<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/NCT02250365</url>
  </required_header>
  <id_info>
    <org_study_id>H-4-2014-012</org_study_id>
    <nct_id>NCT02250365</nct_id>
  </id_info>
  <brief_title>Electrical Stimulation of the Paretic Upper Limb in the Early Stroke Phase</brief_title>
  <official_title>Electrical Somatosensory Stimulation of the Paretic Upper Limb in Acute Stroke Patients - a Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bispebjerg Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Region Capital Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lundbeck Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bevica Fonden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Manager Jacob Madsen and his wife, Olga Madsen's Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Danish Association of Occupational Therapist</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Copenhagen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the effect of electrical somatosensory stimulation (ESS) on the&#xD;
      restoration of upper limb functioning in acute stroke patients. The effect will be measured&#xD;
      at the end of the intervention and six months post-stroke. We expect that ESS facilitates the&#xD;
      restoration of upper limb functioning and the brain reorganization following stroke.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Introduction&#xD;
&#xD;
           Globally, stroke is ranked as the second leading cause of death and the third largest&#xD;
           cause of disease burden. Stroke is associated with tremendous physical, psychological&#xD;
           and economical demands on patients, families, the health care system and society at&#xD;
           large. The worldwide burden of stroke is expected to increase in the coming years. In&#xD;
           the developed countries, this trend is primarily a consequence of the growing older&#xD;
           population; age being a major risk factor for stroke. Upper limb paresis is one of the&#xD;
           most frequent and persisting impairments following stroke, and represents a major&#xD;
           obstacle to regain independence in activities of daily living (ADL). In fact, it has&#xD;
           been estimated that about 50% of the stroke survivors will be left with a non-functional&#xD;
           arm after completed stroke rehabilitation. In order to minimize the disease burden in&#xD;
           stroke survivors, it is of great importance to design and implement effective&#xD;
           rehabilitation strategies targeting the paretic upper limb.&#xD;
&#xD;
           Studies have shown that recovery of upper limb functioning (i.e. recovery of impairments&#xD;
           and activity limitations, including skills) follows a pattern with a pronounced early&#xD;
           post-stroke recovery and a subsequent leveling off already by 6 months post-stroke. In&#xD;
           fact, it has been shown that 80% of patients reached a plateau within 3 weeks, and 95%&#xD;
           reached a plateau by 9 weeks. It has also been shown that regaining hand dexterity is&#xD;
           largely defined within the first 4 weeks after stroke , indicating a critical time&#xD;
           window for recovery of upper limb functioning. Therefore rehabilitation efforts in the&#xD;
           early post-stroke phase are likely decisive to maximize functional recovery. However,&#xD;
           despite the fact that recovery is most likely in the immediate weeks after stroke, there&#xD;
           are very few studies investigating the effect of therapeutic interventions in this time&#xD;
           period.&#xD;
&#xD;
           Several therapeutic interventions are currently used to try to aid in the recovery of&#xD;
           upper limb functioning. There is limited evidence that hands-on therapy, including&#xD;
           passive joint mobilization, manual stretching of soft tissue and passive exercises, is&#xD;
           effective. Strength training in chronic stroke may reduce motor impairments in patients&#xD;
           with mild-moderate paresis, but without any effect on ADL-performance. Likewise, there&#xD;
           is limited evidence for the use of mirror therapy, sensorimotor and mental training. The&#xD;
           evidence for using orthoses and other supporting devices is inconclusive. Repetitive&#xD;
           task-oriented practice, which is probably the widest used intervention in facilitating&#xD;
           upper limb recovery after stroke, has demonstrated promising results mostly in chronic&#xD;
           stroke when delivered using virtual reality systems and robots, as well as&#xD;
           constrained-induced movement therapy. However, these approaches are patient and resource&#xD;
           demanding in terms of hours of daily training or expensive technologies. Moreover, it&#xD;
           remains unknown if the functional benefits persist at long-term.&#xD;
&#xD;
           Electrical stimulation (ES) is another method that has been used in facilitating the&#xD;
           recovery of upper limb functioning following stroke. ES can induce a muscle contraction,&#xD;
           or it can be a somatosensory stimulation below the motor threshold. Regardless the type&#xD;
           of stimulation, there is some evidence that ES can aid in reducing motor impairments,&#xD;
           but the questions regarding the optimal stimulation protocol (e.g. current amplitude,&#xD;
           pulse frequency, placement of electrodes, treatment duration), long-term effect and&#xD;
           transfer of training effect into ADL remains unanswered. Since this body of evidence is&#xD;
           primarily based upon studies conducted on ES in chronic stroke patients, it also remains&#xD;
           unknown to what extent ES applied in the acute phase after stroke could affect the&#xD;
           recovery of upper limb functioning. Although the vast majority of the studies have&#xD;
           focused on ES that induces muscle contraction, it is widely accepted that somatosensory&#xD;
           input is required for maintaining normal motor function. Research shows that motor&#xD;
           skills acquisition and motor performance are dependent on somatosensory input, and&#xD;
           stroke patients with intact somatosensory function experience more satisfactory response&#xD;
           to rehabilitation. In healthy persons, the application of electrical somatosensory&#xD;
           stimulation (ESS) to peripheral hand nerves, forearm muscles or the whole hand elicits&#xD;
           an increase in the cortical excitability of the representations that control the&#xD;
           stimulated body parts, and the increased cortical excitability seems to outlast the&#xD;
           stimulation period itself. It has been hypothesized that increasing the amount of&#xD;
           somatosensory input may enhance the motor recovery of patients following stroke. Recent&#xD;
           studies in acute, subacute and mostly chronic stroke patients suggest that a single 2&#xD;
           hours-session of ESS to the peripheral hand nerves leads to transient improvement of&#xD;
           pinch force, movement kinematics and upper limb motor skills required for&#xD;
           ADL-performance. The higher the current amplitude, the more prominent the effect seems&#xD;
           to be. ESS is used in conjunction with motor training in only one of these studies. One&#xD;
           study demonstrates that the effect of a single session of ESS is maintained 30 days&#xD;
           after cessation of intervention. Interestingly, there is emerging evidence that multiple&#xD;
           sessions of ESS to the peripheral hand nerves in conjunction with motor training might&#xD;
           improve motor skills of the paretic upper limb in subacute and chronic stroke patients,&#xD;
           and these positive results seems to outlast the intervention period. When ESS is&#xD;
           delivered in multiple sessions, it is unclear which current amplitude is optimal in&#xD;
           subacute stroke patients. ESS of the whole hand using glove electrodes may or may not&#xD;
           benefit the motor recovery of the paretic upper limb in chronic stroke patients.&#xD;
           Importantly, ESS is passive in nature, causes patients minimal discomfort, has no&#xD;
           adverse effects, is relatively cheap and can easily be incorporated in regular practice.&#xD;
           Therefore it is valuable to establish the effect of multiple sessions of ESS in the&#xD;
           restoration of upper limb functioning in the acute phase of stroke.&#xD;
&#xD;
        2. Purpose of the project&#xD;
&#xD;
      The overall aim for the present study is to investigate the effect of multiple sessions of&#xD;
      suprasensory ESS in conjunction with occupational therapy (OT)/physiotherapy (PT) training on&#xD;
      recovery of upper limb functioning in acute stroke patients. Suprasensory ESS is defined as&#xD;
      the highest current amplitude that elicits paresthesia in the absence of discomfort, pain and&#xD;
      visible muscle twitches. Specifically, we wish to address the following:&#xD;
&#xD;
        1. Does continuous, suprasensory ESS in conjunction with OT/PT training:&#xD;
&#xD;
           a) reduce impairments, b) improve motor skills required to ADL-performance, and c)&#xD;
           reduce disability,&#xD;
&#xD;
        2. Are changes that can be observed at the end of the intervention still present by 6&#xD;
           months post-stroke? (long-term effect)&#xD;
&#xD;
      3. Hypotheses&#xD;
&#xD;
      We expect that continuous, suprasensory ESS is more effective than intermittent, suprasensory&#xD;
      ESS. The total time of electrical stimulation during a single, intermittent ESS session will&#xD;
      be 1 minute corresponding to 1/60 of the electrical stimulation time during a single,&#xD;
      continuous ESS session. Furthermore, we expect brain reorganisation to proceed and covariate&#xD;
      with recovery.&#xD;
&#xD;
      4. Methods&#xD;
&#xD;
      4.1. Study participants&#xD;
&#xD;
      The trial subjects will be recruited from patients admitted to the stroke unit of Bispebjerg&#xD;
      Hospital, Copenhagen, Denmark. The stroke unit consists of an acute unit and a rehabilitation&#xD;
      unit, and serves a well-defined urban catchment area with a population of approximately&#xD;
      400,000 citizens.&#xD;
&#xD;
      4.2. Procedure, including recruitment of study participants&#xD;
&#xD;
      All patients consecutively admitted to the rehabilitation stroke unit will be screened for&#xD;
      inclusion and exclusion criteria immediately after admission. Emma Ghaziani, daily project&#xD;
      leader, or other health care personnel involved in the study (e.g. the persons delivering&#xD;
      ESS) will take personal contact to each eligible patient as soon as the patient's medical&#xD;
      condition allows it. The patient is first asked if he/she is interested in receiving&#xD;
      information on the study. If so, the written information is handed out, the information&#xD;
      interview is scheduled, and the patient is informed about the possibility of having a&#xD;
      companion (e.g. a relative, a friend) present at the information interview. If necessary, the&#xD;
      patient may get assistance in contacting the companion in this regard. The information&#xD;
      interview will be performed by Emma Ghaziani or other health care personnel involved in the&#xD;
      study and will take place at the patient's bedside. The patient's bed will be screened off&#xD;
      from the rest of the ward and no other visitors will be present. The declaration of consent&#xD;
      will be collected after the patient has been given a reflection time which is determined with&#xD;
      regard to inclusion criteria d) (i.e. ESS can be initiated within 7 days post-stroke).&#xD;
      Baseline assessment will be performed during the first week post-stroke.&#xD;
&#xD;
      Using a stratified random sampling procedure, the study participants will first be divided&#xD;
      into homogenous subgroups with respect to: a) the ability to perform active finger extension&#xD;
      and b) gender. Active finger extension has shown to be a simple and reliable early predictor&#xD;
      of recovery of upper limb functioning in stroke patients. The patients in each subgroup will&#xD;
      then be randomly assigned to either the continuous or the intermittent group. The therapists&#xD;
      providing OT/PT training and the therapists performing assessments will be blinded to group&#xD;
      allocation. The study participants will be blinded to our hypothesis on which type of&#xD;
      suprasensory ESS is most effective.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 13, 2014</start_date>
  <completion_date type="Actual">August 10, 2017</completion_date>
  <primary_completion_date type="Actual">August 10, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Box and Block Test</measure>
    <time_frame>at 6 months post-stroke</time_frame>
    <description>Performance test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fugl-Meyer Assessment (upper limb section)</measure>
    <time_frame>at hospital discharge, but not later than 4 weeks post-stroke</time_frame>
    <description>Performance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fugl-Meyer Assessment (upper limb section)</measure>
    <time_frame>at 6 months post-stroke</time_frame>
    <description>Performance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hand grip strength</measure>
    <time_frame>at hospital discharge, but not later than 4 weeks post-stroke</time_frame>
    <description>Performance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hand grip strength</measure>
    <time_frame>6 months post-stroke</time_frame>
    <description>Performance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Palmar, lateral and thumb-to-index pinch strength</measure>
    <time_frame>at hospital discharge, but not later than 4 weeks post-stroke</time_frame>
    <description>Performance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Palmar, lateral and thumb-to-index pinch strength</measure>
    <time_frame>6 months post-stroke</time_frame>
    <description>Performance test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale</measure>
    <time_frame>at hospital discharge, but not later than 4 weeks post-stroke</time_frame>
    <description>Interview</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale</measure>
    <time_frame>6 months post-stroke</time_frame>
    <description>Interview</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceptual threshold of touch</measure>
    <time_frame>at hospital discharge, but not later than 4 weeks post-stroke</time_frame>
    <description>Test of sensory function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceptual threshold of touch</measure>
    <time_frame>at 6 months post-stroke</time_frame>
    <description>Test of sensory function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Box and Blocks Test</measure>
    <time_frame>at hospital discharge, but not later than 4 weeks post-stroke</time_frame>
    <description>performance test</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">102</enrollment>
  <condition>Stroke, Acute</condition>
  <arm_group>
    <arm_group_label>Continuous, suprasensory ESS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Intermittent, suprasensory ESS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Continuous, suprasensory ESS</intervention_name>
    <description>1 hour of ESS daily from Monday to Sunday during hospitalization, but no longer than 4th week post-stroke. The ESS will be applied immediately prior to OT/PT training which will include 15 minutes of repetitive, task-oriented upper limb training during the first 30 minutes after cessation of ESS.</description>
    <arm_group_label>Continuous, suprasensory ESS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Intermittent, suprasensory ESS</intervention_name>
    <description>1 hour of ESS daily from Monday to Sunday during hospitalization, but no longer than 4th week post-stroke. The ESS will be applied immediately prior to OT/PT training which will include 15 minutes of repetitive, task-oriented upper limb training during the first 30 minutes after cessation of ESS.</description>
    <arm_group_label>Intermittent, suprasensory ESS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. admission at the rehabilitation stroke unit of Bispebjerg Hospital, Copenhagen,&#xD;
&#xD;
          2. diagnosis of acute stroke (ICD 10 code: 163.9, 161.9),&#xD;
&#xD;
          3. residence in the hospitals' catchment area,&#xD;
&#xD;
          4. age &gt; 18 years,&#xD;
&#xD;
          5. modified Rankin Scale score &lt; 5,&#xD;
&#xD;
          6. ESS can be initiated within 7 days post-stroke,&#xD;
&#xD;
          7. a subscore &lt; 66 on section A-D of Fugl-Meyer Assessment Upper Extremity,&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. presence of cognitive dysfunctions or poor communication skills in Danish that limit&#xD;
             the ability of providing informed consent,&#xD;
&#xD;
          2. have participated in other biomedical, intervention studies within the last 3 months,&#xD;
&#xD;
          3. contraindication to ESS (e.g. pacemaker, significant skin impairment on the paretic&#xD;
             arm),&#xD;
&#xD;
          4. incomplete recovery of the affected upper limb after previous stroke,&#xD;
&#xD;
          5. patients who - because of placement in an institution, incarceration pursuant to the&#xD;
             Psychiatric Act or due to circumstances of employment - are particularly exposed to&#xD;
             pressure regarding participation in the project.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Magnusson, D.Sc</last_name>
    <role>Study Director</role>
    <affiliation>Musculoskeletal Rehabilitation Research Unit and Institute of Sports Medicine, Bispebjerg Hospital &amp; University of Copenhagen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Emma Ghaziani, PhD stud</last_name>
    <role>Principal Investigator</role>
    <affiliation>Musculoskeletal Rehabilitation Research Unit, Bispebjerg Hospital &amp; University of Copenhagen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christian Couppé, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Musculoskeletal Rehabilitation Research Unit and Institute of Sports Medicine, Bispebjerg Hospital &amp; University of Copenhagen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hanne Christensen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bispebjerg Hospital &amp; University of Copenhagen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Volkert Siersma, statistician</last_name>
    <role>Principal Investigator</role>
    <affiliation>Research Unit Of General Practice, Copenhagen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bispebjerg Hospital</name>
      <address>
        <city>Copenhagen</city>
        <state>Zealand</state>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurological Rehabilitation Centre Copenhagen &amp; other rehabilitation and health care institutions</name>
      <address>
        <city>Copenhagen</city>
        <state>Zealand</state>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lioba &amp; Rehabilitation Centre Valby &amp; Heath Centre Stockflethsvej &amp; other rehabilitation and health care institutions</name>
      <address>
        <city>Frederiksberg</city>
        <state>Zealand</state>
        <zip>2000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <last_update_submitted>August 15, 2017</last_update_submitted>
  <last_update_submitted_qc>August 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Copenhagen</investigator_affiliation>
    <investigator_full_name>Emma Ghaziani</investigator_full_name>
    <investigator_title>PhD student</investigator_title>
  </responsible_party>
  <keyword>stroke, acute</keyword>
  <keyword>upper extremity</keyword>
  <keyword>rehabilitation</keyword>
  <keyword>electric stimulation therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02250365
org study id: H-4-2014-012
nct id: NCT02250365
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
This study evaluates the effect of electrical somatosensory stimulation (ESS) on the
      restoration of upper limb functioning in acute stroke patients. The effect will be measured
      at the end of the intervention and six months post-stroke. We expect that ESS facilitates the
      restoration of upper limb functioning and the brain reorganization following stroke.
1. Introduction

           Globally, stroke is ranked as the second leading cause of death and the third largest
           cause of disease burden. Stroke is associated with tremendous physical, psychological
           and economical demands on patients, families, the health care system and society at
           large. The worldwide burden of stroke is expected to increase in the coming years. In
           the developed countries, this trend is primarily a consequence of the growing older
           population; age being a major risk factor for stroke. Upper limb paresis is one of the
           most frequent and persisting impairments following stroke, and represents a major
           obstacle to regain independence in activities of daily living (ADL). In fact, it has
           been estimated that about 50% of the stroke survivors will be left with a non-functional
           arm after completed stroke rehabilitation. In order to minimize the disease burden in
           stroke survivors, it is of great importance to design and implement effective
           rehabilitation strategies targeting the paretic upper limb.

           Studies have shown that recovery of upper limb functioning (i.e. recovery of impairments
           and activity limitations, including skills) follows a pattern with a pronounced early
           post-stroke recovery and a subsequent leveling off already by 6 months post-stroke. In
           fact, it has been shown that 80% of patients reached a plateau within 3 weeks, and 95%
           reached a plateau by 9 weeks. It has also been shown that regaining hand dexterity is
           largely defined within the first 4 weeks after stroke , indicating a critical time
           window for recovery of upper limb functioning. Therefore rehabilitation efforts in the
           early post-stroke phase are likely decisive to maximize functional recovery. However,
           despite the fact that recovery is most likely in the immediate weeks after stroke, there
           are very few studies investigating the effect of therapeutic interventions in this time
           period.

           Several therapeutic interventions are currently used to try to aid in the recovery of
           upper limb functioning. There is limited evidence that hands-on therapy, including
           passive joint mobilization, manual stretching of soft tissue and passive exercises, is
           effective. Strength training in chronic stroke may reduce motor impairments in patients
           with mild-moderate paresis, but without any effect on ADL-performance. Likewise, there
           is limited evidence for the use of mirror therapy, sensorimotor and mental training. The
           evidence for using orthoses and other supporting devices is inconclusive. Repetitive
           task-oriented practice, which is probably the widest used intervention in facilitating
           upper limb recovery after stroke, has demonstrated promising results mostly in chronic
           stroke when delivered using virtual reality systems and robots, as well as
           constrained-induced movement therapy. However, these approaches are patient and resource
           demanding in terms of hours of daily training or expensive technologies. Moreover, it
           remains unknown if the functional benefits persist at long-term.

           Electrical stimulation (ES) is another method that has been used in facilitating the
           recovery of upper limb functioning following stroke. ES can induce a muscle contraction,
           or it can be a somatosensory stimulation below the motor threshold. Regardless the type
           of stimulation, there is some evidence that ES can aid in reducing motor impairments,
           but the questions regarding the optimal stimulation protocol (e.g. current amplitude,
           pulse frequency, placement of electrodes, treatment duration), long-term effect and
           transfer of training effect into ADL remains unanswered. Since this body of evidence is
           primarily based upon studies conducted on ES in chronic stroke patients, it also remains
           unknown to what extent ES applied in the acute phase after stroke could affect the
           recovery of upper limb functioning. Although the vast majority of the studies have
           focused on ES that induces muscle contraction, it is widely accepted that somatosensory
           input is required for maintaining normal motor function. Research shows that motor
           skills acquisition and motor performance are dependent on somatosensory input, and
           stroke patients with intact somatosensory function experience more satisfactory response
           to rehabilitation. In healthy persons, the application of electrical somatosensory
           stimulation (ESS) to peripheral hand nerves, forearm muscles or the whole hand elicits
           an increase in the cortical excitability of the representations that control the
           stimulated body parts, and the increased cortical excitability seems to outlast the
           stimulation period itself. It has been hypothesized that increasing the amount of
           somatosensory input may enhance the motor recovery of patients following stroke. Recent
           studies in acute, subacute and mostly chronic stroke patients suggest that a single 2
           hours-session of ESS to the peripheral hand nerves leads to transient improvement of
           pinch force, movement kinematics and upper limb motor skills required for
           ADL-performance. The higher the current amplitude, the more prominent the effect seems
           to be. ESS is used in conjunction with motor training in only one of these studies. One
           study demonstrates that the effect of a single session of ESS is maintained 30 days
           after cessation of intervention. Interestingly, there is emerging evidence that multiple
           sessions of ESS to the peripheral hand nerves in conjunction with motor training might
           improve motor skills of the paretic upper limb in subacute and chronic stroke patients,
           and these positive results seems to outlast the intervention period. When ESS is
           delivered in multiple sessions, it is unclear which current amplitude is optimal in
           subacute stroke patients. ESS of the whole hand using glove electrodes may or may not
           benefit the motor recovery of the paretic upper limb in chronic stroke patients.
           Importantly, ESS is passive in nature, causes patients minimal discomfort, has no
           adverse effects, is relatively cheap and can easily be incorporated in regular practice.
           Therefore it is valuable to establish the effect of multiple sessions of ESS in the
           restoration of upper limb functioning in the acute phase of stroke.

        2. Purpose of the project

      The overall aim for the present study is to investigate the effect of multiple sessions of
      suprasensory ESS in conjunction with occupational therapy (OT)/physiotherapy (PT) training on
      recovery of upper limb functioning in acute stroke patients. Suprasensory ESS is defined as
      the highest current amplitude that elicits paresthesia in the absence of discomfort, pain and
      visible muscle twitches. Specifically, we wish to address the following:

        1. Does continuous, suprasensory ESS in conjunction with OT/PT training:

           a) reduce impairments, b) improve motor skills required to ADL-performance, and c)
           reduce disability,

        2. Are changes that can be observed at the end of the intervention still present by 6
           months post-stroke? (long-term effect)

      3. Hypotheses

      We expect that continuous, suprasensory ESS is more effective than intermittent, suprasensory
      ESS. The total time of electrical stimulation during a single, intermittent ESS session will
      be 1 minute corresponding to 1/60 of the electrical stimulation time during a single,
      continuous ESS session. Furthermore, we expect brain reorganisation to proceed and covariate
      with recovery.

      4. Methods

      4.1. Study participants

      The trial subjects will be recruited from patients admitted to the stroke unit of Bispebjerg
      Hospital, Copenhagen, Denmark. The stroke unit consists of an acute unit and a rehabilitation
      unit, and serves a well-defined urban catchment area with a population of approximately
      400,000 citizens.

      4.2. Procedure, including recruitment of study participants

      All patients consecutively admitted to the rehabilitation stroke unit will be screened for
      inclusion and exclusion criteria immediately after admission. Emma Ghaziani, daily project
      leader, or other health care personnel involved in the study (e.g. the persons delivering
      ESS) will take personal contact to each eligible patient as soon as the patient's medical
      condition allows it. The patient is first asked if he/she is interested in receiving
      information on the study. If so, the written information is handed out, the information
      interview is scheduled, and the patient is informed about the possibility of having a
      companion (e.g. a relative, a friend) present at the information interview. If necessary, the
      patient may get assistance in contacting the companion in this regard. The information
      interview will be performed by Emma Ghaziani or other health care personnel involved in the
      study and will take place at the patient's bedside. The patient's bed will be screened off
      from the rest of the ward and no other visitors will be present. The declaration of consent
      will be collected after the patient has been given a reflection time which is determined with
      regard to inclusion criteria d) (i.e. ESS can be initiated within 7 days post-stroke).
      Baseline assessment will be performed during the first week post-stroke.

      Using a stratified random sampling procedure, the study participants will first be divided
      into homogenous subgroups with respect to: a) the ability to perform active finger extension
      and b) gender. Active finger extension has shown to be a simple and reliable early predictor
      of recovery of upper limb functioning in stroke patients. The patients in each subgroup will
      then be randomly assigned to either the continuous or the intermittent group. The therapists
      providing OT/PT training and the therapists performing assessments will be blinded to group
      allocation. The study participants will be blinded to our hypothesis on which type of
      suprasensory ESS is most effective.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Box and Block Test
time frame: at 6 months post-stroke
description: Performance test
measure: Fugl-Meyer Assessment (upper limb section)
time frame: at hospital discharge, but not later than 4 weeks post-stroke
description: Performance test
measure: Fugl-Meyer Assessment (upper limb section)
time frame: at 6 months post-stroke
description: Performance test
measure: Hand grip strength
time frame: at hospital discharge, but not later than 4 weeks post-stroke
description: Performance test
measure: Hand grip strength
time frame: 6 months post-stroke
description: Performance test
measure: Palmar, lateral and thumb-to-index pinch strength
time frame: at hospital discharge, but not later than 4 weeks post-stroke
description: Performance test
measure: Palmar, lateral and thumb-to-index pinch strength
time frame: 6 months post-stroke
description: Performance test
measure: Modified Rankin Scale
time frame: at hospital discharge, but not later than 4 weeks post-stroke
description: Interview
measure: Modified Rankin Scale
time frame: 6 months post-stroke
description: Interview
measure: Perceptual threshold of touch
time frame: at hospital discharge, but not later than 4 weeks post-stroke
description: Test of sensory function
measure: Perceptual threshold of touch
time frame: at 6 months post-stroke
description: Test of sensory function
measure: Box and Blocks Test
time frame: at hospital discharge, but not later than 4 weeks post-stroke
description: performance test
arm group label: Continuous, suprasensory ESS
arm group type: Experimental
arm group label: Intermittent, suprasensory ESS
arm group type: Active Comparator
intervention type: Other
intervention name: Continuous, suprasensory ESS
description: 1 hour of ESS daily from Monday to Sunday during hospitalization, but no longer than 4th week post-stroke. The ESS will be applied immediately prior to OT/PT training which will include 15 minutes of repetitive, task-oriented upper limb training during the first 30 minutes after cessation of ESS.
arm group label: Continuous, suprasensory ESS
intervention type: Other
intervention name: Intermittent, suprasensory ESS
description: 1 hour of ESS daily from Monday to Sunday during hospitalization, but no longer than 4th week post-stroke. The ESS will be applied immediately prior to OT/PT training which will include 15 minutes of repetitive, task-oriented upper limb training during the first 30 minutes after cessation of ESS.
arm group label: Intermittent, suprasensory ESS
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter Magnusson, D.Sc
role: Study Director
affiliation: Musculoskeletal Rehabilitation Research Unit and Institute of Sports Medicine, Bispebjerg Hospital & University of Copenhagen
last name: Emma Ghaziani, PhD stud
role: Principal Investigator
affiliation: Musculoskeletal Rehabilitation Research Unit, Bispebjerg Hospital & University of Copenhagen
last name: Christian Couppé, PhD
role: Principal Investigator
affiliation: Musculoskeletal Rehabilitation Research Unit and Institute of Sports Medicine, Bispebjerg Hospital & University of Copenhagen
last name: Hanne Christensen, MD, PhD
role: Principal Investigator
affiliation: Bispebjerg Hospital & University of Copenhagen
last name: Volkert Siersma, statistician
role: Principal Investigator
affiliation: Research Unit Of General Practice, Copenhagen
facility: 
facility: 
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: University of Copenhagen
investigator full name: Emma Ghaziani
investigator title: PhD student
mesh term: Stroke
sharing ipd: Undecided