<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/NCT03818074</url>
  </required_header>
  <id_info>
    <org_study_id>012170</org_study_id>
    <nct_id>NCT03818074</nct_id>
  </id_info>
  <brief_title>High Frequency (1000Hz) Spinal Cord Stimulation in Neuropathic Pain Patients With Virgin Back</brief_title>
  <official_title>A Prospective Single Centre Pilot Study to Investigate the Response to 1000Hz Frequency in Patients With Spinal Cord Stimulation With Intractable Neuropathic Pain Who Have Not Undergone Spinal Surgery (Virgin Back)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Barts &amp; The London NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boston Scientific Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Barts &amp; The London NHS Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Spinal Cord stimulation (SCS) is a common intervention used in patients who suffer from&#xD;
      chronic nerve pain following back surgery. This is known as failed back surgery syndrome&#xD;
      (FBSS). Equally, the National Institute of Clinical Excellence (NICE) who work with the NHS,&#xD;
      recommend suitable medicines and treatments for patients in their guidelines; suggest that&#xD;
      SCS can be used in patients who have never had back surgery. The is no outcome data to define&#xD;
      that SCS works in patients with neuropathic back pain, therefore this study will provide&#xD;
      clinical data to see if this works.&#xD;
&#xD;
      SCS delivers mild electrical impulses to the nerves along the spinal cord. This blocks the&#xD;
      pain pathway from reaching the brain. This helps manage the pain experienced the lower back.&#xD;
&#xD;
      A common side effect of the conventional system is that patients may experience 'pins and&#xD;
      needles', tingling, and numbness, known as parathesia at site of stimulation. This can be&#xD;
      particularly uncomfortable for patients. However, parathesia can be eliminated by changing&#xD;
      certain settings on the stimulator. This could include increasing the frequency of the&#xD;
      stimulator known as high frequency (HF). This works by delivering energy to site of&#xD;
      stimulation below the parathesia threshold, so minimal or no parathesia is experienced.&#xD;
&#xD;
      Only one study has been completed previously using HF frequency on patients with FBSS. The&#xD;
      major findings from these studies have found that when compared to conventional SCS (uses a&#xD;
      frequency of 40-80 Hz) that HF has provided better pain relief with minimal or no parathesia.&#xD;
      Higher frequencies parameters are not completely novel because they have been used in&#xD;
      patients who have FBSS. However, settings of 1000Hz which will be used in this study have not&#xD;
      been done in patients who suffer from neuropathic pain and have not had any previous spinal&#xD;
      surgery.&#xD;
&#xD;
      Therefore, the main reason of this study is to investigate the response patients suffering&#xD;
      from neuropathic pain and have not had previous spinal surgery, have to 1000Hz (HF) frequency&#xD;
      spinal cord stimulation. We will also investigate the effect this setting has on the quality&#xD;
      of life of the patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Spinal cord stimulation (SCS) is a successful treatment in patients with intractable&#xD;
      neuropathic pain. This therapy is most commonly used in patients who have chronic neuropathic&#xD;
      pain following failed surgery, known as failed back surgery syndrome (FBSS) . There is&#xD;
      evidence from previous studies to demonstrate that SCS can provide a 50- 70% reduction in&#xD;
      pain medication and pain scores. A randomised controlled study compared SCS with conventional&#xD;
      medical management (CMM). When compared with the CMM group; the SCS patients had a 50% pain&#xD;
      reduction in their back pain and leg pain. The results suggested that patients who received&#xD;
      SCS had better pain relief and health related quality of life over a period of 6 to 12 months&#xD;
      compared to the CMM group. Additionally, these patients reported satisfaction in SCS&#xD;
      treatment, continuous pain relief, and clinical improvements in functional capacity and&#xD;
      health-related quality of life.&#xD;
&#xD;
      On the other hand, SCS has been progressively being used in patients with intractable&#xD;
      neuropathic pain who have not undergone spinal back surgery (&quot;Virgin-back''). The UK NICE&#xD;
      guidelines have recommended SCS as a treatment option for patients with intractable&#xD;
      neuropathic spinal pain, including patients who have not undergone previous spinal surgery&#xD;
      (NICE, 2008).&#xD;
&#xD;
      One of the main drawbacks of conventional SCS is the onset of parathesia, despite being an&#xD;
      effective therapy for neuropathic pain. This can cause abnormal sensations or considerable&#xD;
      discomfort to the patient during activity or sudden position changes. Typically, conventional&#xD;
      SCS operate at frequencies ranging from 40-80 Hz, long pulse widths of 300-500 µsec, and&#xD;
      amplitudes to stimulate patient's pain sensory percept distribution. These frequencies are&#xD;
      often used because sensory perception is often lost at 300 Hz. Current studies have found&#xD;
      that delivering stimulating frequencies below the upper limit of what may cause parathesia;&#xD;
      may reduce discomfort and abnormal sensations, increasing the tolerability of SCS treatment.&#xD;
      Parathesia is considered necessary in order to cover the painful area and provide maximum&#xD;
      pain relief. However recent research suggests that parathesia may not be necessary for pain&#xD;
      relief, and in fact that pain awareness can provide full benefits of SCS.&#xD;
&#xD;
      Data from (PROCO RCT) indicates that similar pain relief and improvement in quality of life&#xD;
      measures are experienced independent of the type of frequency (from 1kHz up to 10kHz) used in&#xD;
      paraesthesia free SCS therapy when the proper target and dose are identified. Further, the&#xD;
      study showed that 1kHz stimulation provides similar pain relief using significantly less&#xD;
      energy than higher frequencies.&#xD;
&#xD;
      High frequency (HF) stimulation is a new promising, new stimulation paradigm involving higher&#xD;
      frequency, lower pulse widths, and lower amplitudes when compared to conventional SCS. The&#xD;
      effectiveness of HF-SCS is controlled by the amount of Neural dose (frequency, amplitude and&#xD;
      pulse width) passing the electrodes and reaching the neural tissue, resulting in minimal&#xD;
      discomfort and damage to the tissues before the definite shape of the impulse.&#xD;
&#xD;
      Pre-clinical Data&#xD;
&#xD;
      A study testing the efficacy of kilohertz and conventional SCS was done on rat models during&#xD;
      different pain conditions. The findings established that higher frequencies can be delivered&#xD;
      at lower amplitudes whilst reversing pain behaviours as seen at 50 Hz and at higher intensity&#xD;
      of motor threshold.&#xD;
&#xD;
      Moreover, both conventional and kilohertz frequency SCS forms intensity and&#xD;
      frequency-dependant inhibition of mechanical hypersensitivity, in animal models of&#xD;
      neuropathic pain. Different intensities (20, 40 and 80% motor threshold) and frequencies (50,&#xD;
      1kHz and 10kHz) were used. At each frequency, the pulse width was constant. It was observed&#xD;
      that as frequency was increased, the pulse density also increased.&#xD;
&#xD;
      Clinical data&#xD;
&#xD;
      Previous randomised control trials have provided evidence that using frequency ≤1200 Hz and&#xD;
      pulses ≤ 5% provides efficient relief with HF- SCS.&#xD;
&#xD;
      A multi-centre trial previously conducted to see the effects of HF-SCS on patients being&#xD;
      delivered up to 10 kHz of stimulation. Patients were assessed for pain ratings, disability,&#xD;
      sleep disturbances, and satisfaction, as well as complication rates for up to six months.&#xD;
      When results were compared to baseline, 88% of patients reported a significant reduction in&#xD;
      mean back visual analogue scores (VAS) from 8.4 to 2.7 at six months. Seventy four per cent&#xD;
      of patients reported more than 50% back pain relief at six months. Overall it was concluded&#xD;
      that individuals in the trial group with chronic back pain, 70% of patients were provided&#xD;
      with positive improvement and experienced sustained low back and leg pain relief. Substantial&#xD;
      improvements were also seen for these patients with disability and sleep disturbances.&#xD;
&#xD;
      If clinically considered, the NRS has substantially reduced in patients who received HF-SCS&#xD;
      than conventional SCS in patients with neuropathic pain and FBSS. This suggests that HF may&#xD;
      provide relief in virgin-back patients. Since there remains limited research in this area&#xD;
      therefore, the main objective of our study is to investigate the response to 1000Hz frequency&#xD;
      following SCS treatment in &quot;virgin back&quot; patients with intractable lower limb neuropathic&#xD;
      pain. However based on the PROCO RCT and further WHISPER trial, we aim to establish role of&#xD;
      microburst and combination therapy in non-responders.&#xD;
&#xD;
      Our sample size of 30 patients will allow detection of minimal important difference of 2.0 on&#xD;
      the NRS pain scale at 90% power and alpha of 5%, assuming an outcome standard deviation of&#xD;
      2.5 and attrition rate at 12-months of 30%. Patient primary and secondary outcomes at each&#xD;
      follow up point will be compared to baseline values. Data analyses will take account of the&#xD;
      paired nature of the data and use non-independent t-test for continuous outcomes and&#xD;
      McNemar's test for binary outcomes.&#xD;
&#xD;
        -  The primary objective is to investigate the clinical response to high frequency&#xD;
           (1,000Hz) in patients who are due to have percutaneous spinal cord stimulation for&#xD;
           intractable lower limb neuropathic pain&#xD;
&#xD;
        -  The secondary objective will be to investigate the effect on functionality and quality&#xD;
           of life and adverse events at the high frequency group (1000Hz)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 9, 2018</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>To investigate the clinical response to high frequency (1,000Hz) in patients who are due to have percutaneous spinal cord stimulation for intractable back and lower limb neuropathic pain</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Patients will be required to adhere to the study and attend all follow up visits. Informed consent and questionnaires will be administered at visit 0. They will be followed up 4, 12, 24 weeks and 12 months, 24 months after their SCS permanent implant. Questionnaires will be administered at each visit.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline numerical Rating Score (NRS) at 4 weeks</measure>
    <time_frame>4 weeks</time_frame>
    <description>NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline numerical Rating Score (NRS) at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline numerical Rating Score (NRS) at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline numerical Rating Score (NRS) at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline numerical Rating Score (NRS) at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Oswestry Disability Index (ODI) scores at 4 weeks</measure>
    <time_frame>4 weeks</time_frame>
    <description>A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Oswestry Disability Index (ODI) scores at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Oswestry Disability Index (ODI) scores at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Oswestry Disability Index (ODI) scores at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Oswestry Disability Index (ODI) scores at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Patient's Global Impression of change (PGIC) scores to 4 weeks</measure>
    <time_frame>4 weeks</time_frame>
    <description>A standard seven point scale would be used to assess the SCS outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Patient's Global Impression of change (PGIC) scores to 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>A standard seven point scale would be used to assess the SCS outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Patient's Global Impression of change (PGIC) scores to 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>A standard seven point scale would be used to assess the SCS outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Patient's Global Impression of change (PGIC) scores to 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>A standard seven point scale would be used to assess the SCS outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Patient's Global Impression of change (PGIC) scores to 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>A standard seven point scale would be used to assess the SCS outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline EQ-5D-5L scores at 4 weeks</measure>
    <time_frame>4 weeks</time_frame>
    <description>The EQ-5D is a standardised instrument used to measure health outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline EQ-5D-5L scores at 3 months</measure>
    <time_frame>3 months.</time_frame>
    <description>The EQ-5D is a standardised instrument used to measure health outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline EQ-5D-5L scores at 6 months</measure>
    <time_frame>6 months.</time_frame>
    <description>The EQ-5D is a standardised instrument used to measure health outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline EQ-5D-5L scores at 12 months</measure>
    <time_frame>12 months.</time_frame>
    <description>The EQ-5D is a standardised instrument used to measure health outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline EQ-5D-5L scores at 24 months</measure>
    <time_frame>24 months.</time_frame>
    <description>The EQ-5D is a standardised instrument used to measure health outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Pain and Sleep 3 point index (PSQ-3) at 4 weeks</measure>
    <time_frame>4 weeks</time_frame>
    <description>The PSQ-3 is an instrument that measures the quality of sleep over a month.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Pain and Sleep 3 point index (PSQ-3) at 3 months</measure>
    <time_frame>3 months</time_frame>
    <description>The PSQ-3 is an instrument that measures the quality of sleep over a month.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Pain and Sleep 3 point index (PSQ-3) at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>The PSQ-3 is an instrument that measures the quality of sleep over a month.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Pain and Sleep 3 point index (PSQ-3) at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>The PSQ-3 is an instrument that measures the quality of sleep over a month.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Pain and Sleep 3 point index (PSQ-3) at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>The PSQ-3 is an instrument that measures the quality of sleep over a month.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Resource Questionnaire at 12 months</measure>
    <time_frame>12 months.</time_frame>
    <description>The resource questionnaire measures the impact of health on employment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Resource Questionnaire at 24 months</measure>
    <time_frame>24 months.</time_frame>
    <description>The resource questionnaire measures the impact of health on employment.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Neuropathic Pain</condition>
  <condition>Low Back Pain</condition>
  <arm_group>
    <arm_group_label>Boston Wavewriter (1000Hz) spinal cord stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To investigate the response to high frequency (1000Hz) in patients who are due to have spinal cord stimulation for neuropathic back pain.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Boston Wavewriter 1000Hz Spinal cord Stimulation</intervention_name>
    <description>High frequency spinal cord stimulation.</description>
    <arm_group_label>Boston Wavewriter (1000Hz) spinal cord stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-70&#xD;
&#xD;
          2. Chronic Back Pain (≥ 6 mo) with NRS ≥ 6/10&#xD;
&#xD;
          3. Back pain predominant over leg pain (if leg pain present)&#xD;
&#xD;
          4. Failure to respond to conventional treatment including intense rehababilitation and&#xD;
             facet/MBB/SI interventions&#xD;
&#xD;
          5. No prior spinal surgery for the back and leg pain on the same site of implantation.&#xD;
&#xD;
          6. Presence of lumbar degenerative disc disease&#xD;
&#xD;
          7. Absence of spinal pathology which would require surgical intervention&#xD;
&#xD;
          8. Stable dose of opioids and anti-neuropathic drugs for ≥ 6 months&#xD;
&#xD;
          9. Patients with intractable lumbar neuropathic pain who are due to receive Percutaneous&#xD;
             Spinal Cord Stimulation as part of their standard treatment per NICE HTA guidance 159&#xD;
             at Barts Health NHS Hospitals.&#xD;
&#xD;
         10. Patients who have given their written informed consent.&#xD;
&#xD;
         11. Female patients of childbearing potential must be using adequate contraception (i.e.&#xD;
             using oral or IM contraception or an IUCD) and must have a negative urine pregnancy&#xD;
             test.&#xD;
&#xD;
         12. Patients must be able to communicate in English in order to complete validated&#xD;
             questionnaires written in English.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients not able to comply or understand the study-related requirements&#xD;
&#xD;
          2. Active alcohol, recreational or prescription drug abuse in the last 3 months.&#xD;
&#xD;
          3. Unwilling to reduce excessive pain medications&#xD;
&#xD;
          4. A medical/psychiatric condition that could interfere with study procedures, accurate&#xD;
             pain reporting, and/or confound study outcomes&#xD;
&#xD;
          5. Patients with diabetes or any current diagnosis of progressive neurological disease&#xD;
             (i.e., CIDP, Multiple sclerosis)&#xD;
&#xD;
          6. Immuno-compromised/high risk for surgical infection&#xD;
&#xD;
          7. Pregnant and/or breast feeding&#xD;
&#xD;
          8. Terminal illness with anticipated survival &lt; 12 months&#xD;
&#xD;
          9. Patients who have been part of a previous spinal cord stimulation trial&#xD;
&#xD;
         10. Currently implanted with an active implantable device(s) (e.g. pacemaker, drug pump,&#xD;
             implantable pulse generator)&#xD;
&#xD;
         11. Untreated clinically significant sleep disorder as judged by the CI.&#xD;
&#xD;
         12. Unresolved issues of secondary gain (i.e., litigation)&#xD;
&#xD;
         13. Participation in another clinical study in the last 30 days that would confound data.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kavita Poply, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Barts &amp; The London NHS Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Vivek Mehta, Dr</last_name>
    <phone>+ 44 203 765 8878</phone>
    <email>vivek.mehta@bartshealth.nhs.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Vivek Health Mehta</name>
      <address>
        <city>London</city>
        <zip>EC1A 4NP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vivek H Mehta, Dr</last_name>
      <phone>02037658876</phone>
      <email>vivek.mehta@nhs.net</email>
    </contact>
    <contact_backup>
      <last_name>Alia Ahmad</last_name>
      <phone>02037658876</phone>
      <email>alia.ahmad1@nhs.net</email>
    </contact_backup>
    <investigator>
      <last_name>Kavita Poply</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>October 5, 2022</last_update_submitted>
  <last_update_submitted_qc>October 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>High Frequency spinal cord stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
    <mesh_term>Low Back Pain</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We will follow the policies laid by the local information governance team at Barts Health NHS Trust and NHS code of Confidentiality in accordance to the data protection act.</ipd_description>
  </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/NCT03818074
org study id: 012170
nct id: NCT03818074
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Spinal Cord stimulation (SCS) is a common intervention used in patients who suffer from
      chronic nerve pain following back surgery. This is known as failed back surgery syndrome
      (FBSS). Equally, the National Institute of Clinical Excellence (NICE) who work with the NHS,
      recommend suitable medicines and treatments for patients in their guidelines; suggest that
      SCS can be used in patients who have never had back surgery. The is no outcome data to define
      that SCS works in patients with neuropathic back pain, therefore this study will provide
      clinical data to see if this works.

      SCS delivers mild electrical impulses to the nerves along the spinal cord. This blocks the
      pain pathway from reaching the brain. This helps manage the pain experienced the lower back.

      A common side effect of the conventional system is that patients may experience 'pins and
      needles', tingling, and numbness, known as parathesia at site of stimulation. This can be
      particularly uncomfortable for patients. However, parathesia can be eliminated by changing
      certain settings on the stimulator. This could include increasing the frequency of the
      stimulator known as high frequency (HF). This works by delivering energy to site of
      stimulation below the parathesia threshold, so minimal or no parathesia is experienced.

      Only one study has been completed previously using HF frequency on patients with FBSS. The
      major findings from these studies have found that when compared to conventional SCS (uses a
      frequency of 40-80 Hz) that HF has provided better pain relief with minimal or no parathesia.
      Higher frequencies parameters are not completely novel because they have been used in
      patients who have FBSS. However, settings of 1000Hz which will be used in this study have not
      been done in patients who suffer from neuropathic pain and have not had any previous spinal
      surgery.

      Therefore, the main reason of this study is to investigate the response patients suffering
      from neuropathic pain and have not had previous spinal surgery, have to 1000Hz (HF) frequency
      spinal cord stimulation. We will also investigate the effect this setting has on the quality
      of life of the patients.
Spinal cord stimulation (SCS) is a successful treatment in patients with intractable
      neuropathic pain. This therapy is most commonly used in patients who have chronic neuropathic
      pain following failed surgery, known as failed back surgery syndrome (FBSS) . There is
      evidence from previous studies to demonstrate that SCS can provide a 50- 70% reduction in
      pain medication and pain scores. A randomised controlled study compared SCS with conventional
      medical management (CMM). When compared with the CMM group; the SCS patients had a 50% pain
      reduction in their back pain and leg pain. The results suggested that patients who received
      SCS had better pain relief and health related quality of life over a period of 6 to 12 months
      compared to the CMM group. Additionally, these patients reported satisfaction in SCS
      treatment, continuous pain relief, and clinical improvements in functional capacity and
      health-related quality of life.

      On the other hand, SCS has been progressively being used in patients with intractable
      neuropathic pain who have not undergone spinal back surgery ("Virgin-back''). The UK NICE
      guidelines have recommended SCS as a treatment option for patients with intractable
      neuropathic spinal pain, including patients who have not undergone previous spinal surgery
      (NICE, 2008).

      One of the main drawbacks of conventional SCS is the onset of parathesia, despite being an
      effective therapy for neuropathic pain. This can cause abnormal sensations or considerable
      discomfort to the patient during activity or sudden position changes. Typically, conventional
      SCS operate at frequencies ranging from 40-80 Hz, long pulse widths of 300-500 µsec, and
      amplitudes to stimulate patient's pain sensory percept distribution. These frequencies are
      often used because sensory perception is often lost at 300 Hz. Current studies have found
      that delivering stimulating frequencies below the upper limit of what may cause parathesia;
      may reduce discomfort and abnormal sensations, increasing the tolerability of SCS treatment.
      Parathesia is considered necessary in order to cover the painful area and provide maximum
      pain relief. However recent research suggests that parathesia may not be necessary for pain
      relief, and in fact that pain awareness can provide full benefits of SCS.

      Data from (PROCO RCT) indicates that similar pain relief and improvement in quality of life
      measures are experienced independent of the type of frequency (from 1kHz up to 10kHz) used in
      paraesthesia free SCS therapy when the proper target and dose are identified. Further, the
      study showed that 1kHz stimulation provides similar pain relief using significantly less
      energy than higher frequencies.

      High frequency (HF) stimulation is a new promising, new stimulation paradigm involving higher
      frequency, lower pulse widths, and lower amplitudes when compared to conventional SCS. The
      effectiveness of HF-SCS is controlled by the amount of Neural dose (frequency, amplitude and
      pulse width) passing the electrodes and reaching the neural tissue, resulting in minimal
      discomfort and damage to the tissues before the definite shape of the impulse.

      Pre-clinical Data

      A study testing the efficacy of kilohertz and conventional SCS was done on rat models during
      different pain conditions. The findings established that higher frequencies can be delivered
      at lower amplitudes whilst reversing pain behaviours as seen at 50 Hz and at higher intensity
      of motor threshold.

      Moreover, both conventional and kilohertz frequency SCS forms intensity and
      frequency-dependant inhibition of mechanical hypersensitivity, in animal models of
      neuropathic pain. Different intensities (20, 40 and 80% motor threshold) and frequencies (50,
      1kHz and 10kHz) were used. At each frequency, the pulse width was constant. It was observed
      that as frequency was increased, the pulse density also increased.

      Clinical data

      Previous randomised control trials have provided evidence that using frequency ≤1200 Hz and
      pulses ≤ 5% provides efficient relief with HF- SCS.

      A multi-centre trial previously conducted to see the effects of HF-SCS on patients being
      delivered up to 10 kHz of stimulation. Patients were assessed for pain ratings, disability,
      sleep disturbances, and satisfaction, as well as complication rates for up to six months.
      When results were compared to baseline, 88% of patients reported a significant reduction in
      mean back visual analogue scores (VAS) from 8.4 to 2.7 at six months. Seventy four per cent
      of patients reported more than 50% back pain relief at six months. Overall it was concluded
      that individuals in the trial group with chronic back pain, 70% of patients were provided
      with positive improvement and experienced sustained low back and leg pain relief. Substantial
      improvements were also seen for these patients with disability and sleep disturbances.

      If clinically considered, the NRS has substantially reduced in patients who received HF-SCS
      than conventional SCS in patients with neuropathic pain and FBSS. This suggests that HF may
      provide relief in virgin-back patients. Since there remains limited research in this area
      therefore, the main objective of our study is to investigate the response to 1000Hz frequency
      following SCS treatment in "virgin back" patients with intractable lower limb neuropathic
      pain. However based on the PROCO RCT and further WHISPER trial, we aim to establish role of
      microburst and combination therapy in non-responders.

      Our sample size of 30 patients will allow detection of minimal important difference of 2.0 on
      the NRS pain scale at 90% power and alpha of 5%, assuming an outcome standard deviation of
      2.5 and attrition rate at 12-months of 30%. Patient primary and secondary outcomes at each
      follow up point will be compared to baseline values. Data analyses will take account of the
      paired nature of the data and use non-independent t-test for continuous outcomes and
      McNemar's test for binary outcomes.

        -  The primary objective is to investigate the clinical response to high frequency
           (1,000Hz) in patients who are due to have percutaneous spinal cord stimulation for
           intractable lower limb neuropathic pain

        -  The secondary objective will be to investigate the effect on functionality and quality
           of life and adverse events at the high frequency group (1000Hz)
allocation: N/A
intervention model: Single Group Assignment
intervention model description: To investigate the clinical response to high frequency (1,000Hz) in patients who are due to have percutaneous spinal cord stimulation for intractable back and lower limb neuropathic pain
primary purpose: Treatment
masking: None (Open Label)
masking description: Patients will be required to adhere to the study and attend all follow up visits. Informed consent and questionnaires will be administered at visit 0. They will be followed up 4, 12, 24 weeks and 12 months, 24 months after their SCS permanent implant. Questionnaires will be administered at each visit.
measure: Change from baseline numerical Rating Score (NRS) at 4 weeks
time frame: 4 weeks
description: NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.
measure: change from baseline numerical Rating Score (NRS) at 3 months
time frame: 3 months
description: NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.
measure: Change from baseline numerical Rating Score (NRS) at 6 months
time frame: 6 months
description: NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.
measure: Change from baseline numerical Rating Score (NRS) at 12 months
time frame: 12 months
description: NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.
measure: Change from baseline numerical Rating Score (NRS) at 24 months
time frame: 24 months
description: NRS will be used to measure the pain intensity, enabling the patient to express the severity of pain by giving it a numerical value from 0 to 10 on an 11-point numerical pain rating scale. An average overall pain score will be recorded over the last 7 days.
measure: Change from baseline Oswestry Disability Index (ODI) scores at 4 weeks
time frame: 4 weeks
description: A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.
measure: Change from baseline Oswestry Disability Index (ODI) scores at 3 months
time frame: 3 months
description: A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.
measure: Change from baseline Oswestry Disability Index (ODI) scores at 6 months
time frame: 6 months
description: A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.
measure: Change from baseline Oswestry Disability Index (ODI) scores at 12 months
time frame: 12 months
description: A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.
measure: Change from baseline Oswestry Disability Index (ODI) scores at 24 months
time frame: 24 months
description: A commonly used scale for back pain patients with a neuropathic pain component. The test is considered the 'gold standard' of low back functional outcome tools.
measure: Change from baseline Patient's Global Impression of change (PGIC) scores to 4 weeks
time frame: 4 weeks
description: A standard seven point scale would be used to assess the SCS outcome.
measure: Change from baseline Patient's Global Impression of change (PGIC) scores to 3 months
time frame: 3 months
description: A standard seven point scale would be used to assess the SCS outcome.
measure: Change from baseline Patient's Global Impression of change (PGIC) scores to 6 months
time frame: 6 months
description: A standard seven point scale would be used to assess the SCS outcome.
measure: Change from baseline Patient's Global Impression of change (PGIC) scores to 12 months
time frame: 12 months
description: A standard seven point scale would be used to assess the SCS outcome.
measure: Change from baseline Patient's Global Impression of change (PGIC) scores to 24 months
time frame: 24 months
description: A standard seven point scale would be used to assess the SCS outcome.
measure: change from baseline EQ-5D-5L scores at 4 weeks
time frame: 4 weeks
description: The EQ-5D is a standardised instrument used to measure health outcome.
measure: change from baseline EQ-5D-5L scores at 3 months
time frame: 3 months.
description: The EQ-5D is a standardised instrument used to measure health outcome.
measure: change from baseline EQ-5D-5L scores at 6 months
time frame: 6 months.
description: The EQ-5D is a standardised instrument used to measure health outcome.
measure: change from baseline EQ-5D-5L scores at 12 months
time frame: 12 months.
description: The EQ-5D is a standardised instrument used to measure health outcome.
measure: change from baseline EQ-5D-5L scores at 24 months
time frame: 24 months.
description: The EQ-5D is a standardised instrument used to measure health outcome.
measure: Change from baseline Pain and Sleep 3 point index (PSQ-3) at 4 weeks
time frame: 4 weeks
description: The PSQ-3 is an instrument that measures the quality of sleep over a month.
measure: Change from baseline Pain and Sleep 3 point index (PSQ-3) at 3 months
time frame: 3 months
description: The PSQ-3 is an instrument that measures the quality of sleep over a month.
measure: Change from baseline Pain and Sleep 3 point index (PSQ-3) at 6 months
time frame: 6 months
description: The PSQ-3 is an instrument that measures the quality of sleep over a month.
measure: Change from baseline Pain and Sleep 3 point index (PSQ-3) at 12 months
time frame: 12 months
description: The PSQ-3 is an instrument that measures the quality of sleep over a month.
measure: Change from baseline Pain and Sleep 3 point index (PSQ-3) at 24 months
time frame: 24 months
description: The PSQ-3 is an instrument that measures the quality of sleep over a month.
measure: Change from baseline Resource Questionnaire at 12 months
time frame: 12 months.
description: The resource questionnaire measures the impact of health on employment.
measure: Change from baseline Resource Questionnaire at 24 months
time frame: 24 months.
description: The resource questionnaire measures the impact of health on employment.
arm group label: Boston Wavewriter (1000Hz) spinal cord stimulation
arm group type: Experimental
description: To investigate the response to high frequency (1000Hz) in patients who are due to have spinal cord stimulation for neuropathic back pain.
intervention type: Device
intervention name: Boston Wavewriter 1000Hz Spinal cord Stimulation
description: High frequency spinal cord stimulation.
arm group label: Boston Wavewriter (1000Hz) spinal cord stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Kavita Poply, Dr
role: Principal Investigator
affiliation: Barts & The London NHS Trust
last name: Vivek Mehta, Dr
phone: + 44 203 765 8878
email: vivek.mehta@bartshealth.nhs.uk
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Neuralgia
mesh term: Low Back Pain
sharing ipd: No
ipd description: We will follow the policies laid by the local information governance team at Barts Health NHS Trust and NHS code of Confidentiality in accordance to the data protection act.