<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/NCT01670292</url>
  </required_header>
  <id_info>
    <org_study_id>PRiSM Study</org_study_id>
    <secondary_id>U19AT004663</secondary_id>
    <nct_id>NCT01670292</nct_id>
  </id_info>
  <brief_title>Patient Response to Spinal Manipulation</brief_title>
  <acronym>PRiSM</acronym>
  <official_title>Patient Response to Spinal Manipulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Palmer College of Chiropractic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Iowa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Complementary and Integrative Health (NCCIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Palmer College of Chiropractic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a biomechanical study which is Project 1 in the Developmental Center for Clinical and&#xD;
      Translational Research in Chiropractic (DCRC I) (NIH/NCCAM grant 1 U19 AT004663-01; principal&#xD;
      investigator Christine Goertz, DC, PhD). This study is designed to monitor both physiological&#xD;
      and patient self-report outcome variables. In addition, as there is little quantitative&#xD;
      information on Spinal Manipulation Technique procedures reported in clinical trials, the&#xD;
      study is designed to collect preliminary kinetic measures of the spinal manipulation&#xD;
      technique delivery (i.e. force-time profiles).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants with narrowly defined chronic low back pain will be included in this study. Each&#xD;
      participant will be treated 12 times over the course of 6 weeks. The following data will be&#xD;
      collected: participant characteristics that may predict outcome or be modifiers of force used&#xD;
      by provider (gender, age, height, weight, and Body Mass Index); spinal segment load during&#xD;
      the pre-load and thrusting phases (force and moment in the pre-load phase, peak load, and&#xD;
      loading rate); physiological measures (posterior-anterior global stiffness and&#xD;
      flexion-relaxation); patient-centered outcomes of back pain and function; and adverse events.&#xD;
&#xD;
      Study participants (n= 80) will be recruited from the Quad Cities metro area. A team of&#xD;
      experienced chiropractic clinicians working at the Palmer Center for Chiropractic Research&#xD;
      will treat study participants. Each of the study participants will receive 2 High Velocity&#xD;
      Low Amplitude Spinal Manipulation treatment visits per week over a 6 week period. The&#xD;
      physiological assessments will be performed immediately before and after Spinal Manipulation&#xD;
      delivery during treatment visits 1, 5 &amp; 12 (6 sets of assessments in total). During these&#xD;
      same treatment visits, we will also capture the kinetic measures during Spinal Manipulation&#xD;
      delivery for spinal segment load analysis. Participant patient-centered outcomes will be&#xD;
      measured at baseline 1, and treatment visits 6 and 13. For simplicity, data collection time&#xD;
      points will be named as baseline, after 2 weeks, and after 6 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Patient-Centered Outcome Measurement Mean Change After 6 Weeks (VAS, RMDQ)</measure>
    <time_frame>Baseline to 6 weeks</time_frame>
    <description>VAS - Visual Analog Scale - Scale: 0-100 mm (anchors: 0 mm = No Pain, 100 mm = Worst Imaginable Pain). VAS Interpretation: A higher score indicates greater pain intensity. In this study, improvement of 30% from the baseline value was considered clinically significant.&#xD;
RMDQ - Roland Morris disability questionnaire - Scale: 0 (no disability) to 24 (maximum disability). RMDQ Interpretation: Greater levels of disability are reflected by higher scores. In this study, improvement of 30% from the baseline value was considered clinically significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lumbar-spine Stiffness (LSS)</measure>
    <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
    <description>LSS* contains 5 variables: global stiffness (GS, unit: Newton/mm) at L3 from 1) hand palpation 2) a hand-held device &amp; 3) an automated indenter device; global stiffness variation (GSV, unit: Newton/mm) between GS from L1 to L5 from 4) hand palpation &amp; 5) a hand-held device.&#xD;
*LSS Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is high than normal, normal, lower than normal.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lumbar-spine Stiffness (LSS) - Normalized Global Stiffness Variation</measure>
    <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
    <description>LSS contains 2 variables: Palpatory and Handheld device - normalized global stiffness variation (nGSV, unitless).&#xD;
LSS Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, lower than normal.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Flexion-Relaxation Ratio (FRR)</measure>
    <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
    <description>FRR contains 4 variables, which are the average right and left back muscle FRR obtained using 1) maximum EMG during flexion, and 2) maximum EMG during extension to normalize EMG during full flexion; and asymmetry between the right and left back muscle FRRs using 3) maximum EMG during flexion, and 4) maximum EMG during extension to normalize EMG during full flexion&#xD;
FRR Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is high than normal, normal, lower than normal.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Kinetic Measure - Spinal Segment Load (SSL) Force</measure>
    <time_frame>6 weeks</time_frame>
    <description>SSL* contains variables: maximum amplitude (Newton) during preload and peak thrust force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kinetic Measure - Spinal Segment Load (SSL) Moment</measure>
    <time_frame>6 weeks</time_frame>
    <description>SSL* contains variables: maximum amplitude (Newton*Meter for moment) during preload and peak thrust force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kinetic Measure - Spinal Segment Load (SSL) Rate of Loading for Force</measure>
    <time_frame>6 weeks</time_frame>
    <description>SSL* contains variables: rate of loading for force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kinetic Measure - Spinal Segment Load (SSL) Rate of Loading for Moment</measure>
    <time_frame>6 weeks</time_frame>
    <description>SSL* contains variables: rate of loading for moment in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMIS-29 - Patient Reported Outcomes Measurement Information Scale-29: General Health Status Scale</measure>
    <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
    <description>1) The questionnaire contains 7 PROMIS-29 specific items: Anxiety, Depression, Fatigue, Pain Interference, Physical Function, Sleep Disturbance, and Satisfaction with Participation in Social Role (anchors: 1= 'Not at all', 5= 'Very much', higher score is worse).&#xD;
Each PROMIS-29 specific item is reported in raw score (4-20) and scored in T-score (T), which rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10 for a population.&#xD;
On the T-score metric &amp; interpretation:&#xD;
A score of 40 is one SD lower than the mean of the reference population.&#xD;
A score of 60 is one SD higher than the mean of the reference population.&#xD;
For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). Thus a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMIS-29 - Patient Reported Outcomes Measurement Information Scale-29: Global Item, Pain NRS</measure>
    <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
    <description>1) The PROMIS questionnaire contains 1 PROMIS global item: Pain NRS, Scale: 0-10 (anchors: 0 = No Pain, 10 = Worst Imaginable Pain, higher score is worse). The PROMIS global item is not scored but reported in raw score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bothersomeness</measure>
    <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
    <description>Question asked of participants: &quot;During the past week, how bothersome have each of the following symptoms been?&quot; The bothersomeness questionnaire contains two items: a) low back pain &amp; b) leg pain (sciatica).&#xD;
Scale: 0-10 (anchors: 0 = Not at all bothersome, 10 = Extremely bothersome)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Low Back Pain</condition>
  <arm_group>
    <arm_group_label>Experimental: HVLA-SM</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Experimental High Velocity Low Amplitude Spinal Manipulation</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>HVLA-SM</intervention_name>
    <description>High Velocity Low Amplitude Spinal Manipulation</description>
    <arm_group_label>Experimental: HVLA-SM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  NRS score, AVERAGE within the past 24 hours&#xD;
&#xD;
          -  Must be ≥4 at the phone screen or baseline 1 visit&#xD;
&#xD;
          -  Must be ≥2 at phone screen, baseline 1 and baseline 2 visits&#xD;
&#xD;
          -  Roland Morris Disability ≥6&#xD;
&#xD;
          -  Age 21-65&#xD;
&#xD;
          -  Signed informed consent document&#xD;
&#xD;
          -  Chronic (12+ weeks) low back pain&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Compliance concerns&#xD;
&#xD;
          -  No manipulable lesion in L1-L5 or SI joints&#xD;
&#xD;
          -  The absence of typical palpatory characteristics as well as the absence of a global&#xD;
             assessment that would indicate that spinal manipulation is likely to generate a&#xD;
             positive therapeutic effect, even without the presence of standard palpatory findings&#xD;
&#xD;
          -  Ongoing treatment for low back pain by outside provider&#xD;
&#xD;
          -  Comorbid conditions&#xD;
&#xD;
          -  Serious concomitant illness&#xD;
&#xD;
          -  Inflammatory or destructive spinal tissue change&#xD;
&#xD;
          -  Ankylosing Spondylytis&#xD;
&#xD;
          -  Fibromyalgia&#xD;
&#xD;
          -  Rheumatoid Arthritis&#xD;
&#xD;
          -  Confirmed or suspected disc herniation with neurological signs&#xD;
&#xD;
          -  Neuromuscular disease (e.g. Parkinson's, Muscular Dystrophy, Cerebral Palsy, or&#xD;
             Myasthenia gravis&#xD;
&#xD;
          -  Spinal surgery &lt;6 months&#xD;
&#xD;
          -  Suspicion of drug or alcohol dependence or abuse&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  Lower extremity peripheral arterial disease&#xD;
&#xD;
          -  Undetermined, infections or visceral source of low back pain&#xD;
&#xD;
          -  Other comorbid conditions prohibiting treatment and/or testing&#xD;
&#xD;
          -  Safety concerns&#xD;
&#xD;
          -  Bleeding disorders&#xD;
&#xD;
          -  Contraindications to High Velocity Low Amplitude Spinal Manipulation&#xD;
&#xD;
          -  Inability to tolerate or obtain positon for flexion-relaxation test without condition&#xD;
             aggravation&#xD;
&#xD;
          -  Inability to tolerate or perform/receive any study procedure without condition&#xD;
             aggravation&#xD;
&#xD;
          -  Quebec Task Force (QTF) criterion 4-11:&#xD;
&#xD;
          -  QTF 4: Pain + radiation to upper/lower limb with neurologic signs&#xD;
&#xD;
          -  QTF 5: Presumptive compression of a spinal nerve root on a simple roentgenogram&#xD;
&#xD;
          -  QTF 6: Compression of a spinal nerve root confirmed by specific imaging techniques&#xD;
&#xD;
          -  QTF 7: Spinal Stenosis&#xD;
&#xD;
          -  QTF 8: Postsurgical status, 1-6 months after intervention&#xD;
&#xD;
          -  QTF 9: Postsurgical status, &gt;6 months after intervention&#xD;
&#xD;
          -  QTF 10: Chronic pain syndrome&#xD;
&#xD;
          -  QTF 11: Other diagnoses&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Pacemaker or defibrillator&#xD;
&#xD;
          -  Inability to read or verbally comprehend English&#xD;
&#xD;
          -  Joint replacement&#xD;
&#xD;
          -  Use of spinal manipulation within past 4 weeks&#xD;
&#xD;
          -  Sensitivity to adhesive&#xD;
&#xD;
          -  Diagnostic procedures other than x-ray/UA necessary&#xD;
&#xD;
          -  BDI-II ≥29&#xD;
&#xD;
          -  Retention of legal advice and open or pending case related to low back pain&#xD;
&#xD;
          -  BMI ≥40&#xD;
&#xD;
          -  Unwilling to have low back and wrist shaved&#xD;
&#xD;
          -  Moving from Quad Cities area within next 8 weeks&#xD;
&#xD;
          -  Unwilling to postpone treatments for low back pain from another provider&#xD;
&#xD;
          -  Seeking or receiving compensation for any disability&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ting Xia, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Palmer College of Chiropractic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Palmer College of Chiropractic</name>
      <address>
        <city>Davenport</city>
        <state>Iowa</state>
        <zip>52803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139615/</url>
    <description>Study protocol for patient response to spinal manipulation - a prospective observational clinical trial on physiological and patient-centered outcomes in patients with chronic low back pain</description>
  </link>
  <link>
    <url>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593036/</url>
    <description>What is the pain source? A case report of a patient with low back pain and bilateral hip osteonecrosis.</description>
  </link>
  <reference>
    <citation>Xia T, Wilder DG, Gudavalli MR, DeVocht JW, Vining RD, Pohlman KA, Kawchuk GN, Long CR, Goertz CM. Study protocol for patient response to spinal manipulation - a prospective observational clinical trial on physiological and patient-centered outcomes in patients with chronic low back pain. BMC Complement Altern Med. 2014 Aug 8;14:292. doi: 10.1186/1472-6882-14-292.</citation>
    <PMID>25106673</PMID>
  </reference>
  <reference>
    <citation>Minkalis AL, Vining RD. What is the pain source? A case report of a patient with low back pain and bilateral hip osteonecrosis. J Can Chiropr Assoc. 2015 Sep;59(3):300-10.</citation>
    <PMID>26500365</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>August 2, 2012</study_first_submitted>
  <study_first_submitted_qc>August 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2012</study_first_posted>
  <results_first_submitted>April 17, 2017</results_first_submitted>
  <results_first_submitted_qc>October 25, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 5, 2017</results_first_posted>
  <last_update_submitted>October 25, 2017</last_update_submitted>
  <last_update_submitted_qc>October 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Low Back Pain</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>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Once the resulting manuscripts have been published, data sets will be provided for public access. Potential investigators can contact one of the Co-PIs to present their hypothesis, study design, instruments and/or data on which to focus, and resources required. Depending upon the needs and desires of the requesting party, the data that are shared may include analytic tables or de-identified or limited data sets that are transmitted to the requesting parties for additional analyses.</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Experimental: HVLA-SM</title>
          <description>Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation&#xD;
Participants receive treatments of HVLA-SM to the lumbar spine in the side-lying position. Treatment frequency is twice per week for 6 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="82"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="68"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Experimental: HVLA-SM</title>
          <description>Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="82"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44.9" spread="10.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Patient-Centered Outcome Measures</title>
          <description>VAS - Visual Analog Scale: The VAS is a single-item, unidimensional measure for pain. Score interpretations for the VAS include the following cut points: no pain (0 to 4 mm), mild pain (5 to 44 mm), moderate pain (45 to 74 mm), and severe pain (75 to 100 mm).&#xD;
RMDQ - Roland Morris disability questionnaire: The RMDQ consists of 24 questions related to disability, with each question worth one point. Scores can range from 0 (no disability) to 24 (severe disability).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>VAS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.1" spread="18.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RMDQ</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.5" spread="4.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Patient-Centered Outcome Measurement Mean Change After 6 Weeks (VAS, RMDQ)</title>
        <description>VAS - Visual Analog Scale - Scale: 0-100 mm (anchors: 0 mm = No Pain, 100 mm = Worst Imaginable Pain). VAS Interpretation: A higher score indicates greater pain intensity. In this study, improvement of 30% from the baseline value was considered clinically significant.&#xD;
RMDQ - Roland Morris disability questionnaire - Scale: 0 (no disability) to 24 (maximum disability). RMDQ Interpretation: Greater levels of disability are reflected by higher scores. In this study, improvement of 30% from the baseline value was considered clinically significant.</description>
        <time_frame>Baseline to 6 weeks</time_frame>
        <population>82 and 68 participants completed at baseline and after 6 weeks, respectively. Data from all participants (n=82) were used in statistical analysis. The reported data represents the mean change from baseline to week 6.</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental: HVLA-SM</title>
            <description>Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation</description>
          </group>
        </group_list>
        <measure>
          <title>Patient-Centered Outcome Measurement Mean Change After 6 Weeks (VAS, RMDQ)</title>
          <description>VAS - Visual Analog Scale - Scale: 0-100 mm (anchors: 0 mm = No Pain, 100 mm = Worst Imaginable Pain). VAS Interpretation: A higher score indicates greater pain intensity. In this study, improvement of 30% from the baseline value was considered clinically significant.&#xD;
RMDQ - Roland Morris disability questionnaire - Scale: 0 (no disability) to 24 (maximum disability). RMDQ Interpretation: Greater levels of disability are reflected by higher scores. In this study, improvement of 30% from the baseline value was considered clinically significant.</description>
          <population>82 and 68 participants completed at baseline and after 6 weeks, respectively. Data from all participants (n=82) were used in statistical analysis. The reported data represents the mean change from baseline to week 6.</population>
          <units>units on a scale (see description above)</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="82"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mean Reduction in VAS score (mm)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.1" lower_limit="14.1" upper_limit="26.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean Reduction in RMDQ score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" lower_limit="3.7" upper_limit="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Lumbar-spine Stiffness (LSS)</title>
        <description>LSS* contains 5 variables: global stiffness (GS, unit: Newton/mm) at L3 from 1) hand palpation 2) a hand-held device &amp; 3) an automated indenter device; global stiffness variation (GSV, unit: Newton/mm) between GS from L1 to L5 from 4) hand palpation &amp; 5) a hand-held device.&#xD;
*LSS Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is high than normal, normal, lower than normal.</description>
        <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
        <population>82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively. The number of observations at each of the 3 time points for individual measures is equal to or lower than these numbers due to missing data.</population>
        <group_list>
          <group group_id="O1">
            <title>HVLA-SM at Baseline</title>
            <description>Results at Baseline&#xD;
Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation</description>
          </group>
          <group group_id="O2">
            <title>HVLA-SM After 2 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after two weeks.</description>
          </group>
          <group group_id="O3">
            <title>HVLA-SM After 6 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Lumbar-spine Stiffness (LSS)</title>
          <description>LSS* contains 5 variables: global stiffness (GS, unit: Newton/mm) at L3 from 1) hand palpation 2) a hand-held device &amp; 3) an automated indenter device; global stiffness variation (GSV, unit: Newton/mm) between GS from L1 to L5 from 4) hand palpation &amp; 5) a hand-held device.&#xD;
*LSS Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is high than normal, normal, lower than normal.</description>
          <population>82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively. The number of observations at each of the 3 time points for individual measures is equal to or lower than these numbers due to missing data.</population>
          <units>N/mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="82"/>
                <count group_id="O2" value="71"/>
                <count group_id="O3" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>LSS - Palpatory - GS (N/mm) at L3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="1.8"/>
                    <measurement group_id="O2" value="4.3" spread="1.8"/>
                    <measurement group_id="O3" value="4.2" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LSS - Hand-held - GS (N/mm) at L3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" spread="2.1"/>
                    <measurement group_id="O2" value="7.5" spread="1.8"/>
                    <measurement group_id="O3" value="7.6" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LSS - Automated - GS (N/mm) at Ant</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" spread="1.5"/>
                    <measurement group_id="O2" value="5.3" spread="1.4"/>
                    <measurement group_id="O3" value="5.3" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LSS - Palpatory - GSV (N/mm)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="1.5"/>
                    <measurement group_id="O2" value="2.0" spread="1.1"/>
                    <measurement group_id="O3" value="1.9" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LSS - Hand-held - GSV (N/mm)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="1.3"/>
                    <measurement group_id="O2" value="2.1" spread="1.1"/>
                    <measurement group_id="O3" value="2.1" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Lumbar-spine Stiffness (LSS) - Normalized Global Stiffness Variation</title>
        <description>LSS contains 2 variables: Palpatory and Handheld device - normalized global stiffness variation (nGSV, unitless).&#xD;
LSS Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, lower than normal.</description>
        <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>HVLA-SM at Baseline</title>
            <description>Results at Baseline&#xD;
Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation</description>
          </group>
          <group group_id="O2">
            <title>HVLA-SM After 2 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after two weeks.</description>
          </group>
          <group group_id="O3">
            <title>HVLA-SM After 6 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Lumbar-spine Stiffness (LSS) - Normalized Global Stiffness Variation</title>
          <description>LSS contains 2 variables: Palpatory and Handheld device - normalized global stiffness variation (nGSV, unitless).&#xD;
LSS Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, lower than normal.</description>
          <units>unitless</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="82"/>
                <count group_id="O2" value="71"/>
                <count group_id="O3" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>LSS - Palpatory - nGSV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="0.2"/>
                    <measurement group_id="O2" value="0.5" spread="0.2"/>
                    <measurement group_id="O3" value="0.5" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LSS - Hand-held - nGSV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="0.1"/>
                    <measurement group_id="O2" value="0.3" spread="0.1"/>
                    <measurement group_id="O3" value="0.3" spread="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Flexion-Relaxation Ratio (FRR)</title>
        <description>FRR contains 4 variables, which are the average right and left back muscle FRR obtained using 1) maximum EMG during flexion, and 2) maximum EMG during extension to normalize EMG during full flexion; and asymmetry between the right and left back muscle FRRs using 3) maximum EMG during flexion, and 4) maximum EMG during extension to normalize EMG during full flexion&#xD;
FRR Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is high than normal, normal, lower than normal.</description>
        <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>HVLA-SM at Baseline</title>
            <description>Results at Baseline&#xD;
Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation</description>
          </group>
          <group group_id="O2">
            <title>HVLA-SM After 2 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after two weeks.</description>
          </group>
          <group group_id="O3">
            <title>HVLA-SM After 6 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Flexion-Relaxation Ratio (FRR)</title>
          <description>FRR contains 4 variables, which are the average right and left back muscle FRR obtained using 1) maximum EMG during flexion, and 2) maximum EMG during extension to normalize EMG during full flexion; and asymmetry between the right and left back muscle FRRs using 3) maximum EMG during flexion, and 4) maximum EMG during extension to normalize EMG during full flexion&#xD;
FRR Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is high than normal, normal, lower than normal.</description>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="82"/>
                <count group_id="O2" value="71"/>
                <count group_id="O3" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Flexion FRR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="3.7"/>
                    <measurement group_id="O2" value="5.8" spread="5.4"/>
                    <measurement group_id="O3" value="5.5" spread="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Extension FRR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.2" spread="9.5"/>
                    <measurement group_id="O2" value="10.4" spread="11.6"/>
                    <measurement group_id="O3" value="9.4" spread="10.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asymmetry in flexion FRR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="0.5"/>
                    <measurement group_id="O2" value="1.4" spread="0.5"/>
                    <measurement group_id="O3" value="1.4" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asymmetry in extension FRR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="0.7"/>
                    <measurement group_id="O2" value="1.4" spread="0.4"/>
                    <measurement group_id="O3" value="1.4" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kinetic Measure - Spinal Segment Load (SSL) Force</title>
        <description>SSL* contains variables: maximum amplitude (Newton) during preload and peak thrust force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
        <time_frame>6 weeks</time_frame>
        <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively, and a total of 593 SM was delivered during visits 1, 5, and 12. The number of observations for individual measures is lower than the total number of analyzable SM (n=575) due to missing data in corresponding components.</population>
        <group_list>
          <group group_id="O1">
            <title>Anterior-Posterior (X)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the X direction.</description>
          </group>
          <group group_id="O2">
            <title>Side-to-Side (Y)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the Y direction.</description>
          </group>
          <group group_id="O3">
            <title>Head-to-Toe (Z)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the Z direction.</description>
          </group>
          <group group_id="O4">
            <title>Combined</title>
            <description>All participants are in this group, this simply defines the mean Combined force/moment (C).</description>
          </group>
        </group_list>
        <measure>
          <title>Kinetic Measure - Spinal Segment Load (SSL) Force</title>
          <description>SSL* contains variables: maximum amplitude (Newton) during preload and peak thrust force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
          <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively, and a total of 593 SM was delivered during visits 1, 5, and 12. The number of observations for individual measures is lower than the total number of analyzable SM (n=575) due to missing data in corresponding components.</population>
          <units>Newton (N)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Spinal Manipulations</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Spinal Manipulations</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="575"/>
                <count group_id="O2" value="575"/>
                <count group_id="O3" value="575"/>
                <count group_id="O4" value="575"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Preload force (N)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-56.5" spread="87.2"/>
                    <measurement group_id="O2" value="-67.0" spread="55.0"/>
                    <measurement group_id="O3" value="-117.2" spread="59.4"/>
                    <measurement group_id="O4" value="170.3" spread="64.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Peak thrust force (N)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-128.3" spread="163.4"/>
                    <measurement group_id="O2" value="-172.3" spread="141.9"/>
                    <measurement group_id="O3" value="-276.4" spread="137.1"/>
                    <measurement group_id="O4" value="385.1" spread="169.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kinetic Measure - Spinal Segment Load (SSL) Moment</title>
        <description>SSL* contains variables: maximum amplitude (Newton*Meter for moment) during preload and peak thrust force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
        <time_frame>6 weeks</time_frame>
        <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively, and a total of 593 SM was delivered during visits 1, 5, and 12. The number of observations for individual measures is lower than the total number of analyzable SM (n=575) due to missing data in corresponding components.</population>
        <group_list>
          <group group_id="O1">
            <title>Anterior-Posterior (X)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the X direction.</description>
          </group>
          <group group_id="O2">
            <title>Side-to-Side (Y)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the Y direction.</description>
          </group>
          <group group_id="O3">
            <title>Head-to-Toe (Z)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the Z direction.</description>
          </group>
          <group group_id="O4">
            <title>Combined</title>
            <description>All participants are in this group, this simply defines the mean Combined force/moment (C).</description>
          </group>
        </group_list>
        <measure>
          <title>Kinetic Measure - Spinal Segment Load (SSL) Moment</title>
          <description>SSL* contains variables: maximum amplitude (Newton*Meter for moment) during preload and peak thrust force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
          <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively, and a total of 593 SM was delivered during visits 1, 5, and 12. The number of observations for individual measures is lower than the total number of analyzable SM (n=575) due to missing data in corresponding components.</population>
          <units>Newton*Meter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Spinal Manipulations</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Spinal Manipulations</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="575"/>
                <count group_id="O2" value="575"/>
                <count group_id="O3" value="575"/>
                <count group_id="O4" value="575"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Preload moment (N*M)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.8" spread="23.4"/>
                    <measurement group_id="O2" value="-1.0" spread="19.4"/>
                    <measurement group_id="O3" value="-45.4" spread="29.4"/>
                    <measurement group_id="O4" value="58.5" spread="27.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Peak thrust moment (N*M)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.0" spread="46.0"/>
                    <measurement group_id="O2" value="-3.4" spread="39.9"/>
                    <measurement group_id="O3" value="-76.0" spread="42.2"/>
                    <measurement group_id="O4" value="99.5" spread="41.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kinetic Measure - Spinal Segment Load (SSL) Rate of Loading for Force</title>
        <description>SSL* contains variables: rate of loading for force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
        <time_frame>6 weeks</time_frame>
        <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively, and a total of 593 SM was delivered during visits 1, 5, and 12. The number of observations for individual measures is lower than the total number of analyzable SM (n=575) due to missing data in corresponding components.</population>
        <group_list>
          <group group_id="O1">
            <title>Anterior-Posterior (X)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the X direction.</description>
          </group>
          <group group_id="O2">
            <title>Side-to-Side (Y)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the Y direction.</description>
          </group>
          <group group_id="O3">
            <title>Head-to-Toe (Z)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the Z direction.</description>
          </group>
          <group group_id="O4">
            <title>Combined</title>
            <description>All participants are in this group, this simply defines the mean Combined force/moment (C).</description>
          </group>
        </group_list>
        <measure>
          <title>Kinetic Measure - Spinal Segment Load (SSL) Rate of Loading for Force</title>
          <description>SSL* contains variables: rate of loading for force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
          <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively, and a total of 593 SM was delivered during visits 1, 5, and 12. The number of observations for individual measures is lower than the total number of analyzable SM (n=575) due to missing data in corresponding components.</population>
          <units>Newton/second</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Spinal Manipulations</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Spinal Manipulations</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="575"/>
                <count group_id="O2" value="575"/>
                <count group_id="O3" value="575"/>
                <count group_id="O4" value="575"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-599.2" spread="897.1"/>
                    <measurement group_id="O2" value="-598.1" spread="668.8"/>
                    <measurement group_id="O3" value="-1145.2" spread="713.6"/>
                    <measurement group_id="O4" value="1537.5" spread="955.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kinetic Measure - Spinal Segment Load (SSL) Rate of Loading for Moment</title>
        <description>SSL* contains variables: rate of loading for moment in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
        <time_frame>6 weeks</time_frame>
        <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively, and a total of 593 SM was delivered during visits 1, 5, and 12. The number of observations for individual measures is lower than the total number of analyzable SM (n=575) due to missing data in corresponding components.</population>
        <group_list>
          <group group_id="O1">
            <title>Anterior-Posterior (X)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the X direction.</description>
          </group>
          <group group_id="O2">
            <title>Side-to-Side (Y)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the Y direction.</description>
          </group>
          <group group_id="O3">
            <title>Head-to-Toe (Z)</title>
            <description>All participants are in this group, this simply defines the mean force/moment in the Z direction.</description>
          </group>
          <group group_id="O4">
            <title>Combined</title>
            <description>All participants are in this group, this simply defines the mean Combined force/moment (C).</description>
          </group>
        </group_list>
        <measure>
          <title>Kinetic Measure - Spinal Segment Load (SSL) Rate of Loading for Moment</title>
          <description>SSL* contains variables: rate of loading for moment in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).&#xD;
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.&#xD;
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.</description>
          <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively, and a total of 593 SM was delivered during visits 1, 5, and 12. The number of observations for individual measures is lower than the total number of analyzable SM (n=575) due to missing data in corresponding components.</population>
          <units>Newton*Meters/second</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Spinal Manipulations</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Spinal Manipulations</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="575"/>
                <count group_id="O2" value="575"/>
                <count group_id="O3" value="575"/>
                <count group_id="O4" value="575"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.3" spread="201.8"/>
                    <measurement group_id="O2" value="-40.4" spread="183.7"/>
                    <measurement group_id="O3" value="-210.2" spread="159.0"/>
                    <measurement group_id="O4" value="275.2" spread="194.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PROMIS-29 - Patient Reported Outcomes Measurement Information Scale-29: General Health Status Scale</title>
        <description>1) The questionnaire contains 7 PROMIS-29 specific items: Anxiety, Depression, Fatigue, Pain Interference, Physical Function, Sleep Disturbance, and Satisfaction with Participation in Social Role (anchors: 1= 'Not at all', 5= 'Very much', higher score is worse).&#xD;
Each PROMIS-29 specific item is reported in raw score (4-20) and scored in T-score (T), which rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10 for a population.&#xD;
On the T-score metric &amp; interpretation:&#xD;
A score of 40 is one SD lower than the mean of the reference population.&#xD;
A score of 60 is one SD higher than the mean of the reference population.&#xD;
For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). Thus a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.</description>
        <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
        <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively. Number of observations made at the three time points were 82, 70, and 68, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>HVLA-SM at Baseline</title>
            <description>Result at baseline. Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation</description>
          </group>
          <group group_id="O2">
            <title>HVLA-SM After 2 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after two weeks.</description>
          </group>
          <group group_id="O3">
            <title>HVLA-SM After 6 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>PROMIS-29 - Patient Reported Outcomes Measurement Information Scale-29: General Health Status Scale</title>
          <description>1) The questionnaire contains 7 PROMIS-29 specific items: Anxiety, Depression, Fatigue, Pain Interference, Physical Function, Sleep Disturbance, and Satisfaction with Participation in Social Role (anchors: 1= 'Not at all', 5= 'Very much', higher score is worse).&#xD;
Each PROMIS-29 specific item is reported in raw score (4-20) and scored in T-score (T), which rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10 for a population.&#xD;
On the T-score metric &amp; interpretation:&#xD;
A score of 40 is one SD lower than the mean of the reference population.&#xD;
A score of 60 is one SD higher than the mean of the reference population.&#xD;
For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). Thus a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.</description>
          <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively. Number of observations made at the three time points were 82, 70, and 68, respectively.</population>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="82"/>
                <count group_id="O2" value="70"/>
                <count group_id="O3" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>P29 - Anxiety</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.18" spread="8.87"/>
                    <measurement group_id="O2" value="47.93" spread="7.87"/>
                    <measurement group_id="O3" value="46.58" spread="7.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P29 - Depression</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.02" spread="7.78"/>
                    <measurement group_id="O2" value="45.97" spread="7.07"/>
                    <measurement group_id="O3" value="44.38" spread="6.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P29 - Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.72" spread="8.19"/>
                    <measurement group_id="O2" value="51.93" spread="7.84"/>
                    <measurement group_id="O3" value="50.09" spread="7.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P-29 - Pain Interference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.26" spread="5.70"/>
                    <measurement group_id="O2" value="57.78" spread="6.37"/>
                    <measurement group_id="O3" value="55.12" spread="7.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P29 - Physical Function</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.31" spread="3.93"/>
                    <measurement group_id="O2" value="32.29" spread="3.84"/>
                    <measurement group_id="O3" value="30.07" spread="3.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P29- Sleep Disturbance</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.23" spread="3.13"/>
                    <measurement group_id="O2" value="51.11" spread="3.23"/>
                    <measurement group_id="O3" value="51.79" spread="3.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P29 - Satisfaction w/ Participation in Social Role</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.45" spread="6.84"/>
                    <measurement group_id="O2" value="46.51" spread="6.75"/>
                    <measurement group_id="O3" value="49.75" spread="7.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PROMIS-29 - Patient Reported Outcomes Measurement Information Scale-29: Global Item, Pain NRS</title>
        <description>1) The PROMIS questionnaire contains 1 PROMIS global item: Pain NRS, Scale: 0-10 (anchors: 0 = No Pain, 10 = Worst Imaginable Pain, higher score is worse). The PROMIS global item is not scored but reported in raw score.</description>
        <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
        <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively. Number of observations made at the three time points were 82, 70, and 68, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>HVLA-SM at Baseline</title>
            <description>Result at baseline. Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation</description>
          </group>
          <group group_id="O2">
            <title>HVLA-SM After 2 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after two weeks.</description>
          </group>
          <group group_id="O3">
            <title>HVLA-SM After 6 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>PROMIS-29 - Patient Reported Outcomes Measurement Information Scale-29: Global Item, Pain NRS</title>
          <description>1) The PROMIS questionnaire contains 1 PROMIS global item: Pain NRS, Scale: 0-10 (anchors: 0 = No Pain, 10 = Worst Imaginable Pain, higher score is worse). The PROMIS global item is not scored but reported in raw score.</description>
          <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively. Number of observations made at the three time points were 82, 70, and 68, respectively.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="82"/>
                <count group_id="O2" value="70"/>
                <count group_id="O3" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.57" spread="1.63"/>
                    <measurement group_id="O2" value="4.46" spread="1.95"/>
                    <measurement group_id="O3" value="3.59" spread="2.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bothersomeness</title>
        <description>Question asked of participants: &quot;During the past week, how bothersome have each of the following symptoms been?&quot; The bothersomeness questionnaire contains two items: a) low back pain &amp; b) leg pain (sciatica).&#xD;
Scale: 0-10 (anchors: 0 = Not at all bothersome, 10 = Extremely bothersome)</description>
        <time_frame>Baseline, 2 weeks, 6 weeks</time_frame>
        <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively. Number of observations made at the three time points were 82, 70, and 68, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>HVLA-SM at Baseline</title>
            <description>Results at Baseline&#xD;
Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation</description>
          </group>
          <group group_id="O2">
            <title>HVLA-SM After 2 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after two weeks.</description>
          </group>
          <group group_id="O3">
            <title>HVLA-SM After 6 Weeks</title>
            <description>There is only one group/arm, this is the data for the same group of participants after six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Bothersomeness</title>
          <description>Question asked of participants: &quot;During the past week, how bothersome have each of the following symptoms been?&quot; The bothersomeness questionnaire contains two items: a) low back pain &amp; b) leg pain (sciatica).&#xD;
Scale: 0-10 (anchors: 0 = Not at all bothersome, 10 = Extremely bothersome)</description>
          <population>Note: 82, 71 and 68 participants completed at baseline, after 2 weeks and after 6 weeks, respectively. Number of observations made at the three time points were 82, 70, and 68, respectively.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="82"/>
                <count group_id="O2" value="70"/>
                <count group_id="O3" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Low Back Pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.18" spread="1.93"/>
                    <measurement group_id="O2" value="4.80" spread="2.14"/>
                    <measurement group_id="O3" value="3.63" spread="2.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leg Pain (Sciatica)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.29" spread="3.18"/>
                    <measurement group_id="O2" value="2.61" spread="2.91"/>
                    <measurement group_id="O3" value="1.94" spread="2.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 weeks</time_frame>
      <desc>Any untoward medical occurrence that may present itself during the conduct of the study which may or may not have a causal relationship with the study procedures.&#xD;
*The total number of AEs may exceed the total # of people affected because some people experienced multiple AEs.</desc>
      <group_list>
        <group group_id="E1">
          <title>Experimental: HVLA-SM*</title>
          <description>Experimental High Velocity Low Amplitude Spinal Manipulation&#xD;
HVLA-SM: High Velocity Low Amplitude Spinal Manipulation</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="74" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sinus congestion/upper respiratory symptoms/allergy</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Insect bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Gastrointestinal symptoms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Nausea and tooth/facial pain and sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Nausea and back pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Asthma and lower respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection and allergy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hemorrhoids and nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Low back pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Neck and back pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Headache and neck/back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Back pain and extremity pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Thoracic and low back pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Neck, back and extremity pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Back and extremity pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Neck and extremity pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pain/stiffness in the extremities</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lower/extremity pain/stiffness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Neck and back pain and extremity pain and headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Back pain/stiffness and numbness/tingling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Back pain and extremity pain and numbness/tingling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Ting Xia</name_or_title>
      <organization>Palmer Center for Chiropractic Research</organization>
      <phone>563-884-5161</phone>
      <email>ting.xia@palmer.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01670292
org study id: PRiSM Study
secondary id: U19AT004663
nct id: NCT01670292
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This is a biomechanical study which is Project 1 in the Developmental Center for Clinical and
      Translational Research in Chiropractic (DCRC I) (NIH/NCCAM grant 1 U19 AT004663-01; principal
      investigator Christine Goertz, DC, PhD). This study is designed to monitor both physiological
      and patient self-report outcome variables. In addition, as there is little quantitative
      information on Spinal Manipulation Technique procedures reported in clinical trials, the
      study is designed to collect preliminary kinetic measures of the spinal manipulation
      technique delivery (i.e. force-time profiles).
Participants with narrowly defined chronic low back pain will be included in this study. Each
      participant will be treated 12 times over the course of 6 weeks. The following data will be
      collected: participant characteristics that may predict outcome or be modifiers of force used
      by provider (gender, age, height, weight, and Body Mass Index); spinal segment load during
      the pre-load and thrusting phases (force and moment in the pre-load phase, peak load, and
      loading rate); physiological measures (posterior-anterior global stiffness and
      flexion-relaxation); patient-centered outcomes of back pain and function; and adverse events.

      Study participants (n= 80) will be recruited from the Quad Cities metro area. A team of
      experienced chiropractic clinicians working at the Palmer Center for Chiropractic Research
      will treat study participants. Each of the study participants will receive 2 High Velocity
      Low Amplitude Spinal Manipulation treatment visits per week over a 6 week period. The
      physiological assessments will be performed immediately before and after Spinal Manipulation
      delivery during treatment visits 1, 5 & 12 (6 sets of assessments in total). During these
      same treatment visits, we will also capture the kinetic measures during Spinal Manipulation
      delivery for spinal segment load analysis. Participant patient-centered outcomes will be
      measured at baseline 1, and treatment visits 6 and 13. For simplicity, data collection time
      points will be named as baseline, after 2 weeks, and after 6 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Patient-Centered Outcome Measurement Mean Change After 6 Weeks (VAS, RMDQ)
time frame: Baseline to 6 weeks
description: VAS - Visual Analog Scale - Scale: 0-100 mm (anchors: 0 mm = No Pain, 100 mm = Worst Imaginable Pain). VAS Interpretation: A higher score indicates greater pain intensity. In this study, improvement of 30% from the baseline value was considered clinically significant.
RMDQ - Roland Morris disability questionnaire - Scale: 0 (no disability) to 24 (maximum disability). RMDQ Interpretation: Greater levels of disability are reflected by higher scores. In this study, improvement of 30% from the baseline value was considered clinically significant.
measure: Lumbar-spine Stiffness (LSS)
time frame: Baseline, 2 weeks, 6 weeks
description: LSS* contains 5 variables: global stiffness (GS, unit: Newton/mm) at L3 from 1) hand palpation 2) a hand-held device & 3) an automated indenter device; global stiffness variation (GSV, unit: Newton/mm) between GS from L1 to L5 from 4) hand palpation & 5) a hand-held device.
*LSS Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is high than normal, normal, lower than normal.
measure: Lumbar-spine Stiffness (LSS) - Normalized Global Stiffness Variation
time frame: Baseline, 2 weeks, 6 weeks
description: LSS contains 2 variables: Palpatory and Handheld device - normalized global stiffness variation (nGSV, unitless).
LSS Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, lower than normal.
measure: Flexion-Relaxation Ratio (FRR)
time frame: Baseline, 2 weeks, 6 weeks
description: FRR contains 4 variables, which are the average right and left back muscle FRR obtained using 1) maximum EMG during flexion, and 2) maximum EMG during extension to normalize EMG during full flexion; and asymmetry between the right and left back muscle FRRs using 3) maximum EMG during flexion, and 4) maximum EMG during extension to normalize EMG during full flexion
FRR Interpretation: The values of the outcome depend on testing procedure, instruction to participants, and equipment. Currently there is no consensus regarding what value is high than normal, normal, lower than normal.
measure: Kinetic Measure - Spinal Segment Load (SSL) Force
time frame: 6 weeks
description: SSL* contains variables: maximum amplitude (Newton) during preload and peak thrust force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.
measure: Kinetic Measure - Spinal Segment Load (SSL) Moment
time frame: 6 weeks
description: SSL* contains variables: maximum amplitude (Newton*Meter for moment) during preload and peak thrust force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.
measure: Kinetic Measure - Spinal Segment Load (SSL) Rate of Loading for Force
time frame: 6 weeks
description: SSL* contains variables: rate of loading for force in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.
measure: Kinetic Measure - Spinal Segment Load (SSL) Rate of Loading for Moment
time frame: 6 weeks
description: SSL* contains variables: rate of loading for moment in anterior-posterior (X), side-to-side (Y), head-to-toe direction (Z) and combined force (C).
*Interpretation: the purpose of the outcomes is to quantify force-time profile of SM. The values of the outcome depend on the doctor who delivers SM, location and direction of SM, participant body position, and equipment. Currently there is no consensus regarding what value is higher than normal, normal, or lower than normal.
Sign convention: because patient position would affect the sign of some measurements, the right side up position was used as the reference position (i.e., the affected measurements assessed in the left side up position had their sign inverted) in order to calculate mean and SD. The value reported is the change from baseline to week 6.
measure: PROMIS-29 - Patient Reported Outcomes Measurement Information Scale-29: General Health Status Scale
time frame: Baseline, 2 weeks, 6 weeks
description: 1) The questionnaire contains 7 PROMIS-29 specific items: Anxiety, Depression, Fatigue, Pain Interference, Physical Function, Sleep Disturbance, and Satisfaction with Participation in Social Role (anchors: 1= 'Not at all', 5= 'Very much', higher score is worse).
Each PROMIS-29 specific item is reported in raw score (4-20) and scored in T-score (T), which rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10 for a population.
On the T-score metric & interpretation:
A score of 40 is one SD lower than the mean of the reference population.
A score of 60 is one SD higher than the mean of the reference population.
For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). Thus a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.
measure: PROMIS-29 - Patient Reported Outcomes Measurement Information Scale-29: Global Item, Pain NRS
time frame: Baseline, 2 weeks, 6 weeks
description: 1) The PROMIS questionnaire contains 1 PROMIS global item: Pain NRS, Scale: 0-10 (anchors: 0 = No Pain, 10 = Worst Imaginable Pain, higher score is worse). The PROMIS global item is not scored but reported in raw score.
measure: Bothersomeness
time frame: Baseline, 2 weeks, 6 weeks
description: Question asked of participants: "During the past week, how bothersome have each of the following symptoms been?" The bothersomeness questionnaire contains two items: a) low back pain & b) leg pain (sciatica).
Scale: 0-10 (anchors: 0 = Not at all bothersome, 10 = Extremely bothersome)
arm group label: Experimental: HVLA-SM
arm group type: Other
description: Experimental High Velocity Low Amplitude Spinal Manipulation
intervention type: Other
intervention name: HVLA-SM
description: High Velocity Low Amplitude Spinal Manipulation
arm group label: Experimental: HVLA-SM
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ting Xia, PhD
role: Principal Investigator
affiliation: Palmer College of Chiropractic
facility: 
country: United States
url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139615/
description: Study protocol for patient response to spinal manipulation - a prospective observational clinical trial on physiological and patient-centered outcomes in patients with chronic low back pain
url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593036/
description: What is the pain source? A case report of a patient with low back pain and bilateral hip osteonecrosis.
citation: Xia T, Wilder DG, Gudavalli MR, DeVocht JW, Vining RD, Pohlman KA, Kawchuk GN, Long CR, Goertz CM. Study protocol for patient response to spinal manipulation - a prospective observational clinical trial on physiological and patient-centered outcomes in patients with chronic low back pain. BMC Complement Altern Med. 2014 Aug 8;14:292. doi: 10.1186/1472-6882-14-292.
PMID: 25106673
citation: Minkalis AL, Vining RD. What is the pain source? A case report of a patient with low back pain and bilateral hip osteonecrosis. J Can Chiropr Assoc. 2015 Sep;59(3):300-10.
PMID: 26500365
responsible party type: Sponsor
mesh term: Back Pain
mesh term: Low Back Pain
sharing ipd: Yes
ipd description: Once the resulting manuscripts have been published, data sets will be provided for public access. Potential investigators can contact one of the Co-PIs to present their hypothesis, study design, instruments and/or data on which to focus, and resources required. Depending upon the needs and desires of the requesting party, the data that are shared may include analytic tables or de-identified or limited data sets that are transmitted to the requesting parties for additional analyses.
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 