<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02229331</url>
  </required_header>
  <id_info>
    <org_study_id>3DMKFM_haemo1</org_study_id>
    <nct_id>NCT02229331</nct_id>
  </id_info>
  <brief_title>Biomechanical Determinants and Patterns Associated to the Pathophysiological Cascade of Ankle Arthropathy in Children With Haemophilia: Non-invasive In-vivo Measurement of Foot Joints in Children With Haemophilia During Gait.</brief_title>
  <acronym>3DMKFM</acronym>
  <official_title>Biomechanical Determinants and Patterns Associated to the Pathophysiological Cascade of Ankle Arthropathy in Children With Haemophilia: Non-invasive In-vivo Measurement of Foot Joints in Children With Haemophilia During Gait.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Haemophilia is a rare X chromosome-linked coagulation disorder resulting from a congenital&#xD;
      deficiency or absence of circulating factor VIII (Haemophilia A) or factor IX (Haemophilia&#xD;
      B).As a consequence, patients with haemophilia are unable to generate adequate thrombin&#xD;
      resulting in abnormal bleeding. Approximately 80-90% of bleeding episodes occur in the&#xD;
      musculoskeletal system, especially in the large synovial joints and muscles. Repeated&#xD;
      haemarthrosis induce joint cartilage damage and irreversible degenerative joint disease.&#xD;
&#xD;
      Regular intravenous administration of coagulation factor concentrates starting after the&#xD;
      first joint bleed and/or before the age of 2 ('primary' prophylaxis) is now the&#xD;
      evidence-based, first-choice treatment in children with severe haemophilia. This primary&#xD;
      prophylaxis has radically decreased the incidence of arthropathy in patients with&#xD;
      haemophilia. Despite the positive effect of primary prophylaxis on arthropathy at several&#xD;
      joints, the ankle joint seems to be an exception to the rule, as patients with haemophilia&#xD;
      treated with primary prophylaxis still experience ankle arthropathy. As such, the ankle now&#xD;
      is the main affected joint in patients with haemophilia under the age of 20. This makes the&#xD;
      scientific community facing a new challenge. Determining aetiologic/contributing factors&#xD;
      associated to the ankle arthropathy pathophysiological cascade in children with haemophilia&#xD;
      (CwH) is therefore a primary objective in the haemophilic research community nowadays.&#xD;
&#xD;
      Loading of the ankle is crucial as the ankle plantar flexors provide the main propulsive&#xD;
      power during gait, the tibiotalar joint caries a complex distribution of joint stresses as a&#xD;
      consequence of talar morphology and kinematics and, from a biomechanical and biochemical&#xD;
      viewpoint, differs significantly from other major lower limb joints. Previous biomechanical&#xD;
      studies focused on kinematic and strength measures, however, they omitted to incorporate&#xD;
      fundamental measures of joint loading (joint kinetics) and joint structural integrity (JSI,&#xD;
      assessment of soft tissue and osteochondral integrity through MRI). This makes it impossible&#xD;
      to draw firm conclusions on biomechanical contributing factors. Furthermore, few, low-quality&#xD;
      studies focused on conservative treatment strategies (e.g. strength training, mobilisation,&#xD;
      proprioceptive training) in patients with ankle arthropathy. In a minority of the cases,&#xD;
      important adverse effects (joint bleeding during strength and proprioception training) have&#xD;
      been reported. Because of the low quality of the intervention studies and the lack of&#xD;
      biomechanical studies focusing on joint loading and joint integrity, it is impossible to&#xD;
      pinpoint the aetiology of these side effects. One assumption might be that side effects&#xD;
      originate from inappropriate conservative approaches as a consequence of lacking knowledge on&#xD;
      joint loading and joint integrity.&#xD;
&#xD;
      An innovative approach within the domain of ankle arthropathy in CwH is therefore to study&#xD;
      foot and lower limb kinetics during gait. The quantification of foot joints kinetics&#xD;
      encompasses considerable challenges and, until recently, only simplified single-segment foot&#xD;
      models have been used. Those models typically underestimate the mechanical contribution of&#xD;
      the different foot joints and, of equal importance, overestimate the kinetic contribution of&#xD;
      the tibiotalar joint.&#xD;
&#xD;
      To overcome the above mentioned shortcomings, a valid 3D Multisegment Foot Kinetic Model&#xD;
      (3DMFKM) should be developed and introduced within the population of CwH. This is important&#xD;
      as it allows to quantify increased loading at the tibiotalar joint (or other joints) that may&#xD;
      help to explain this ankle arthropathy in these patients. This will have been missed by&#xD;
      previous research due to the consideration of the foot as one entire segment.&#xD;
&#xD;
      Providing a classification system based on these kinetic data would, in a second stage, be a&#xD;
      pertinent and valuable approach as this provides a rationale for designing randomized&#xD;
      controlled trials.&#xD;
&#xD;
      In this perspective, it is also recommended to assess the relationship with other&#xD;
      biomechanical and anatomical determinants, especially if one aims at developing optimal&#xD;
      management and rehabilitation strategies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 9, 2014</start_date>
  <completion_date type="Actual">September 16, 2021</completion_date>
  <primary_completion_date type="Actual">May 16, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Kinetic Joint Classification System outcome measure</measure>
    <time_frame>month 24</time_frame>
    <description>Kinetic Joint classification system encompasses a classification system based on mechanical loading profiles of foot joints measured during barefoot walking</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Instrumentation implementation outcome measure</measure>
    <time_frame>month 12</time_frame>
    <description>Before the Kinetic Joint Classification System can be developed, a number of technical challenges needs to be tackled. Thus, this outcome measure reflects the adequate implementation of measurement technology for assessing gait pattern and mechanical loading of foot joints during walking</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRI and Haemophilia Joint Health Score correlation outcome measure</measure>
    <time_frame>month 24</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">37</enrollment>
  <condition>Haemophilia</condition>
  <condition>Arthropathy</condition>
  <arm_group>
    <arm_group_label>gait analysis</arm_group_label>
    <description>gait analysis</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Gait analysis</intervention_name>
    <arm_group_label>gait analysis</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Children with haemophilia&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged range 6-18 years&#xD;
&#xD;
          -  All levels of severity of haemophilia A or B, and on all types of treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Excluded will be those with an acute bleed within 12 weeks prior to testing and those&#xD;
             with an uncontrolled high titre inhibitor.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <last_update_submitted>May 16, 2023</last_update_submitted>
  <last_update_submitted_qc>May 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universitaire Ziekenhuizen KU Leuven</investigator_affiliation>
    <investigator_full_name>Kevin Deschamps</investigator_full_name>
    <investigator_title>Dr</investigator_title>
  </responsible_party>
  <keyword>haemophilia</keyword>
  <keyword>arthropathy</keyword>
  <keyword>pediatrics</keyword>
  <keyword>ankle</keyword>
  <keyword>biomechanics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Joint Diseases</mesh_term>
    <mesh_term>Hemophilia A</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02229331
org study id: 3DMKFM_haemo1
nct id: NCT02229331
lead sponsor: 
collaborator: 
has dmc: No
Haemophilia is a rare X chromosome-linked coagulation disorder resulting from a congenital
      deficiency or absence of circulating factor VIII (Haemophilia A) or factor IX (Haemophilia
      B).As a consequence, patients with haemophilia are unable to generate adequate thrombin
      resulting in abnormal bleeding. Approximately 80-90% of bleeding episodes occur in the
      musculoskeletal system, especially in the large synovial joints and muscles. Repeated
      haemarthrosis induce joint cartilage damage and irreversible degenerative joint disease.

      Regular intravenous administration of coagulation factor concentrates starting after the
      first joint bleed and/or before the age of 2 ('primary' prophylaxis) is now the
      evidence-based, first-choice treatment in children with severe haemophilia. This primary
      prophylaxis has radically decreased the incidence of arthropathy in patients with
      haemophilia. Despite the positive effect of primary prophylaxis on arthropathy at several
      joints, the ankle joint seems to be an exception to the rule, as patients with haemophilia
      treated with primary prophylaxis still experience ankle arthropathy. As such, the ankle now
      is the main affected joint in patients with haemophilia under the age of 20. This makes the
      scientific community facing a new challenge. Determining aetiologic/contributing factors
      associated to the ankle arthropathy pathophysiological cascade in children with haemophilia
      (CwH) is therefore a primary objective in the haemophilic research community nowadays.

      Loading of the ankle is crucial as the ankle plantar flexors provide the main propulsive
      power during gait, the tibiotalar joint caries a complex distribution of joint stresses as a
      consequence of talar morphology and kinematics and, from a biomechanical and biochemical
      viewpoint, differs significantly from other major lower limb joints. Previous biomechanical
      studies focused on kinematic and strength measures, however, they omitted to incorporate
      fundamental measures of joint loading (joint kinetics) and joint structural integrity (JSI,
      assessment of soft tissue and osteochondral integrity through MRI). This makes it impossible
      to draw firm conclusions on biomechanical contributing factors. Furthermore, few, low-quality
      studies focused on conservative treatment strategies (e.g. strength training, mobilisation,
      proprioceptive training) in patients with ankle arthropathy. In a minority of the cases,
      important adverse effects (joint bleeding during strength and proprioception training) have
      been reported. Because of the low quality of the intervention studies and the lack of
      biomechanical studies focusing on joint loading and joint integrity, it is impossible to
      pinpoint the aetiology of these side effects. One assumption might be that side effects
      originate from inappropriate conservative approaches as a consequence of lacking knowledge on
      joint loading and joint integrity.

      An innovative approach within the domain of ankle arthropathy in CwH is therefore to study
      foot and lower limb kinetics during gait. The quantification of foot joints kinetics
      encompasses considerable challenges and, until recently, only simplified single-segment foot
      models have been used. Those models typically underestimate the mechanical contribution of
      the different foot joints and, of equal importance, overestimate the kinetic contribution of
      the tibiotalar joint.

      To overcome the above mentioned shortcomings, a valid 3D Multisegment Foot Kinetic Model
      (3DMFKM) should be developed and introduced within the population of CwH. This is important
      as it allows to quantify increased loading at the tibiotalar joint (or other joints) that may
      help to explain this ankle arthropathy in these patients. This will have been missed by
      previous research due to the consideration of the foot as one entire segment.

      Providing a classification system based on these kinetic data would, in a second stage, be a
      pertinent and valuable approach as this provides a rationale for designing randomized
      controlled trials.

      In this perspective, it is also recommended to assess the relationship with other
      biomechanical and anatomical determinants, especially if one aims at developing optimal
      management and rehabilitation strategies.
observational model: Cohort
time perspective: Cross-Sectional
measure: Kinetic Joint Classification System outcome measure
time frame: month 24
description: Kinetic Joint classification system encompasses a classification system based on mechanical loading profiles of foot joints measured during barefoot walking
measure: Instrumentation implementation outcome measure
time frame: month 12
description: Before the Kinetic Joint Classification System can be developed, a number of technical challenges needs to be tackled. Thus, this outcome measure reflects the adequate implementation of measurement technology for assessing gait pattern and mechanical loading of foot joints during walking
measure: MRI and Haemophilia Joint Health Score correlation outcome measure
time frame: month 24
arm group label: gait analysis
description: gait analysis
intervention type: Other
intervention name: Gait analysis
arm group label: gait analysis
study pop: 
sampling method: Probability Sample
criteria: 
gender: Male
minimum age: 6 Years
maximum age: 18 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Principal Investigator
investigator affiliation: Universitaire Ziekenhuizen KU Leuven
investigator full name: Kevin Deschamps
investigator title: Dr
mesh term: Joint Diseases
mesh term: Hemophilia A