<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/NCT02982382</url>
  </required_header>
  <id_info>
    <org_study_id>Cvier</org_study_id>
    <secondary_id>U1111-1190-4899</secondary_id>
    <nct_id>NCT02982382</nct_id>
  </id_info>
  <brief_title>Effects of Manipulative Therapy and Pain Education in Individuals With CLBP</brief_title>
  <official_title>Neurophysiological and Functional Effects of Manipulative Therapy and Pain Education in Individuals With Chronic Nonspecific Low Back Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Santa Catarina Federal University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Santa Catarina Federal University</source>
  <brief_summary>
    <textblock>
      The burden of low back pain more than doubled in the last 20 years, probably caused by&#xD;
      biopsychosocial factors. Some noninvasive treatments have been applied in individuals with&#xD;
      chronic nonspecific low back pain as spinal manipulation and pain education. However, it is&#xD;
      not already clear the neurophysiological effects of these treatments.The purpose of this&#xD;
      research is to verify the effects of the technique of spinal manipulation and pain education&#xD;
      in individuals with chronic low back pain&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The outcomes will be subjective pain (measured by Numeric Pain Rating Scale), pressure pain&#xD;
      threshold (measured by Algometer), disability (measured by Roland-Morris Disability&#xD;
      Questionnaire), fear and avoidance beliefs (measured by Fear Avoidance Beliefs&#xD;
      Questionnaire), risk of poor prognosis (measured by STarT Back Screening Tool), quality of&#xD;
      life (measured by Short Form-12v2) and blood biomarkers (measured by ELISA). The data will be&#xD;
      collected by a blinded assessor.&#xD;
&#xD;
      Individuals eligibility is going to be assessed by blinded assessor to determine if they are&#xD;
      or not eligible for this research. Then, they will be informed about the objectives of this&#xD;
      study and asked to sign the consent form. Afterward, the sociodemographic data will be&#xD;
      recorded. The data related to the research outcomes will be collected by the blinded assessor&#xD;
      at baseline assessment, after six weeks and three months.&#xD;
&#xD;
      Random Allocation Before the treatment begins, one of the researchers not involved in the&#xD;
      recruiting and assessment will allocate the individuals in one of the groups. Block&#xD;
      randomization will be used; it is going to generate by randomization.com, this site will&#xD;
      create a list with the randomization sequence, which will be only seen by the physical&#xD;
      therapists that will treat the individuals.&#xD;
&#xD;
      Statistical Methods&#xD;
&#xD;
      Sample size calculation The sample size calculation was calculated with the A-priori test&#xD;
      with the following specifications: Statistical test ANCOVA, the effect size of 0.25, the&#xD;
      statistical power of 80%, and an alpha level of 5%. As a result, the study requires a sample&#xD;
      size of 64 per group or 128 individuals in total.&#xD;
&#xD;
      Analysis of effects of treatment Our research will use the intention-to-treat principles. The&#xD;
      descriptive data and the scores of RMDQ, SBST, FABQ, SF-12v2 and NPRS as well as the pressure&#xD;
      pain threshold means and the values of inflammatory biomarkers, before and after&#xD;
      interventions, will be tabbed on Microsoft Excel 2010. To see the effect of treatment is&#xD;
      going to be used statistical based on intention-to-treat principles, statistical analyses&#xD;
      will be used to analyses data of individuals socio-demographics and clinics characteristics,&#xD;
      and they will be presented by mean and standard deviation. To compare the groups,&#xD;
      Shapiro-Wilk test will be applied to test the normality distribution of data, depending on&#xD;
      this distribution will be used ANOVA one-way for parametric data or Kruskal-Wallis test for&#xD;
      non-parametric data. To compare groups on the pre-intervention period another ANOVA-one way&#xD;
      or another Kruskal-Wallis will be applied.&#xD;
&#xD;
      Covariance analysis (ANCOVA) will be conducted to assess the effect of treatment on the&#xD;
      following outcomes: Scores obtained on RMDQ, FABQ, SF-12v2, SBST and NPRS, pressure pain&#xD;
      threshold and the blood biomarkers concentrations, utilizing the post-treatment means as&#xD;
      dependent variables, the pre-treatment means as co-variables and the group as fixed factor.&#xD;
&#xD;
      To the relationships among the variables must be applied the Pearson correlation coefficient&#xD;
      to parametric data and Spearman correlation coefficient to nonparametric data. To classify&#xD;
      the relationships will be used the Munro's classification, where values between 0.26 and 0.49&#xD;
      will be low, values between 0.50 and 0.69 will be moderate, between 0.70 and 0.89 will be&#xD;
      high values, and between 0.90 and 1.0 will be considered very high. For all of these analyses&#xD;
      will be used the Statistical Package for the Social Sciences (IBM SPSS version 20.0, IBM&#xD;
      Corp, Armonk, New York).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">December 2018</completion_date>
  <primary_completion_date type="Actual">December 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain Intensity</measure>
    <time_frame>6 weeks after randomization</time_frame>
    <description>Numeric Pain Rating Scale (NPRS)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Intensity</measure>
    <time_frame>Baseline, 6 weeks and 3 months</time_frame>
    <description>Numeric Pain Rating Scale (NPRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disabilty</measure>
    <time_frame>baseline, 6 weeks and 3 months</time_frame>
    <description>Rolland Morris Disability Questionnaire (RMDQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure Pain Threshold</measure>
    <time_frame>Baseline, 6 weeks and 3 months</time_frame>
    <description>The pressure pain threshold will be assessed by algometer. It will be realized three times in each point (Five centimeters of the right and left side of the spinal process of L1, L3 and L5, and on the muscle belly of tibialis anterior).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fear and Beliefs about pain</measure>
    <time_frame>Baseline, 6 weeks and 3 months</time_frame>
    <description>Fear Avoidance Belief Questionnaire (FABQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Risk of poor prognosis</measure>
    <time_frame>Baseline, 6 weeks and 3 months</time_frame>
    <description>STarT Back Screening Tool (SBST)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>Baseline, 6 weeks and 3 months</time_frame>
    <description>Short-Form Health Survey 12 version 2 (SF-12v2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Level of Cytokines</measure>
    <time_frame>Baseline, 6 weeks</time_frame>
    <description>Enzyme Linked Immunosorbent Assay (ELISA) to TNF-α, IL-1β, IL-4, IL-6, IL-8, IL-12, IL-10, IL-15, MIP-4, CCL18, MCP-3 / CCL7, MCP-2 / CCL8, IGP - 10 / CXCL10, Stromal Lymphopoietin Receptor (TSLR), Interferon Gamma and CRP.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">128</enrollment>
  <condition>Low Back Pain</condition>
  <arm_group>
    <arm_group_label>Manipulative Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive Manipulative Therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pain Education</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Subjects will receive Pain Education and manual contact over lumbar region</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Manipulative Therapy</intervention_name>
    <description>Subjects will receive techniques of High Velocity and Low Amplitude (HVLA) or grade V manipulation to the lumbar region (lumbar roll), and pain education based on the biopsychosocial approach.</description>
    <arm_group_label>Manipulative Treatment</arm_group_label>
    <other_name>Manual Therapy</other_name>
    <other_name>Grade V Manipulation</other_name>
    <other_name>Spinal Manipulation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pain Education</intervention_name>
    <description>Individuals will receive pain education based in a biopsychosocial approach</description>
    <arm_group_label>Manipulative Treatment</arm_group_label>
    <arm_group_label>Pain Education</arm_group_label>
    <other_name>Neuroscience Pain Education</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sham</intervention_name>
    <description>The individuals will receive a simulation of spinal manipulation (sham) involving manual contact over lumbar region totaling 5 minutes.</description>
    <arm_group_label>Pain Education</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic episodes of nonspecific LBP for at least six months&#xD;
&#xD;
          -  Pain on movement for at least one direction (flexion, extension, side bending or&#xD;
             rotation of the trunk)&#xD;
&#xD;
          -  At least score 3 in NPRS.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1) Previous history of lumbar myelopathy, rheumatic disease, tumors, peripheral or&#xD;
             central neurological disorders&#xD;
&#xD;
          -  2) Historical of trauma, fracture or surgery in lumbar region;&#xD;
&#xD;
          -  3) Nerve root compression signs: important muscle weakness affecting lower limb,&#xD;
             decrease or abolish of patellar and calcaneus reflex and decrease of dermatomes&#xD;
             sensibility of lower limbs.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clécio Vier, PhD Student</last_name>
    <role>Principal Investigator</role>
    <affiliation>Santa Catarina Federal University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Santa Catarina Federal University</name>
      <address>
        <city>Florianopolis</city>
        <state>Santa Catarina</state>
        <zip>88040-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>February 22, 2019</last_update_submitted>
  <last_update_submitted_qc>February 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Santa Catarina Federal University</investigator_affiliation>
    <investigator_full_name>Clecio Vier</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Low Back Pain</keyword>
  <keyword>Musculoskeletal Manipulations</keyword>
  <keyword>Neurophysiology</keyword>
  <keyword>Education</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Back Pain</mesh_term>
    <mesh_term>Low Back Pain</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/NCT02982382
org study id: Cvier
secondary id: U1111-1190-4899
nct id: NCT02982382
lead sponsor: 
The burden of low back pain more than doubled in the last 20 years, probably caused by
      biopsychosocial factors. Some noninvasive treatments have been applied in individuals with
      chronic nonspecific low back pain as spinal manipulation and pain education. However, it is
      not already clear the neurophysiological effects of these treatments.The purpose of this
      research is to verify the effects of the technique of spinal manipulation and pain education
      in individuals with chronic low back pain
The outcomes will be subjective pain (measured by Numeric Pain Rating Scale), pressure pain
      threshold (measured by Algometer), disability (measured by Roland-Morris Disability
      Questionnaire), fear and avoidance beliefs (measured by Fear Avoidance Beliefs
      Questionnaire), risk of poor prognosis (measured by STarT Back Screening Tool), quality of
      life (measured by Short Form-12v2) and blood biomarkers (measured by ELISA). The data will be
      collected by a blinded assessor.

      Individuals eligibility is going to be assessed by blinded assessor to determine if they are
      or not eligible for this research. Then, they will be informed about the objectives of this
      study and asked to sign the consent form. Afterward, the sociodemographic data will be
      recorded. The data related to the research outcomes will be collected by the blinded assessor
      at baseline assessment, after six weeks and three months.

      Random Allocation Before the treatment begins, one of the researchers not involved in the
      recruiting and assessment will allocate the individuals in one of the groups. Block
      randomization will be used; it is going to generate by randomization.com, this site will
      create a list with the randomization sequence, which will be only seen by the physical
      therapists that will treat the individuals.

      Statistical Methods

      Sample size calculation The sample size calculation was calculated with the A-priori test
      with the following specifications: Statistical test ANCOVA, the effect size of 0.25, the
      statistical power of 80%, and an alpha level of 5%. As a result, the study requires a sample
      size of 64 per group or 128 individuals in total.

      Analysis of effects of treatment Our research will use the intention-to-treat principles. The
      descriptive data and the scores of RMDQ, SBST, FABQ, SF-12v2 and NPRS as well as the pressure
      pain threshold means and the values of inflammatory biomarkers, before and after
      interventions, will be tabbed on Microsoft Excel 2010. To see the effect of treatment is
      going to be used statistical based on intention-to-treat principles, statistical analyses
      will be used to analyses data of individuals socio-demographics and clinics characteristics,
      and they will be presented by mean and standard deviation. To compare the groups,
      Shapiro-Wilk test will be applied to test the normality distribution of data, depending on
      this distribution will be used ANOVA one-way for parametric data or Kruskal-Wallis test for
      non-parametric data. To compare groups on the pre-intervention period another ANOVA-one way
      or another Kruskal-Wallis will be applied.

      Covariance analysis (ANCOVA) will be conducted to assess the effect of treatment on the
      following outcomes: Scores obtained on RMDQ, FABQ, SF-12v2, SBST and NPRS, pressure pain
      threshold and the blood biomarkers concentrations, utilizing the post-treatment means as
      dependent variables, the pre-treatment means as co-variables and the group as fixed factor.

      To the relationships among the variables must be applied the Pearson correlation coefficient
      to parametric data and Spearman correlation coefficient to nonparametric data. To classify
      the relationships will be used the Munro's classification, where values between 0.26 and 0.49
      will be low, values between 0.50 and 0.69 will be moderate, between 0.70 and 0.89 will be
      high values, and between 0.90 and 1.0 will be considered very high. For all of these analyses
      will be used the Statistical Package for the Social Sciences (IBM SPSS version 20.0, IBM
      Corp, Armonk, New York).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Pain Intensity
time frame: 6 weeks after randomization
description: Numeric Pain Rating Scale (NPRS)
measure: Pain Intensity
time frame: Baseline, 6 weeks and 3 months
description: Numeric Pain Rating Scale (NPRS)
measure: Disabilty
time frame: baseline, 6 weeks and 3 months
description: Rolland Morris Disability Questionnaire (RMDQ)
measure: Pressure Pain Threshold
time frame: Baseline, 6 weeks and 3 months
description: The pressure pain threshold will be assessed by algometer. It will be realized three times in each point (Five centimeters of the right and left side of the spinal process of L1, L3 and L5, and on the muscle belly of tibialis anterior).
measure: Fear and Beliefs about pain
time frame: Baseline, 6 weeks and 3 months
description: Fear Avoidance Belief Questionnaire (FABQ)
measure: Risk of poor prognosis
time frame: Baseline, 6 weeks and 3 months
description: STarT Back Screening Tool (SBST)
measure: Quality of Life
time frame: Baseline, 6 weeks and 3 months
description: Short-Form Health Survey 12 version 2 (SF-12v2)
measure: Serum Level of Cytokines
time frame: Baseline, 6 weeks
description: Enzyme Linked Immunosorbent Assay (ELISA) to TNF-α, IL-1β, IL-4, IL-6, IL-8, IL-12, IL-10, IL-15, MIP-4, CCL18, MCP-3 / CCL7, MCP-2 / CCL8, IGP - 10 / CXCL10, Stromal Lymphopoietin Receptor (TSLR), Interferon Gamma and CRP.
arm group label: Manipulative Treatment
arm group type: Experimental
description: Subjects will receive Manipulative Therapy
arm group label: Pain Education
arm group type: Sham Comparator
description: Subjects will receive Pain Education and manual contact over lumbar region
intervention type: Other
intervention name: Manipulative Therapy
description: Subjects will receive techniques of High Velocity and Low Amplitude (HVLA) or grade V manipulation to the lumbar region (lumbar roll), and pain education based on the biopsychosocial approach.
arm group label: Manipulative Treatment
other name: Manual Therapy
other name: Grade V Manipulation
other name: Spinal Manipulation
intervention type: Other
intervention name: Pain Education
description: Individuals will receive pain education based in a biopsychosocial approach
arm group label: Manipulative Treatment
arm group label: Pain Education
other name: Neuroscience Pain Education
intervention type: Other
intervention name: Sham
description: The individuals will receive a simulation of spinal manipulation (sham) involving manual contact over lumbar region totaling 5 minutes.
arm group label: Pain Education
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Clécio Vier, PhD Student
role: Principal Investigator
affiliation: Santa Catarina Federal University
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Santa Catarina Federal University
investigator full name: Clecio Vier
investigator title: Principal Investigator
mesh term: Back Pain
mesh term: Low Back Pain