<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/NCT03753711</url>
  </required_header>
  <id_info>
    <org_study_id>LDH-UH</org_study_id>
    <nct_id>NCT03753711</nct_id>
  </id_info>
  <brief_title>Paraspinal Muscle Remodeling</brief_title>
  <official_title>Paraspinal Muscle Remodeling in Patients With Unilateral Lumbar Disc Herniation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hasselt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ziekenhuis Oost-Limburg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jessa Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hasselt University</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>
      Lumbar disc herniation is the most common diagnosed degenerative pathology in the lumbar&#xD;
      spine with a prevalence of 2 to 3% in the adult population. Unilateral lumbar disc herniation&#xD;
      is characterized by compression or irritation of the lumbar nerve roots or dural sac by&#xD;
      either protrusion, extrusion or sequestration of the nucleus pulposus, mostly in the&#xD;
      posterolateral region. Compression or irritation of the lumbar nerve roots and dural sac can&#xD;
      induce unilateral sensory and motor symptoms. Therefore, it is the principal cause of lumbar&#xD;
      spinal surgery.&#xD;
&#xD;
      Different imaging studies have investigated asymmetry of the paraspinal muscles in patient&#xD;
      with unilateral low back pain due to lumbar discus herniation. Both animal and human studies&#xD;
      indicate a reduction in total muscle cross-sectional area, increased fat infiltration and&#xD;
      fibrosis within the lumbar multifidus at the affected side.&#xD;
&#xD;
      Increased fat infiltration is clinically important because there is a correlation between the&#xD;
      amount of intramuscular fat and lumbar muscle dysfunction. Not only fat infiltration&#xD;
      correlates with lumbar dysfunction, also a lower multifidus cross-sectional area is&#xD;
      associated with and predictive for low back pain. This indicates that there is an association&#xD;
      between paraspinal muscle changes/ remodeling and muscle dysfunction that could lead to low&#xD;
      back pain.&#xD;
&#xD;
      The aim of this research is to quantify the decrease in muscle and muscle fibre size, the&#xD;
      amount of fat infiltration, and the amount of fibrosis present within the multifidus muscle&#xD;
      at the herniated side in relation to the unaffected side. The second aim is to investigate&#xD;
      the possible role of different cell types in the process of muscle remodeling. The last aim&#xD;
      of this study is to correlate these muscular changes with long-term functional outcomes such&#xD;
      as pain, fear and disability. This information can possibly contribute to the etiology of&#xD;
      paraspinal muscle changes, and provide a handgrip to future research.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Actual">August 31, 2021</completion_date>
  <primary_completion_date type="Actual">August 31, 2021</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>muscle biopsy sample (musculus multifidus)</measure>
    <time_frame>day 1</time_frame>
    <description>Histochemical analyses: Masson's trichrome and haematoxylin and eosin staining will be used to visualize connective and adipose tissues within a muscle cross-section.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>muscle biopsy sample (musculus multifidus)</measure>
    <time_frame>day 1</time_frame>
    <description>Immunofluorescent analyses: Primary and secondary immunofluorescent antibody's against MHC I, IIA and IIX, laminin, satellite cells / muscle stem cells (PAX-7, MyoD, Myogenin), fibro-adipogenic cells/ mesenchymal progenitor cells (PDGFR-alfa) and myonuclei (DAPI) will be used.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>muscle biopsy sample (musculus multifidus)</measure>
    <time_frame>day 1</time_frame>
    <description>Real-time PCR: Inflammatory markers and growth factors will be measured using real-time polymerase chain reaction.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MRI</measure>
    <time_frame>day 1</time_frame>
    <description>Medical imaging: Pre-operative MRI images will be requested from the department of radiology to measure total muscle cross-sectional area and intramuscular fat infiltration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Numeric Pain Rating Score (NPRS)</measure>
    <time_frame>day 1</time_frame>
    <description>this is a tool to provide an indication of the amount of pain a participant is feeling. It's a scale with 11 scores (0-10). It's a scale in which score 0 means 'no pain' and score 10 means 'the highest imaginable pain'. An improvement of 2 levels is considered clinically relevant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numeric Pain Rating Score (NPRS)</measure>
    <time_frame>week 6</time_frame>
    <description>this is a tool to provide an indication of the amount of pain a participant is feeling. It's a scale with 11 scores (0-10). It's a scale in which score 0 means 'no pain' and score 10 means 'the highest imaginable pain'. An improvement of 2 levels is considered clinically relevant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numeric Pain Rating Score (NPRS)</measure>
    <time_frame>month 6</time_frame>
    <description>this is a tool to provide an indication of the amount of pain a participant is feeling. It's a scale with 11 scores (0-10). It's a scale in which score 0 means 'no pain' and score 10 means 'the highest imaginable pain'. An improvement of 2 levels is considered clinically relevant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Oswestry Disability Index (ODI)</measure>
    <time_frame>day1</time_frame>
    <description>this is a questionnaire than has been proven valid and reliable to evaluate the restrictions that people with low back pain experience during their daily living. It consist of 10 items that will be scored on a 5 point scale. Using the total score you can calculate a percentage restriction degree. The score is calculated using the sum of the scores (0-5) from all 10 questions and multiply them times two. The final score is interpreted as following: 0-20%: minimal disability, 21-40%: moderate disability, 41-60%: severe disability, 61-80%: crippled, 81-100% bed bound.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Oswestry Disability Index (ODI)</measure>
    <time_frame>week 6</time_frame>
    <description>this is a questionnaire than has been proven valid and reliable to evaluate the restrictions that people with low back pain experience during their daily living. It consist of 10 items that will be scored on a 5 point scale. Using the total score you can calculate a percentage restriction degree. The score is calculated using the sum of the scores (0-5) from all 10 questions and multiply them times two. The final score is interpreted as following: 0-20%: minimal disability, 21-40%: moderate disability, 41-60%: severe disability, 61-80%: crippled, 81-100% bed bound.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Oswestry Disability Index (ODI)</measure>
    <time_frame>month 6</time_frame>
    <description>this is a questionnaire than has been proven valid and reliable to evaluate the restrictions that people with low back pain experience during their daily living. It consist of 10 items that will be scored on a 5 point scale. Using the total score you can calculate a percentage restriction degree. The score is calculated using the sum of the scores (0-5) from all 10 questions and multiply them times two. The final score is interpreted as following: 0-20%: minimal disability, 21-40%: moderate disability, 41-60%: severe disability, 61-80%: crippled, 81-100% bed bound.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tampa Scale for Kinesiophobia (TSK)</measure>
    <time_frame>day 1</time_frame>
    <description>this is an ordinal 17 item questionnaire that inventories pain-related fear of movement for persons with subacute and chronic low back pain or fibromyalgia. A higher score relates to more pain-related fear. A score &gt;37/68 (with 68 being the highest possible score) means there is fear of movement present.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tampa Scale for Kinesiophobia (TSK)</measure>
    <time_frame>week 6</time_frame>
    <description>this is an ordinal 17 item questionnaire that inventories pain-related fear of movement for persons with subacute and chronic low back pain or fibromyalgia. A higher score relates to more pain-related fear. A score &gt;37/68 (with 68 being the highest possible score) means there is fear of movement present.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tampa Scale for Kinesiophobia (TSK)</measure>
    <time_frame>month 6</time_frame>
    <description>this is an ordinal 17 item questionnaire that inventories pain-related fear of movement for persons with subacute and chronic low back pain or fibromyalgia. A higher score relates to more pain-related fear. A score &gt;37/68 (with 68 being the highest possible score) means there is fear of movement present.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Lumbar Disc Herniation</condition>
  <arm_group>
    <arm_group_label>LDH (lumbar disc hernia)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Multifidus muscle biopsy during minimally invasive back surgery</intervention_name>
    <description>Bilateral biopsy of the multifidus muscle in patient with a unilateral disc hernia.</description>
    <arm_group_label>LDH (lumbar disc hernia)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Unilateral lumbar disc hernia (diagnosed using MRI)&#xD;
&#xD;
          -  Age between 18-55&#xD;
&#xD;
          -  Understanding the Dutch language&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Spinal surgery within the last year&#xD;
&#xD;
          -  Degenerative or other spinal pathology (except disc hernia)&#xD;
&#xD;
          -  Contraindications to undergo a MRI&#xD;
&#xD;
          -  Other known pathologies that might affect muscle biology/ morphology&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frank Vandenabeele, prof. dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hasselt University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sjoerd Stevens, drs.</last_name>
    <role>Study Chair</role>
    <affiliation>Hasselt University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jessa Ziekenhuis</name>
      <address>
        <city>Hasselt</city>
        <zip>3500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>May 18, 2022</last_update_submitted>
  <last_update_submitted_qc>May 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hasselt University</investigator_affiliation>
    <investigator_full_name>Frank Vandenabeele</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>lumbar disc herniation</keyword>
  <keyword>hernia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intervertebral Disc Displacement</mesh_term>
    <mesh_term>Hernia</mesh_term>
  </condition_browse>
  <!-- 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/NCT03753711
org study id: LDH-UH
nct id: NCT03753711
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Lumbar disc herniation is the most common diagnosed degenerative pathology in the lumbar
      spine with a prevalence of 2 to 3% in the adult population. Unilateral lumbar disc herniation
      is characterized by compression or irritation of the lumbar nerve roots or dural sac by
      either protrusion, extrusion or sequestration of the nucleus pulposus, mostly in the
      posterolateral region. Compression or irritation of the lumbar nerve roots and dural sac can
      induce unilateral sensory and motor symptoms. Therefore, it is the principal cause of lumbar
      spinal surgery.

      Different imaging studies have investigated asymmetry of the paraspinal muscles in patient
      with unilateral low back pain due to lumbar discus herniation. Both animal and human studies
      indicate a reduction in total muscle cross-sectional area, increased fat infiltration and
      fibrosis within the lumbar multifidus at the affected side.

      Increased fat infiltration is clinically important because there is a correlation between the
      amount of intramuscular fat and lumbar muscle dysfunction. Not only fat infiltration
      correlates with lumbar dysfunction, also a lower multifidus cross-sectional area is
      associated with and predictive for low back pain. This indicates that there is an association
      between paraspinal muscle changes/ remodeling and muscle dysfunction that could lead to low
      back pain.

      The aim of this research is to quantify the decrease in muscle and muscle fibre size, the
      amount of fat infiltration, and the amount of fibrosis present within the multifidus muscle
      at the herniated side in relation to the unaffected side. The second aim is to investigate
      the possible role of different cell types in the process of muscle remodeling. The last aim
      of this study is to correlate these muscular changes with long-term functional outcomes such
      as pain, fear and disability. This information can possibly contribute to the etiology of
      paraspinal muscle changes, and provide a handgrip to future research.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: muscle biopsy sample (musculus multifidus)
time frame: day 1
description: Histochemical analyses: Masson's trichrome and haematoxylin and eosin staining will be used to visualize connective and adipose tissues within a muscle cross-section.
measure: muscle biopsy sample (musculus multifidus)
time frame: day 1
description: Immunofluorescent analyses: Primary and secondary immunofluorescent antibody's against MHC I, IIA and IIX, laminin, satellite cells / muscle stem cells (PAX-7, MyoD, Myogenin), fibro-adipogenic cells/ mesenchymal progenitor cells (PDGFR-alfa) and myonuclei (DAPI) will be used.
measure: muscle biopsy sample (musculus multifidus)
time frame: day 1
description: Real-time PCR: Inflammatory markers and growth factors will be measured using real-time polymerase chain reaction.
measure: MRI
time frame: day 1
description: Medical imaging: Pre-operative MRI images will be requested from the department of radiology to measure total muscle cross-sectional area and intramuscular fat infiltration.
measure: Numeric Pain Rating Score (NPRS)
time frame: day 1
description: this is a tool to provide an indication of the amount of pain a participant is feeling. It's a scale with 11 scores (0-10). It's a scale in which score 0 means 'no pain' and score 10 means 'the highest imaginable pain'. An improvement of 2 levels is considered clinically relevant.
measure: Numeric Pain Rating Score (NPRS)
time frame: week 6
description: this is a tool to provide an indication of the amount of pain a participant is feeling. It's a scale with 11 scores (0-10). It's a scale in which score 0 means 'no pain' and score 10 means 'the highest imaginable pain'. An improvement of 2 levels is considered clinically relevant.
measure: Numeric Pain Rating Score (NPRS)
time frame: month 6
description: this is a tool to provide an indication of the amount of pain a participant is feeling. It's a scale with 11 scores (0-10). It's a scale in which score 0 means 'no pain' and score 10 means 'the highest imaginable pain'. An improvement of 2 levels is considered clinically relevant.
measure: Modified Oswestry Disability Index (ODI)
time frame: day1
description: this is a questionnaire than has been proven valid and reliable to evaluate the restrictions that people with low back pain experience during their daily living. It consist of 10 items that will be scored on a 5 point scale. Using the total score you can calculate a percentage restriction degree. The score is calculated using the sum of the scores (0-5) from all 10 questions and multiply them times two. The final score is interpreted as following: 0-20%: minimal disability, 21-40%: moderate disability, 41-60%: severe disability, 61-80%: crippled, 81-100% bed bound.
measure: Modified Oswestry Disability Index (ODI)
time frame: week 6
description: this is a questionnaire than has been proven valid and reliable to evaluate the restrictions that people with low back pain experience during their daily living. It consist of 10 items that will be scored on a 5 point scale. Using the total score you can calculate a percentage restriction degree. The score is calculated using the sum of the scores (0-5) from all 10 questions and multiply them times two. The final score is interpreted as following: 0-20%: minimal disability, 21-40%: moderate disability, 41-60%: severe disability, 61-80%: crippled, 81-100% bed bound.
measure: Modified Oswestry Disability Index (ODI)
time frame: month 6
description: this is a questionnaire than has been proven valid and reliable to evaluate the restrictions that people with low back pain experience during their daily living. It consist of 10 items that will be scored on a 5 point scale. Using the total score you can calculate a percentage restriction degree. The score is calculated using the sum of the scores (0-5) from all 10 questions and multiply them times two. The final score is interpreted as following: 0-20%: minimal disability, 21-40%: moderate disability, 41-60%: severe disability, 61-80%: crippled, 81-100% bed bound.
measure: Tampa Scale for Kinesiophobia (TSK)
time frame: day 1
description: this is an ordinal 17 item questionnaire that inventories pain-related fear of movement for persons with subacute and chronic low back pain or fibromyalgia. A higher score relates to more pain-related fear. A score >37/68 (with 68 being the highest possible score) means there is fear of movement present.
measure: Tampa Scale for Kinesiophobia (TSK)
time frame: week 6
description: this is an ordinal 17 item questionnaire that inventories pain-related fear of movement for persons with subacute and chronic low back pain or fibromyalgia. A higher score relates to more pain-related fear. A score >37/68 (with 68 being the highest possible score) means there is fear of movement present.
measure: Tampa Scale for Kinesiophobia (TSK)
time frame: month 6
description: this is an ordinal 17 item questionnaire that inventories pain-related fear of movement for persons with subacute and chronic low back pain or fibromyalgia. A higher score relates to more pain-related fear. A score >37/68 (with 68 being the highest possible score) means there is fear of movement present.
arm group label: LDH (lumbar disc hernia)
arm group type: Experimental
intervention type: Procedure
intervention name: Multifidus muscle biopsy during minimally invasive back surgery
description: Bilateral biopsy of the multifidus muscle in patient with a unilateral disc hernia.
arm group label: LDH (lumbar disc hernia)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Frank Vandenabeele, prof. dr.
role: Principal Investigator
affiliation: Hasselt University
last name: Sjoerd Stevens, drs.
role: Study Chair
affiliation: Hasselt University
facility: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: Hasselt University
investigator full name: Frank Vandenabeele
investigator title: Principal Investigator
mesh term: Intervertebral Disc Displacement
mesh term: Hernia