<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/NCT03307954</url>
  </required_header>
  <id_info>
    <org_study_id>STH19034</org_study_id>
    <nct_id>NCT03307954</nct_id>
  </id_info>
  <brief_title>Bone Mineral Density Ekso Therapy Study</brief_title>
  <official_title>Feasibility Study to Investigate the Potential Reduction of Bone Mineral Density Loss in Spinal Cord Injured Patients Using Ekso Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheffield Teaching Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sheffield Teaching Hospitals NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Spinal cord injury (SCI) leads to rapid and profound bone loss with large decreases in bone&#xD;
      mineral density (BMD) below the level of the lesion. Decreases in BMD of ~2% per month from&#xD;
      the lower limbs have been reported and rates of loss are maximal over the first two years. As&#xD;
      a consequence, there is an increased risk of fragility fractures particularly of the lower&#xD;
      limbs including an increased risk of hip fracture. Lower limb fragility fractures affect up&#xD;
      to 35% of patients following SCI. These fractures are associated with considerable morbidity&#xD;
      and an increase in mortality.&#xD;
&#xD;
      This single centre UK study will determine if it is feasible to carry out a randomised&#xD;
      controlled BMD study in the acute SCI patient population. The study will compare the BMD of&#xD;
      patients who receive Ekso Therapy (powered exoskeleton device) verse patients who receive&#xD;
      usual physiotherapy alone (control group). It will address patient recruitment rates and&#xD;
      reasons for withdrawal from the study and highlight any practicality issues with study&#xD;
      conduct. It will also provide preliminary data on the effects of Ekso Therapy on BMD,&#xD;
      biochemistry and bone turnover markers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are an estimated 40,000 people living with a Spinal Cord Injury (SCI) in the UK alone&#xD;
      (http://www.apparelyzed.com/statistics.html).&#xD;
&#xD;
      Spinal cord injury (SCI) leads to rapid and profound bone loss with large decreases in bone&#xD;
      mineral density (BMD) below the level of the lesion (Frey-Rindova et al., 2000). Decreases in&#xD;
      BMD of ~2% per month from the lower limbs have been reported and rates of loss are maximal&#xD;
      over the first two years (Jiang et al., 2005). Bone loss is associated with increased bone&#xD;
      resorption and remodelling imbalance which is thought to be due to the combined effects of&#xD;
      immobility together with neurogenic effects. As a consequence, there is an increased risk of&#xD;
      fragility fractures particularly of the lower limbs including an increased risk of hip&#xD;
      fracture. Lower limb fragility fractures affect up to 35% of patients following SCI. These&#xD;
      fractures are associated with considerable morbidity and an increase in mortality.&#xD;
&#xD;
      BMD is conventionally measured using dual-energy x-ray absorptiometry (DXA). This technique&#xD;
      enables measurement of bone mineral content, projected area and areal BMD at the lumbar spine&#xD;
      and proximal femur. DXA does not allow differentiation between cortical and trabecular bone&#xD;
      and does not have the ability to examine microstructural change. High resolution peripheral&#xD;
      quantitative computed tomography (HR-pQCT) is a novel technique which enables changes in&#xD;
      trabecular and cortical microstructure to be evaluated. Using HR-pQCT it is possible to&#xD;
      detect changes in surrogate measures of bone strength in response to loss of weight bearing&#xD;
      activity over just 6 weeks (Kazakia et al, 2014).&#xD;
&#xD;
      To date, there is no established intervention which has been demonstrated to prevent or&#xD;
      reverse bone loss and fractures in this clinical setting. Small studies have suggested that&#xD;
      anti-resorptive agents including bisphosphonates (Bryson et al., 2009) and denosumab (Gifre&#xD;
      et al., 2015) have potential to protect against bone loss following SCI. Physical therapy&#xD;
      using vibration was ineffective (Dudley-Javoroski et al., 2015) as was an ambulation&#xD;
      programme undertaken late in the management of SCI (Needham-Shropshire et al., 1997). Once&#xD;
      bone loss has occurred, it appears to be at best only partially reversible on recovery of&#xD;
      lower limb function. It has been postulated that weight-bearing activity on its own&#xD;
      (Dionyssiotis et al., 2015) or perhaps in combination with anti-resorptive treatment has the&#xD;
      potential to preserve or improve bone health following SCI.&#xD;
&#xD;
      In 2014, a new therapy service called 'Ekso Therapy' was introduced at the Sheffield Princess&#xD;
      Royal Spinal Injuries Centre. Ekso is a revolutionary powered exoskeleton device, which is&#xD;
      strapped on to patients with a SCI to enable them to stand and walk. The device is&#xD;
      manufactured by Ekso Bionics and is CE marked. It has been reported to be a good form of&#xD;
      exercise allowing patients to stretch, and is claimed to be beneficial for muscle strength,&#xD;
      bone health, bowel and bladder function and circulation and has a positive psychological&#xD;
      impact. None of these claims have been investigated or proven in large clinical trials.&#xD;
&#xD;
      This single centre UK study will therefore determine if it is feasible to carry out a&#xD;
      randomised controlled bone study in the acute SCI patient population using the Ekso device.&#xD;
      Investigators will compare the BMD of acute SCI patients before and after they receive a&#xD;
      programme of Ekso Therapy alongside their usual physiotherapy and compare it to patients who&#xD;
      receive standing therapy with usual physiotherapy alone (control group).&#xD;
&#xD;
      It will address patient recruitment rates and reasons for withdrawal from the study and&#xD;
      highlight any practicality issues with study conduct. It will also provide preliminary data&#xD;
      on the effects of Ekso Therapy on bone mineral density, biochemistry and bone turnover&#xD;
      markers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 6, 2016</start_date>
  <completion_date type="Actual">September 14, 2017</completion_date>
  <primary_completion_date type="Actual">September 14, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomised controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of valid data sets</measure>
    <time_frame>2 years recruitment plus 3 months FU</time_frame>
    <description>10 valid data sets (5 in each arm)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants recruited</measure>
    <time_frame>2 years</time_frame>
    <description>Recruitment of 20 patients over 2 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events according to the study protocol</measure>
    <time_frame>Up to 2 years plus 3 months FU</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone Mineral Density</measure>
    <time_frame>Week 0 and Week 12</time_frame>
    <description>Measurement of spine, radius, ulna and hip BMD using DXA and tibia and radius BMD using hp-pqCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone Biochemistry</measure>
    <time_frame>Week 0 and Week 12</time_frame>
    <description>Measurement of bone profile biochemistry, Vitamin D and PTH.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone Biomarkers</measure>
    <time_frame>Week 0, Week 4, Week 8 and Week 12</time_frame>
    <description>Measurement of P1NP and CTX</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Spinal Cord Injuries</condition>
  <arm_group>
    <arm_group_label>Ekso Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Up to 12 weeks of Ekso Therapy. Three sessions per week. One hour per session</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Up to 12 weeks of usual physiotherapy care. Three sessions per week. One hour per session.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Ekso Therapy (Exoskeleton Suit)</intervention_name>
    <arm_group_label>Ekso Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Usual Physiotherapy</intervention_name>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18-70 years old inclusive&#xD;
&#xD;
          -  Traumatic and non-traumatic incomplete tetraplegic or paraplegic patient following&#xD;
             acute SCI injury&#xD;
&#xD;
          -  Be able to provide written informed consent or verbal consent in the presence of an&#xD;
             independent witness&#xD;
&#xD;
          -  Stable medical condition&#xD;
&#xD;
          -  Independently transfer from a wheelchair to a regular chair ideally by completing a&#xD;
             &quot;lift and shift&quot; manoeuvre or a standing pivot transfer.&#xD;
&#xD;
          -  Currently undertaking an active standing programme with a standing frame i.e. Oswestry&#xD;
             Standing Frame, for longer than 15 minutes for inpatients&#xD;
&#xD;
          -  Sufficient upper limb function to be able to grasp and release objects in the hands&#xD;
             with or without use of 'Active hands'.&#xD;
&#xD;
          -  Sufficient range of movement to tolerate sit to stand and normal walking.&#xD;
&#xD;
          -  Sufficient upper extremity strength and sitting balance to assist with balance in&#xD;
             standing with a frame and or crutches.&#xD;
&#xD;
          -  Sufficient lower extremity bone density to stand in standing frame and walk in&#xD;
             traditional orthotics&#xD;
&#xD;
          -  Motor complete paralysis (Asia A) C7 or below&#xD;
&#xD;
          -  Incomplete motor paralysis (Asia C) C2 or below&#xD;
&#xD;
          -  Weigh 220 pounds (100 kilograms) or less&#xD;
&#xD;
          -  Between 5'2&quot; and 6'4&quot; (157 to 188 cm) tall&#xD;
&#xD;
          -  Standing hip width of 17.5&quot; or less.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Aged less than 18 years old&#xD;
&#xD;
          -  Lack the mental capacity to consent&#xD;
&#xD;
          -  Ventilated patients&#xD;
&#xD;
          -  Significant upper or lower limb contractures / spasticity&#xD;
&#xD;
          -  Currently participating in another research study which may have an impact on the&#xD;
             study or patient safety and well-being.&#xD;
&#xD;
          -  Range of motion restrictions that would prevent clients from achieving a normal,&#xD;
             reciprocal gait pattern, or would restrict clients completing normal sit-to-stand or&#xD;
             stand-to-sit transitions&#xD;
&#xD;
          -  Spinal instability&#xD;
&#xD;
          -  Unresolved deep vein thrombosis (DVT)&#xD;
&#xD;
          -  Decreased standing tolerance due to orthostatic hypotension&#xD;
&#xD;
          -  Significant osteoporosis that prevents safe standing or may increase the risk of&#xD;
             fracture caused by standing or walking&#xD;
&#xD;
          -  Previous lower limb fractures less than 6 months ago.&#xD;
&#xD;
          -  Uncontrolled spasticity&#xD;
&#xD;
          -  Uncontrolled Autonomic Dysreflexia (AD)&#xD;
&#xD;
          -  Insufficient upper extremity strength to assist with balance with frame or crutches&#xD;
&#xD;
          -  Leg length discrepancy above recommended values. (Upper leg length discrepancy greater&#xD;
             than half an inch (&gt; .5&quot;) or lower leg discrepancy greater than three-quarters of an&#xD;
             inch (&gt;.75&quot;) )&#xD;
&#xD;
          -  Skin integrity issues on contact surfaces of the device or on surfaces that would&#xD;
             prohibit sitting&#xD;
&#xD;
          -  Cognitive impairments resulting in motor planning or impulsivity concerns&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Ability to mobilise further than 10m on the parallel bars or with use of a walking&#xD;
             aid.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Northern General Hospital</name>
      <address>
        <city>Sheffield</city>
        <zip>S5 7AU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>October 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 12, 2017</study_first_posted>
  <last_update_submitted>April 12, 2018</last_update_submitted>
  <last_update_submitted_qc>April 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03307954
org study id: STH19034
nct id: NCT03307954
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Spinal cord injury (SCI) leads to rapid and profound bone loss with large decreases in bone
      mineral density (BMD) below the level of the lesion. Decreases in BMD of ~2% per month from
      the lower limbs have been reported and rates of loss are maximal over the first two years. As
      a consequence, there is an increased risk of fragility fractures particularly of the lower
      limbs including an increased risk of hip fracture. Lower limb fragility fractures affect up
      to 35% of patients following SCI. These fractures are associated with considerable morbidity
      and an increase in mortality.

      This single centre UK study will determine if it is feasible to carry out a randomised
      controlled BMD study in the acute SCI patient population. The study will compare the BMD of
      patients who receive Ekso Therapy (powered exoskeleton device) verse patients who receive
      usual physiotherapy alone (control group). It will address patient recruitment rates and
      reasons for withdrawal from the study and highlight any practicality issues with study
      conduct. It will also provide preliminary data on the effects of Ekso Therapy on BMD,
      biochemistry and bone turnover markers.
There are an estimated 40,000 people living with a Spinal Cord Injury (SCI) in the UK alone
      (http://www.apparelyzed.com/statistics.html).

      Spinal cord injury (SCI) leads to rapid and profound bone loss with large decreases in bone
      mineral density (BMD) below the level of the lesion (Frey-Rindova et al., 2000). Decreases in
      BMD of ~2% per month from the lower limbs have been reported and rates of loss are maximal
      over the first two years (Jiang et al., 2005). Bone loss is associated with increased bone
      resorption and remodelling imbalance which is thought to be due to the combined effects of
      immobility together with neurogenic effects. As a consequence, there is an increased risk of
      fragility fractures particularly of the lower limbs including an increased risk of hip
      fracture. Lower limb fragility fractures affect up to 35% of patients following SCI. These
      fractures are associated with considerable morbidity and an increase in mortality.

      BMD is conventionally measured using dual-energy x-ray absorptiometry (DXA). This technique
      enables measurement of bone mineral content, projected area and areal BMD at the lumbar spine
      and proximal femur. DXA does not allow differentiation between cortical and trabecular bone
      and does not have the ability to examine microstructural change. High resolution peripheral
      quantitative computed tomography (HR-pQCT) is a novel technique which enables changes in
      trabecular and cortical microstructure to be evaluated. Using HR-pQCT it is possible to
      detect changes in surrogate measures of bone strength in response to loss of weight bearing
      activity over just 6 weeks (Kazakia et al, 2014).

      To date, there is no established intervention which has been demonstrated to prevent or
      reverse bone loss and fractures in this clinical setting. Small studies have suggested that
      anti-resorptive agents including bisphosphonates (Bryson et al., 2009) and denosumab (Gifre
      et al., 2015) have potential to protect against bone loss following SCI. Physical therapy
      using vibration was ineffective (Dudley-Javoroski et al., 2015) as was an ambulation
      programme undertaken late in the management of SCI (Needham-Shropshire et al., 1997). Once
      bone loss has occurred, it appears to be at best only partially reversible on recovery of
      lower limb function. It has been postulated that weight-bearing activity on its own
      (Dionyssiotis et al., 2015) or perhaps in combination with anti-resorptive treatment has the
      potential to preserve or improve bone health following SCI.

      In 2014, a new therapy service called 'Ekso Therapy' was introduced at the Sheffield Princess
      Royal Spinal Injuries Centre. Ekso is a revolutionary powered exoskeleton device, which is
      strapped on to patients with a SCI to enable them to stand and walk. The device is
      manufactured by Ekso Bionics and is CE marked. It has been reported to be a good form of
      exercise allowing patients to stretch, and is claimed to be beneficial for muscle strength,
      bone health, bowel and bladder function and circulation and has a positive psychological
      impact. None of these claims have been investigated or proven in large clinical trials.

      This single centre UK study will therefore determine if it is feasible to carry out a
      randomised controlled bone study in the acute SCI patient population using the Ekso device.
      Investigators will compare the BMD of acute SCI patients before and after they receive a
      programme of Ekso Therapy alongside their usual physiotherapy and compare it to patients who
      receive standing therapy with usual physiotherapy alone (control group).

      It will address patient recruitment rates and reasons for withdrawal from the study and
      highlight any practicality issues with study conduct. It will also provide preliminary data
      on the effects of Ekso Therapy on bone mineral density, biochemistry and bone turnover
      markers.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomised controlled trial
primary purpose: Treatment
masking: None (Open Label)
measure: Number of valid data sets
time frame: 2 years recruitment plus 3 months FU
description: 10 valid data sets (5 in each arm)
measure: Number of participants recruited
time frame: 2 years
description: Recruitment of 20 patients over 2 years
measure: Number of participants with treatment-related adverse events according to the study protocol
time frame: Up to 2 years plus 3 months FU
measure: Bone Mineral Density
time frame: Week 0 and Week 12
description: Measurement of spine, radius, ulna and hip BMD using DXA and tibia and radius BMD using hp-pqCT
measure: Bone Biochemistry
time frame: Week 0 and Week 12
description: Measurement of bone profile biochemistry, Vitamin D and PTH.
measure: Bone Biomarkers
time frame: Week 0, Week 4, Week 8 and Week 12
description: Measurement of P1NP and CTX
arm group label: Ekso Therapy
arm group type: Experimental
description: Up to 12 weeks of Ekso Therapy. Three sessions per week. One hour per session
arm group label: Control
arm group type: Active Comparator
description: Up to 12 weeks of usual physiotherapy care. Three sessions per week. One hour per session.
intervention type: Device
intervention name: Ekso Therapy (Exoskeleton Suit)
arm group label: Ekso Therapy
intervention type: Other
intervention name: Usual Physiotherapy
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Spinal Cord Injuries
sharing ipd: No