a joint -Group II and no joint bleeds- Group III




Primary Outcome Measures :
  1. 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



Secondary Outcome Measures :
  1. 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 ]
    Blood will be collected on the smae day of the study to measure synovial angiogenesis markers- VEGF, MMP-9, SDF-1, HIF-1 , endothelial progenitor cells and hematopoietic progenitor cells


Biospecimen Retention:   Samples Without DNA
plasma samples for angiogenic and cartilage degradation markers


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Boys with hemophilia and inherited bleeding disorders with and without a history of hemarthroses
Criteria

Inclusion Criteria:

  1. All children ages 6 months - 18 years with hemophilia A or B
  2. Hemophilia subjects with and without a history of hemarthroses including target joints ( joint of interest) and joints without documented bleeds( control joints)
  3. Hemophilia subjects with a history of inhibitor to FVIII or FIX and documented hemarthroses
  4. History of hemarthroses more than 4 weeks prior to study enrolment to allow for resolution of hemarthroses which could affect detection of synovial and cartilage changes

Exclusion Criteria:

  1. Bleeding disorder subjects without a diagnosis of hemophilia
  2. Hemophilia subjects with any underlying illness such as liver or renal disease or any systemic illness such as diabetes or any other chronic illness apart from the hemophilia
  3. Hemophilia subjects on medications which could increase bleeding risk such as non steroidal anti inflammatory agents, anti seizure medications apart from factor concentrates
  4. History of hemarthroses within the 4 weeks prior to study enrolment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02634918


Locations
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United States, New York
Feinstein Institute of Medical Research Northwell Health Recruiting
New Hyde Park, New York, United States, 11040
Contact: Suchitra S. Acharya, M.D.    718-470-7380    sacharya@northwell.edu   
Contact: Maria Narine, CPNP    718-470-7380    mmnarine@northwell.edu   
Sponsors and Collaborators
Northwell Health
National Cancer Institute (NCI)
University of California, San Diego

Publications of Results:

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Responsible Party: Suchitra Acharya, Professor of Pediatrics, Northwell Health
ClinicalTrials.gov Identifier: NCT02634918     History of Changes
Other Study ID Numbers: #15-145
First Posted: December 18, 2015    Key Record Dates
Last Update Posted: April 5, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Suchitra Acharya, Northwell Health:
ultrasound,
ultrasonography
hemophilic joint
Doppler

Additional relevant MeSH terms:
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Joint Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Musculoskeletal Diseases
Hemorrhage
Hemophilia A
Hemophilia B
Hemarthrosis
Pathologic Processes