Gait Examination in Patients With Hemophilia in Austria
Condition: Hemophilia
MeSH terms: Hemophilia A
Study type: Observational

Summary: 
      Hemophilia is an inherited disease caused by deficiency in varying degrees of clotting
      factors VIII and IX. Depending on the percentage of clotting factor in the blood the disease
      is categorized as "severe" (<1%, characterized by spontaneous bleedings), "moderate" (1-5%)
      and "mild" (>5%). If untreated, recurrent bleeding into the synovial joints often results in
      irreversible damage due to destruction of the cartilages and progressive joint impairment.

      3d-gait analysis has been demonstrated as valid method to assess abnormal gait patterns and
      to monitor disease progression in patients with hemophilia (PWH). Furthermore, its outcomes
      facilitate the design of individually tailored therapeutic programs. In contrast to
      radiological examinations, 3d-gait analyses take place under weight-bearing conditions, which
      is a relevant issue in terms of weight-induced pain.

      This study aims to explore the applicability of 3-d gait analysis as biomarker (gait
      deviation index) for functional impairments in PWH. Besides 3-d gait scores, secondary
      endpoints such as biomarkers reflecting cartilage damage and a laterality-ratio of leg muscle
      mass (in the case of one-sided target joints) will be tested for their ability to detect
      functional impairments in young adults with hemophilia.

      Based on sample size calculation, 24 subjects aged 16-49 years, able to walk without aids or
      assistance will be included in each of the two groups: control (healthy, male), PWH (severe
      or moderate, treated prophylactically). Subjects suffering from functional impairments caused
      by other conditions than hemophilia, patients with bleedings within 30 days prior to the
      examination, PWH treated with immune-tolerance therapy and/or not successfully treated
      present or past high-titer factor VIII or FIX inhibitor will be excluded.

      Subjects will pass through a set of examinations (medical history, clinical examination,
      3d-gait analysis, anthropometrics, body composition analysis, venipuncture, and urine
      sampling) and carry an accelerometer device for seven consecutive days.

      Confounder adjusted group differences will be assessed by ANCOVA with contrasts and
      Bonferroni correction. Correlations between the applied examination approaches will be
      assessed.

      An evidence based health promotion program including follow-up examinations, physical
      activity promotion, and tailored physiotherapy are being envisaged as a follow-up project
      (JOSEPHA phase 2).
    


Intervention name(s): 3-d gait examination (level walking); Anthropometrics and body composition assessment; Biomarkers; Clinical examination; Habitual physical activity tracking (accelerometer based)
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test
Intervention description(s): Instrumented 3d-gait-analysis will be carried out in the movement lab of the FH (Fachhochschule; University of Applied Sciences) Campus Wien - University of Applied Sciences. The system used is a 10 camera T40S Vicon system with two floor-mounted AMTI OR6/7-2000 force plates. For assessing gait the Plug-in-Gait Lower Body Model with 14 mm retroreflective skin-mounted markers is implemented in the capturing software Vicon Nexus 2.2. The specific parameters will be extracted from the reporting software Vicon Polygon 4.2.
Markers will be placed by one experienced examiner. Subjects will be instructed to walk barefoot on a 10 meters walkway at self-paced walking speed until five right and five left valid first force plate strikes are captured.; Body height will be measured with the stadiometer Seca 213 to the next 0.1cm. Body size and weight will be measured without shoes and outerwear. A correction of 1 kg will be subtracted for clothing. Body weight and body composition will be assessed with the medical body composition analyzer Seca mBCA 515 based on bioelectric impedance analysis.; Blood will be collected into Vacuette serum-separating tubes and will be kept at room temperature for 30 min. Samples will be centrifuged at 1500g for 10 min and serum aliquots will be stored at 80 C until use. Urine samples will be collected into Vacuette tubes containing no additive from non-fasted individuals between 8:00 and 12:00 a.m. Urine samples will be kept at 4 °C for a maximum of 8 h, and then aliquoted and stored at 80 °C.
All biomarkers (except vitamin D and CRP) will be measured in duplicates using standard enzyme-linked immunosorbent assay (ELISA) kits. Serum samples will be assessed for the level of sCOMP, sC1,2C, and sCS846, IL-6, IL-1, sTNFR1 and sTNFR2. Vitamin D and CRP will be measured using automated immunoassay. In urine samples uCTX-II will be determined and these levels will be corrected for creatinine levels (Jaffé method, in-house validated method).; Hemophilia joint health score (HJHS) will be assessed. Height will be measured with a stadiometer (SECA 213), weight with a medical scale (Marsden M-420) and leg length according to the Plug-in-Gait protocol with a measuring tape from the Anterior Spina Iliaca Superior to the distal aspect of the Medial Malleolus. Further anthropometrical parameters taken will be knee distance and malleoli distance by using a caliper. Gait relevant passive joint ROM of the knee, hip and ankle will be assessed by means of a handheld goniometer. The flexibility of hamstring muscles will be expressed as Popliteal Angle measured with a goniometer with the subjects supine and the hip in 90° flexion.; Participants will be instructed to wear an Actigraph wGT3X-BT tri-axial accelerometer permanently over a period of seven consecutive days with an elastic band on right hand sided hip. Data will be process with software ActiLife version 6.13. Cut-offs of at least 10 hours daily wear-time and a minimum of three valid weekdays and one valid weekend day will be applied for data cleaning. Count sampling epoch will be set at one minute. The so called Freedson Adult VM2 Cut-Offs will be applied to categorize physical activity intensities. The so called Freedson VM3 Combination will be applied for the estimation of activity energy expenditure.
Other intervention name(s): Vicon; ActiGraph GT9X Link
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Test group population will be recruited at the clinical hemophilia center and pediatric
        unit of the Medical University of Vienna (patients with hemophila have biannual
        appointments)

        Test group participants are asked to invite a friend at the same age (+/- 3 years; between
        16 and 45y) to participate in the sense of a peer-matched control
      
Biospecimen description: 
      blood, urine
    
Keywords: gait; motion capture; hemophilia joint health score; physical activity; body composition; gait deviation index; hemophilia