<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/NCT03228160</url>
  </required_header>
  <id_info>
    <org_study_id>N201511030</org_study_id>
    <nct_id>NCT03228160</nct_id>
  </id_info>
  <brief_title>Light Irradiation and Outcome for Neuropathic Pain</brief_title>
  <official_title>Effects of Linearly Polarized Near-Infrared Irradiation in Patients With Sympathetically Maintained Neuropathic Pain Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taipei Medical University Shuang Ho Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Taipei Medical University Shuang Ho Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background. Sympathetically maintained pain (SMP) can be effectively relieved by light&#xD;
      irradiation to the area near stellate ganglion (SGI), which is applied as an alternative to&#xD;
      sympathetic blockade. The clinical efficiency of SGI on heart rate variability (HRV) and its&#xD;
      association with pain outcome need to be further identified.&#xD;
&#xD;
      Objectives. This study is aimed to identify the effects of SGI on pain, HRV indices, quality&#xD;
      of life, and function outcomes.&#xD;
&#xD;
      Design. A prospective, double blind, randomized designed study Setting. An outpatient pain&#xD;
      medicine clinic Subjects and Methods. A total of 44 patients will be enrolled and randomized&#xD;
      to their allocations: the experimental group (EG, n=22) and control group (CG, n=22). All&#xD;
      patients in EG will receive 12 sessions (twice a week) of standard SGI, while those in CG go&#xD;
      through the same protocol except a shame irradiation is applied. Pain, HRV variables, quality&#xD;
      of life, and function outcoms are measured before and after SGI in each session. All measures&#xD;
      at the first-half and second-half courses are analyzed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sympathetically maintained pain (SMP) is defined as an aspect of pain which is maintained or&#xD;
      mediated by sympathetic efferent activity including the action of circulating catecholamine&#xD;
      and is often linked to the complex regional pain syndrome (CRPS). SMP has been categorized as&#xD;
      a subset of neuropathic pain mediated by the underlying mechanism of peripheral sensitization&#xD;
      referring to noradrenergic sensitization of peripheral afferent nociceptive fibers and a&#xD;
      pathologically sympathetic-sensory coupling interaction between the efferent sympathetic and&#xD;
      the afferent system. Besides, SMP is associated with vasomotor and sudomotor dysfunction&#xD;
      through either peripheral integerized by an adrenoreceptor stimulated or central organized by&#xD;
      sensitization. Therefore, modulation of sympathetic activity either by means of&#xD;
      pharmacological analgesics or local sympathetic ganglion blockade may influence the pain&#xD;
      course in patients with chronic pain and hyperalgesia that were suspected to be&#xD;
      sympathetically maintained.&#xD;
&#xD;
      The pain associated with sympathetic activity can be relieved by blockage of efferent&#xD;
      sympathetic nerves to the affected area. Stellate ganglion block (SGB), a local anesthetic&#xD;
      blockade of sympathetic ganglia, has been advocated as an early intervention to achieve&#xD;
      sympatholysis and its strong evidence had been identified. However, a success of SGB depends&#xD;
      on the skilled invasive technique in application and several potential complications may be&#xD;
      elucidated. Alternatively, the light irradiation near the stellate ganglion region (SGI)&#xD;
      using either low-reactive level laser or linear-polarized near-infrared light irradiation had&#xD;
      been used as a noninvasive method for local anesthetic sympathetic blockade. Furthermore, SGI&#xD;
      can be safely and conveniently performed in clinical practice even when an anesthetic&#xD;
      physician is not available, had been well tolerated by patients, and no thermal injury or&#xD;
      side effects were reported by literatures.&#xD;
&#xD;
      SGI had been identified to offer similar effects of SGB for patients with neuropathic pain,&#xD;
      including improving blood flow by dilating vessels and reducing pain by directly blocking&#xD;
      afferent nociceptive signal traveling via sympathetic pathways. The irradiation effect on&#xD;
      heart rate variability (HRV), which is an objectively non-invasive marker of the autonomic&#xD;
      nervous system, had not yet been well established. If the pathogenesis of SMP is closely&#xD;
      referred to some abnormality in the function of autonomic nerve system (ANS), it is more&#xD;
      necessary to measure autonomic activity for validation rather than pain status, local&#xD;
      temperature or peripheral blood flow. Whether the relieved pain level after SGI is associated&#xD;
      to HRV changes remains unclear. Identifying the relationship between HRV and pain status&#xD;
      following SGI allows the clinicians to set a prompt protocol of phototherapy using SGI, and&#xD;
      to accurately follow the outcome of autonomic dysfunction in patients with SMP.&#xD;
&#xD;
      The purpose of this study was to demonstrate the sympatholytic and clinical effects of linear&#xD;
      polarized near-infrared irradiation applied on stellate ganglion in patients with SMP.&#xD;
&#xD;
      An experimental design with two groups will be used and a double blind, prospective&#xD;
      randomized control trial will be conducted at the chronic pain medicine center in the&#xD;
      physical medicine and rehabilitation department. Potential patients will be recruited. The&#xD;
      enrolled patients will be randomly assigned to the experimental group or the control group&#xD;
      (CG) using a table of random numbers. Patients in the experimental group will receive a&#xD;
      6-week standard SGI treatment protocol (12 irradiation sessions), while those in the control&#xD;
      group being undergo a sham irradiation during the same period. Both the investigators and the&#xD;
      patients will be blinded to the group assignments. All outcome measures will be collected by&#xD;
      a trained research assistant at the baseline admission prior to SGI therapy, before and after&#xD;
      SGI at each irradiation session, and at the follow up admission immediately after the end of&#xD;
      6-week treatment period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 1, 2016</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2022</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>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visual analogue scale (VAS: 0-100mm)</measure>
    <time_frame>Baseline</time_frame>
    <description>A visual analogue scale (VAS: 0-100mm) representing pain intensity, where 0 represented no pain and 100 indicated unbearable pain. Participants are instructed to indicate a point on the scale corresponding to the pain intensity. The distance from the left end to the selected point is measured to calculate the pain score in millimeters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visual analogue scale (VAS: 0-100mm)</measure>
    <time_frame>Follow up at 3 months (end of intervention)</time_frame>
    <description>A visual analogue scale (VAS: 0-100mm) representing pain intensity, where 0 represented no pain and 100 indicated unbearable pain. Participants are instructed to indicate a point on the scale corresponding to the pain intensity. The distance from the left end to the selected point is measured to calculate the pain score in millimeters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Short Form (36) Health Surve (SF-36)</measure>
    <time_frame>Baseline, follow up at 3 months after end of intervention</time_frame>
    <description>Assessment of quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short Form (36) Health Surve (SF-36)</measure>
    <time_frame>Follow up at 3 months after end of intervention</time_frame>
    <description>Assessment of quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disability of the Arm, Shoulder and Hand (DASH)</measure>
    <time_frame>Baseline, follow up at 3 months after end of intervention</time_frame>
    <description>Function evaluation of upper quarter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disability of the Arm, Shoulder and Hand (DASH)</measure>
    <time_frame>Follow up at 3 months after end of intervention</time_frame>
    <description>Function evaluation of upper quarter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate variability (HRV) analysis</measure>
    <time_frame>Baseline, follow up at 3 months after end of intervention</time_frame>
    <description>HRV was measured using an ANSWatch wrist monitor (Taiwan Scientific Co., Taipei, Taiwan).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate variability (HRV) analysis</measure>
    <time_frame>Follow up at 3 months after end of intervention</time_frame>
    <description>HRV was measured using an ANSWatch wrist monitor (Taiwan Scientific Co., Taipei, Taiwan).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Complex Regional Pain Syndrome</condition>
  <arm_group>
    <arm_group_label>SGI irradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental group with active Linearly Polarized Near-Infrared light irradiation to stellate ganglion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Shame irradiation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Control group with shame Linearly Polarized Near-Infrared light irradiation to stellate ganglion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Linearly Polarized Near-Infrared light Irradiation</intervention_name>
    <description>The SGI was carried out with the use of a linear-polarized near-infrared irradiation device, Minato Alphabeam Infrared Ray Therapy Unit (Minato Medical Science Co., Ltd., Hyogo, Japan), by a senior physical therapist. The maximum output was 3000 mW/cm² at wavelengths of 0.7 to 1.6 m-⁶, including a combination of red and near-infrared radiation. All patients in the experimental group received SGI under the conditions as follows: output, 90%; irradiation circle 1:2 (irradiation 3 seconds followed by 7-seconds pause); duration of irradiation, 10 min; and total irradiation energy density, 194.8 J/cm². The instrument in the control group with shame irradiation was the same as that in the experimental group with the exception that emitted radiation from device was inactive.</description>
    <arm_group_label>SGI irradiation</arm_group_label>
    <arm_group_label>Shame irradiation</arm_group_label>
    <other_name>Phototherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who age from 20 to 80 years and have a diagnosis of neuropathetic pain will&#xD;
             be recruited from the chronic pain center at our hospital.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who meted the following criteria are excluded:&#xD;
&#xD;
               1. Diagnosis of glioblastoma,&#xD;
&#xD;
               2. History of heart disease, serious arrhythmia or pacemaker user,&#xD;
&#xD;
               3. Simmond disease or postpartum hypopituitarism,&#xD;
&#xD;
               4. Habitual smoking or consumption of stimulant beverages such as tea, coffee, or&#xD;
                  alcohol, and&#xD;
&#xD;
               5. Any other condition that is unsuitable for phototherapy by a doctor's evaluation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shuang Ho Hospital, Taipei Medical University</name>
      <address>
        <city>New Taipei City</city>
        <zip>23561</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>January 29, 2016</study_first_submitted>
  <study_first_submitted_qc>July 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Taipei Medical University Shuang Ho Hospital</investigator_affiliation>
    <investigator_full_name>Chun-De Liao, PT</investigator_full_name>
    <investigator_title>Physical therapist</investigator_title>
  </responsible_party>
  <keyword>Sympathetically Maintained Pain</keyword>
  <keyword>Linear-Polarized Near-Infrared Irradiation</keyword>
  <keyword>Stellate Ganglion</keyword>
  <keyword>Heart Rate Variability</keyword>
  <keyword>Autonomic Dysfunction Outcome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
    <mesh_term>Complex Regional Pain Syndromes</mesh_term>
    <mesh_term>Reflex Sympathetic Dystrophy</mesh_term>
    <mesh_term>Syndrome</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/NCT03228160
org study id: N201511030
nct id: NCT03228160
lead sponsor: 
has dmc: No
Background. Sympathetically maintained pain (SMP) can be effectively relieved by light
      irradiation to the area near stellate ganglion (SGI), which is applied as an alternative to
      sympathetic blockade. The clinical efficiency of SGI on heart rate variability (HRV) and its
      association with pain outcome need to be further identified.

      Objectives. This study is aimed to identify the effects of SGI on pain, HRV indices, quality
      of life, and function outcomes.

      Design. A prospective, double blind, randomized designed study Setting. An outpatient pain
      medicine clinic Subjects and Methods. A total of 44 patients will be enrolled and randomized
      to their allocations: the experimental group (EG, n=22) and control group (CG, n=22). All
      patients in EG will receive 12 sessions (twice a week) of standard SGI, while those in CG go
      through the same protocol except a shame irradiation is applied. Pain, HRV variables, quality
      of life, and function outcoms are measured before and after SGI in each session. All measures
      at the first-half and second-half courses are analyzed.
Sympathetically maintained pain (SMP) is defined as an aspect of pain which is maintained or
      mediated by sympathetic efferent activity including the action of circulating catecholamine
      and is often linked to the complex regional pain syndrome (CRPS). SMP has been categorized as
      a subset of neuropathic pain mediated by the underlying mechanism of peripheral sensitization
      referring to noradrenergic sensitization of peripheral afferent nociceptive fibers and a
      pathologically sympathetic-sensory coupling interaction between the efferent sympathetic and
      the afferent system. Besides, SMP is associated with vasomotor and sudomotor dysfunction
      through either peripheral integerized by an adrenoreceptor stimulated or central organized by
      sensitization. Therefore, modulation of sympathetic activity either by means of
      pharmacological analgesics or local sympathetic ganglion blockade may influence the pain
      course in patients with chronic pain and hyperalgesia that were suspected to be
      sympathetically maintained.

      The pain associated with sympathetic activity can be relieved by blockage of efferent
      sympathetic nerves to the affected area. Stellate ganglion block (SGB), a local anesthetic
      blockade of sympathetic ganglia, has been advocated as an early intervention to achieve
      sympatholysis and its strong evidence had been identified. However, a success of SGB depends
      on the skilled invasive technique in application and several potential complications may be
      elucidated. Alternatively, the light irradiation near the stellate ganglion region (SGI)
      using either low-reactive level laser or linear-polarized near-infrared light irradiation had
      been used as a noninvasive method for local anesthetic sympathetic blockade. Furthermore, SGI
      can be safely and conveniently performed in clinical practice even when an anesthetic
      physician is not available, had been well tolerated by patients, and no thermal injury or
      side effects were reported by literatures.

      SGI had been identified to offer similar effects of SGB for patients with neuropathic pain,
      including improving blood flow by dilating vessels and reducing pain by directly blocking
      afferent nociceptive signal traveling via sympathetic pathways. The irradiation effect on
      heart rate variability (HRV), which is an objectively non-invasive marker of the autonomic
      nervous system, had not yet been well established. If the pathogenesis of SMP is closely
      referred to some abnormality in the function of autonomic nerve system (ANS), it is more
      necessary to measure autonomic activity for validation rather than pain status, local
      temperature or peripheral blood flow. Whether the relieved pain level after SGI is associated
      to HRV changes remains unclear. Identifying the relationship between HRV and pain status
      following SGI allows the clinicians to set a prompt protocol of phototherapy using SGI, and
      to accurately follow the outcome of autonomic dysfunction in patients with SMP.

      The purpose of this study was to demonstrate the sympatholytic and clinical effects of linear
      polarized near-infrared irradiation applied on stellate ganglion in patients with SMP.

      An experimental design with two groups will be used and a double blind, prospective
      randomized control trial will be conducted at the chronic pain medicine center in the
      physical medicine and rehabilitation department. Potential patients will be recruited. The
      enrolled patients will be randomly assigned to the experimental group or the control group
      (CG) using a table of random numbers. Patients in the experimental group will receive a
      6-week standard SGI treatment protocol (12 irradiation sessions), while those in the control
      group being undergo a sham irradiation during the same period. Both the investigators and the
      patients will be blinded to the group assignments. All outcome measures will be collected by
      a trained research assistant at the baseline admission prior to SGI therapy, before and after
      SGI at each irradiation session, and at the follow up admission immediately after the end of
      6-week treatment period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Visual analogue scale (VAS: 0-100mm)
time frame: Baseline
description: A visual analogue scale (VAS: 0-100mm) representing pain intensity, where 0 represented no pain and 100 indicated unbearable pain. Participants are instructed to indicate a point on the scale corresponding to the pain intensity. The distance from the left end to the selected point is measured to calculate the pain score in millimeters.
measure: Visual analogue scale (VAS: 0-100mm)
time frame: Follow up at 3 months (end of intervention)
description: A visual analogue scale (VAS: 0-100mm) representing pain intensity, where 0 represented no pain and 100 indicated unbearable pain. Participants are instructed to indicate a point on the scale corresponding to the pain intensity. The distance from the left end to the selected point is measured to calculate the pain score in millimeters.
measure: Short Form (36) Health Surve (SF-36)
time frame: Baseline, follow up at 3 months after end of intervention
description: Assessment of quality of life
measure: Short Form (36) Health Surve (SF-36)
time frame: Follow up at 3 months after end of intervention
description: Assessment of quality of life
measure: Disability of the Arm, Shoulder and Hand (DASH)
time frame: Baseline, follow up at 3 months after end of intervention
description: Function evaluation of upper quarter
measure: Disability of the Arm, Shoulder and Hand (DASH)
time frame: Follow up at 3 months after end of intervention
description: Function evaluation of upper quarter
measure: Heart rate variability (HRV) analysis
time frame: Baseline, follow up at 3 months after end of intervention
description: HRV was measured using an ANSWatch wrist monitor (Taiwan Scientific Co., Taipei, Taiwan).
measure: Heart rate variability (HRV) analysis
time frame: Follow up at 3 months after end of intervention
description: HRV was measured using an ANSWatch wrist monitor (Taiwan Scientific Co., Taipei, Taiwan).
arm group label: SGI irradiation
arm group type: Experimental
description: Experimental group with active Linearly Polarized Near-Infrared light irradiation to stellate ganglion.
arm group label: Shame irradiation
arm group type: Sham Comparator
description: Control group with shame Linearly Polarized Near-Infrared light irradiation to stellate ganglion.
intervention type: Other
intervention name: Linearly Polarized Near-Infrared light Irradiation
description: The SGI was carried out with the use of a linear-polarized near-infrared irradiation device, Minato Alphabeam Infrared Ray Therapy Unit (Minato Medical Science Co., Ltd., Hyogo, Japan), by a senior physical therapist. The maximum output was 3000 mW/cm² at wavelengths of 0.7 to 1.6 m-⁶, including a combination of red and near-infrared radiation. All patients in the experimental group received SGI under the conditions as follows: output, 90%; irradiation circle 1:2 (irradiation 3 seconds followed by 7-seconds pause); duration of irradiation, 10 min; and total irradiation energy density, 194.8 J/cm². The instrument in the control group with shame irradiation was the same as that in the experimental group with the exception that emitted radiation from device was inactive.
arm group label: SGI irradiation
arm group label: Shame irradiation
other name: Phototherapy
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Taipei Medical University Shuang Ho Hospital
investigator full name: Chun-De Liao, PT
investigator title: Physical therapist
mesh term: Neuralgia
mesh term: Complex Regional Pain Syndromes
mesh term: Reflex Sympathetic Dystrophy
mesh term: Syndrome
sharing ipd: No