<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/NCT03032718</url>
  </required_header>
  <id_info>
    <org_study_id>2016-01527</org_study_id>
    <nct_id>NCT03032718</nct_id>
  </id_info>
  <brief_title>Whole-body Vibration Training to Reduce the Symptoms of Chemotherapy-induced Peripheral Neuropathy</brief_title>
  <acronym>VANISH</acronym>
  <official_title>Effects of Individually Tailored Whole-body Vibration Training on the Symptoms of Chemotherapy-induced Peripheral Neuropathy: a Randomized-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Basel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>German Sport University, Cologne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital of Cologne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Freiburg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Basel</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>
      Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically&#xD;
      meaningful side effect of cancer treatment. It is induced by neurotoxic chemotherapeutic&#xD;
      agents, causing severe sensory and/or motor deficits such as pain, altered sensation, reduced&#xD;
      or absent reflexes, muscle weakness, reduced balance control, insecure gait, and higher risk&#xD;
      of falling. It is associated with significant disability and poor recovery, not only reducing&#xD;
      patients' autonomy and quality of life but also limiting medical cancer therapy, which&#xD;
      subsequently may affect the clinical outcome and compromise survival. To date, CIPN cannot be&#xD;
      prevented and approved and effective treatment options are lacking.&#xD;
&#xD;
      Promising results regarding CIPN have recently been achieved with exercise. Own preliminary&#xD;
      work revealed that patients profit from sensorimotor training (SMT), experiencing significant&#xD;
      relief from CIPN induced symptoms. In a pilot study we therefore also evaluated whole body&#xD;
      vibration training, a further neuromuscular stimulating exercise intervention. Results&#xD;
      suggest that whole body vibration (WBV) is not only feasible and safe for neuropathic cancer&#xD;
      patients but can attenuate motor and sensory deficits.&#xD;
&#xD;
      We therefore propose a two-armed, multicenter, randomized controlled trial (RCT with a&#xD;
      follow-up period), including 44 patients with neurologically confirmed CIPN, in order to&#xD;
      evaluate the effects of WBV on the relevant symptoms of CIPN. Primary endpoint is the patient&#xD;
      reported reduction of CIPN-related symptoms (FACT-GOG-Ntx). Secondary endpoints will include&#xD;
      compound muscle action potentials, distal motor latency, conduction velocity, and F-waves&#xD;
      from the tibial and peroneal nerve as well as antidromic sensory nerve conduction studies of&#xD;
      the sural nerve, feasibility, non-invasive electromyographic (EMG) activity of mm. tibialis&#xD;
      anterior, soleus, gastrocnemius medialis, rectus femoris, vastus medialis and biceps femoris,&#xD;
      peripheral deep sensitivity, proprioception, balance control as well as pain, quality of life&#xD;
      and the level of physical activity. Patients will be assessed before and after a 12 week&#xD;
      intervention and again after 12 weeks of follow-up. Interim tests will be performed 6 weeks&#xD;
      into the intervention as well as every 3 weeks during the follow-up.&#xD;
&#xD;
      We hypothesize that individually tailored whole body vibration training will reduce relevant&#xD;
      symptoms of CIPN. Our results could contribute to improve supportive care in oncology,&#xD;
      thereby enhancing patients' quality of life and coincidentally enabling the optimal medical&#xD;
      therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Anticipated">July 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2018</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>Single (Outcomes Assessor)</masking>
    <masking_description>Blinding against study arm</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>FACT/GOG-Ntx questionnaire [Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity]</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
    <description>It will be used to document and assess the severity of the subjective peripheral neuropathy (PNP) symptoms. This questionnaire has been validated and is widely applied in clinical practise. It contains eleven items which allow an assessment of the extent of PNP symptoms - from &quot;not at all&quot; to &quot;very much&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compound muscle action potentials (CMAP)</measure>
    <time_frame>Baseline</time_frame>
    <description>obtained from the tibial and peroneal nerve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distal motor latency</measure>
    <time_frame>Baseline</time_frame>
    <description>obtained from the tibial and peroneal nerve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nerve conduction velocity</measure>
    <time_frame>Baseline</time_frame>
    <description>obtained from the tibial and peroneal nerve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensory nerve action potentials (SNAPs)</measure>
    <time_frame>Baseline</time_frame>
    <description>recorded from the lateral malleolus with surface electrodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral deep sensitivity</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
    <description>evaluated with a Rydel-Seiffer tuning fork (128Hz) on a scale from 0 to 8; due to age related neural deconditioning, values ≤4 are pathological for patients ≥ 60years old, while for patients under 60 years old, ≤5 is regarded as pathological</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reflex action</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
    <description>The Achilles tendon reflex as well as the patellar tendon reflex is assessed with a reflex hammer and graded on a 3 point scale (1=agile, 2=weak, 3=missing).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sense of position</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
    <description>This test examines whether patients can recognize a change of position in their first toe, with their eyes closed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perception of touch</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
    <description>The examiner symmetrically strokes the outsides of the patients' legs and feet in order to detect reduced or altered sensation due to demyelination or axonal degeneration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscular strength</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
    <description>The strength of the leg muscles is assessed by requesting the patient to actively move their legs against the resistance of the examiner's arm. The examiner then grades the strength on a six point scale (0=no activity, 1=visual contraction without motor effect, 2=movement under elimination of gravity, 3=movement under gravity, 4=movement against slight resistance 5=normal force).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EMG recordings</measure>
    <time_frame>1 week (first 2 training sessions)</time_frame>
    <description>Normalized (to static standing without vibration condition) integrated EMG activity of mm. tibialis anterior, soleus, gastrocnemius (medial head), mm. rectus femoris, vastus medialis, biceps femoris. EMG recordings will be performed using bipolar Ag/AgCl surface electrodes placed over the mm. soleus, gastrocnemius medialis, tibialis anterior, rectus femoris, vastus medialis and biceps femoris of the right leg. A reference electrode will be placed on the patella. To keep interelectrode resistance below 2 kOhm, the skin areas for the electrodes will have to be shaved, degreased and slightly abraded. The EMG signals will then be transmitted to the amplifier (band-pass filter 10 Hz-1 kHz, 1,0009 amplified) via shielded cables and recorded with 4 kHz.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CIPN-related pain</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
    <description>Visual analogue scale (VAS) in order to assess neuropathic pain as well as the dysesthesias</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postural control</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
    <description>Center of pressure during upright static and dynamic stance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life - questionnaire</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical activity questionnaire</measure>
    <time_frame>Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Chemotherapy-induced Peripheral Neuropathy</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in the intervention group will receive a defined exercise program twice a week in addition to their usual treatment. Training sessions start immediately after randomization and will be supervised by trained sport students. They will take place twice a week, for twelve weeks in specific training rooms designed to meet the needs of oncological patients in the respective centers. The vibration exercises will take place on a side-alternating vibration platform (GalileoTM, Pforzheim, Germany) ®) according to the previously determined optimal (highest neuromuscular response) setting for each individual. Each session will last for about 15 to 30 minutes, leaving sufficient time for regeneration. Training will consist of four vibration exercises, chosen from a standardized pool of exercises with increasing difficulty in order to allow for individual, optimal progression. All sessions will be documented by the supervisor.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients in the control group will receive treatment as usual and will be given the opportunity to participate in the intervention after completion of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Whole-body vibration training</intervention_name>
    <description>Whole-body vibration exercise</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  oncological patients with neurologically confirmed CIPN&#xD;
&#xD;
          -  age: 18-80 years&#xD;
&#xD;
          -  performance status of 0-2 according to the toxicity and response criteria of the&#xD;
             Eastern Cooperative Oncology Group&#xD;
&#xD;
          -  patients underwent neurotoxic chemotherapy with one of the following agents: Taxanes&#xD;
             (docetaxel with a cumulative dose of ≥ 225mg/m2 or paclitaxel with a cumulative dose&#xD;
             of ≥ 525mg/m2), Vinca-alkaloids (vincristine with a cumulative dose of ≥ 4.2mg/m2 or&#xD;
             vinblastine with a cumulative dose of 24mg/m2), Platinum-derivatives (Oxaliplatin with&#xD;
             a cumulative dose of ≥ 510mg/m2, Cisplatinum with a cumulative dose of ≥ 200mg/m2)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pre-existing neuropathy of other cause (e.g. diabetes)&#xD;
&#xD;
          -  given contraindications for WBV (instable osteolysis, osteosynthesis, acute&#xD;
             thrombosis, foot ulcers and a fracture of a lower extremity in the last two years)&#xD;
&#xD;
          -  a myocardial infarction, angina pectoris or heart disease (NYHA III-IV) within the&#xD;
             past six months&#xD;
&#xD;
          -  a mental condition or lack of the German language that prevents the understanding of&#xD;
             the written informed consent&#xD;
&#xD;
          -  metastases of the central nervous system and epilepsy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fiona Streckmann, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Basel</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Oliver Faude, PhD</last_name>
    <phone>0041 61 2074735</phone>
    <email>oliver.faude@unibas.ch</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Fiona Streckmann, PhD</last_name>
    <phone>0041 61 2074713</phone>
    <email>fiona.streckmann@unibas.ch</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Basel</name>
      <address>
        <city>Basel</city>
        <zip>4052</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fiona Streckmann, PhD</last_name>
      <email>fiona.streckmann@unibas.ch</email>
    </contact>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>March 8, 2017</last_update_submitted>
  <last_update_submitted_qc>March 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Basel</investigator_affiliation>
    <investigator_full_name>Oliver Faude</investigator_full_name>
    <investigator_title>Deputy Head Exercise and Movement Science</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</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/NCT03032718
org study id: 2016-01527
nct id: NCT03032718
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically
      meaningful side effect of cancer treatment. It is induced by neurotoxic chemotherapeutic
      agents, causing severe sensory and/or motor deficits such as pain, altered sensation, reduced
      or absent reflexes, muscle weakness, reduced balance control, insecure gait, and higher risk
      of falling. It is associated with significant disability and poor recovery, not only reducing
      patients' autonomy and quality of life but also limiting medical cancer therapy, which
      subsequently may affect the clinical outcome and compromise survival. To date, CIPN cannot be
      prevented and approved and effective treatment options are lacking.

      Promising results regarding CIPN have recently been achieved with exercise. Own preliminary
      work revealed that patients profit from sensorimotor training (SMT), experiencing significant
      relief from CIPN induced symptoms. In a pilot study we therefore also evaluated whole body
      vibration training, a further neuromuscular stimulating exercise intervention. Results
      suggest that whole body vibration (WBV) is not only feasible and safe for neuropathic cancer
      patients but can attenuate motor and sensory deficits.

      We therefore propose a two-armed, multicenter, randomized controlled trial (RCT with a
      follow-up period), including 44 patients with neurologically confirmed CIPN, in order to
      evaluate the effects of WBV on the relevant symptoms of CIPN. Primary endpoint is the patient
      reported reduction of CIPN-related symptoms (FACT-GOG-Ntx). Secondary endpoints will include
      compound muscle action potentials, distal motor latency, conduction velocity, and F-waves
      from the tibial and peroneal nerve as well as antidromic sensory nerve conduction studies of
      the sural nerve, feasibility, non-invasive electromyographic (EMG) activity of mm. tibialis
      anterior, soleus, gastrocnemius medialis, rectus femoris, vastus medialis and biceps femoris,
      peripheral deep sensitivity, proprioception, balance control as well as pain, quality of life
      and the level of physical activity. Patients will be assessed before and after a 12 week
      intervention and again after 12 weeks of follow-up. Interim tests will be performed 6 weeks
      into the intervention as well as every 3 weeks during the follow-up.

      We hypothesize that individually tailored whole body vibration training will reduce relevant
      symptoms of CIPN. Our results could contribute to improve supportive care in oncology,
      thereby enhancing patients' quality of life and coincidentally enabling the optimal medical
      therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Blinding against study arm
measure: FACT/GOG-Ntx questionnaire [Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity]
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
description: It will be used to document and assess the severity of the subjective peripheral neuropathy (PNP) symptoms. This questionnaire has been validated and is widely applied in clinical practise. It contains eleven items which allow an assessment of the extent of PNP symptoms - from "not at all" to "very much".
measure: Compound muscle action potentials (CMAP)
time frame: Baseline
description: obtained from the tibial and peroneal nerve
measure: Distal motor latency
time frame: Baseline
description: obtained from the tibial and peroneal nerve
measure: Nerve conduction velocity
time frame: Baseline
description: obtained from the tibial and peroneal nerve
measure: Sensory nerve action potentials (SNAPs)
time frame: Baseline
description: recorded from the lateral malleolus with surface electrodes
measure: Peripheral deep sensitivity
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
description: evaluated with a Rydel-Seiffer tuning fork (128Hz) on a scale from 0 to 8; due to age related neural deconditioning, values ≤4 are pathological for patients ≥ 60years old, while for patients under 60 years old, ≤5 is regarded as pathological
measure: Reflex action
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
description: The Achilles tendon reflex as well as the patellar tendon reflex is assessed with a reflex hammer and graded on a 3 point scale (1=agile, 2=weak, 3=missing).
measure: Sense of position
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
description: This test examines whether patients can recognize a change of position in their first toe, with their eyes closed.
measure: Perception of touch
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
description: The examiner symmetrically strokes the outsides of the patients' legs and feet in order to detect reduced or altered sensation due to demyelination or axonal degeneration.
measure: Muscular strength
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
description: The strength of the leg muscles is assessed by requesting the patient to actively move their legs against the resistance of the examiner's arm. The examiner then grades the strength on a six point scale (0=no activity, 1=visual contraction without motor effect, 2=movement under elimination of gravity, 3=movement under gravity, 4=movement against slight resistance 5=normal force).
measure: EMG recordings
time frame: 1 week (first 2 training sessions)
description: Normalized (to static standing without vibration condition) integrated EMG activity of mm. tibialis anterior, soleus, gastrocnemius (medial head), mm. rectus femoris, vastus medialis, biceps femoris. EMG recordings will be performed using bipolar Ag/AgCl surface electrodes placed over the mm. soleus, gastrocnemius medialis, tibialis anterior, rectus femoris, vastus medialis and biceps femoris of the right leg. A reference electrode will be placed on the patella. To keep interelectrode resistance below 2 kOhm, the skin areas for the electrodes will have to be shaved, degreased and slightly abraded. The EMG signals will then be transmitted to the amplifier (band-pass filter 10 Hz-1 kHz, 1,0009 amplified) via shielded cables and recorded with 4 kHz.
measure: CIPN-related pain
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
description: Visual analogue scale (VAS) in order to assess neuropathic pain as well as the dysesthesias
measure: Postural control
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
description: Center of pressure during upright static and dynamic stance
measure: Quality of life - questionnaire
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
measure: Physical activity questionnaire
time frame: Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
arm group label: Intervention
arm group type: Experimental
description: Patients in the intervention group will receive a defined exercise program twice a week in addition to their usual treatment. Training sessions start immediately after randomization and will be supervised by trained sport students. They will take place twice a week, for twelve weeks in specific training rooms designed to meet the needs of oncological patients in the respective centers. The vibration exercises will take place on a side-alternating vibration platform (GalileoTM, Pforzheim, Germany) ®) according to the previously determined optimal (highest neuromuscular response) setting for each individual. Each session will last for about 15 to 30 minutes, leaving sufficient time for regeneration. Training will consist of four vibration exercises, chosen from a standardized pool of exercises with increasing difficulty in order to allow for individual, optimal progression. All sessions will be documented by the supervisor.
arm group label: Control
arm group type: No Intervention
description: Patients in the control group will receive treatment as usual and will be given the opportunity to participate in the intervention after completion of the study.
intervention type: Behavioral
intervention name: Whole-body vibration training
description: Whole-body vibration exercise
arm group label: Intervention
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Fiona Streckmann, PhD
role: Principal Investigator
affiliation: University of Basel
last name: Oliver Faude, PhD
phone: 0041 61 2074735
email: oliver.faude@unibas.ch
last name: Fiona Streckmann, PhD
phone: 0041 61 2074713
email: fiona.streckmann@unibas.ch
facility: 
status: Recruiting
contact: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: University of Basel
investigator full name: Oliver Faude
investigator title: Deputy Head Exercise and Movement Science
mesh term: Peripheral Nervous System Diseases
sharing ipd: No