<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/NCT03282565</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00133860</org_study_id>
    <secondary_id>R21HD092614</secondary_id>
    <nct_id>NCT03282565</nct_id>
  </id_info>
  <brief_title>Functional Resistance Training to Improve Knee Function After ACL Reconstruction</brief_title>
  <official_title>Functional Resistance Training During Gait: A Novel Intervention to Improve Knee Knee Function After ACL Reconstruction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine if thigh muscle weakness and the lack of muscle&#xD;
      activation that accompanies ACL injury and reconstruction can be improved with functional&#xD;
      resistance training.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Profound quadriceps weakness is ubiquitous after anterior cruciate ligament (ACL)&#xD;
      reconstruction, and current rehabilitation approaches are not successful in optimizing&#xD;
      quadriceps strength and knee function even years after the surgery. We hypothesize that&#xD;
      suboptimal strength and functional outcomes after ACL surgery are due to the lack of&#xD;
      task-specific exercise elements during strength training. This application seeks to assess&#xD;
      whether progressive functional resistance training during gait will significantly improve&#xD;
      quadriceps function, neural excitability, and knee mechanics during gait. The proposed&#xD;
      studies will not only lay the foundation for a novel training paradigm, but will also improve&#xD;
      our understanding of the mechanisms mediating neuromuscular and biomechanical changes after&#xD;
      functional resistance training.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 17, 2018</start_date>
  <completion_date type="Actual">December 1, 2020</completion_date>
  <primary_completion_date type="Actual">December 1, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quadriceps Muscle Strength</measure>
    <time_frame>Pre-test measurements were taken at ~9-10 weeks after ACL reconstruction and Post-test measurements were taken at ~18-20 weeks after ACL reconstruction.</time_frame>
    <description>Isometric quadriceps strength was measured with the knee at 60 degrees using an isokinetic dynamometer prior to the intervention and immediately after the intervention. Post-test minus pre-test change scores were calculated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quadriceps Voluntary Activation</measure>
    <time_frame>Immediately after the intervention or approximately 18-20 weeks after ACL reconstruction</time_frame>
    <description>Quadriceps voluntary activation was measured using the burst superimposition technique and calculated using the central activation ratio (CAR). The CAR formula is calculated using the peak torque generated immediately prior to the delivery of the stimulus (or the maximum voluntary isometric contraction, MVIC) being divided by the peak torque generated as a result of the electrical stimulus (MVIC plus superimposed burst) and then multiplied by 100. Equation is: MVIC/(MVIC + superimposed burst) × 100. A CAR of 100 represents complete volitional quadriceps activation.&#xD;
Voluntary activation was quantified immediately after the intervenapproximately 9-10 weeks after the int from baseline to the end of intervention will be assessed and compared between groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Knee Flexion Angle Symmetry</measure>
    <time_frame>Pre-intervention values were recorded at ~9-10 weeks after ACL reconstruction and before the start of the intervention. Post-intervention values were recorded after the 8-week intervention (~18-20 weeks after ACL reconstruction)</time_frame>
    <description>The knee flexion angle (measured in degrees) during the stance phase was gathered for both limbs using three dimension motion capture and recorded while subjects walked overground. A knee flexion angle symmetry score was computed using the following formula: ensemble average of knee flexion angle of ACL limb minus the ensemble average of knee flexion angle of the non-ACL limb. The mean difference between pre-intervention and post-intervention (post minus pre) knee flexion symmetry scores were calculated for each group. Higher values suggest greater increases in knee flexion angle symmetry from pre-intervention to post-intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Knee Moment Symmetry</measure>
    <time_frame>Pre-intervention scores were recorded prior to the start of the intervention and approximately 9-10 weeks after ACL reconstruction. Post-intervention scores were recorded after the 8 week intervention or approximately 18-20 weeks after ACL reconstruction</time_frame>
    <description>The sagittal plane knee moment (units Nm) during the stance phase was gathered for both limbs using three dimensional motion capture and recorded while subjects walk overground. A symmetry score was computed using the following formula: ensemble average of the knee moment of the ACL limb (Nm) - ensemble average of the knee moment of the non-ACL limb (Nm). The mean difference between pre-intervention and post-intervention knee moment symmetry scores (post minus pre) were calculated for each group. Higher values represent the greater increases in knee moment symmetry from pre-intervention to post-intervention.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Anterior Cruciate Ligament Injury</condition>
  <arm_group>
    <arm_group_label>Functional Resistance Training with a Brace</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive functional resistance training via a knee brace while walking on a treadmill 2-3 times a week for about 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Functional Resistance Training with Elastic Band</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive functional resistance training via an elastic band attached at the ankle while walking on a treadmill 2-3 times a week for about 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Participants will while on a treadmill without an applied resistance 2-3 times a week for about 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Functional Resistance Training with Brace</intervention_name>
    <description>A brace will be strapped to the leg and apply resistance across the knee while subjects walk on a treadmill.</description>
    <arm_group_label>Functional Resistance Training with a Brace</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>A brace will be strapped to the leg and will not apply resistance across the knee while subjects walk on a treadmill.</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Functional Resistance Training with Elastic Band</intervention_name>
    <description>An elastic band will be strapped to the leg and apply resistance across the knee while subjects walk on a treadmill.</description>
    <arm_group_label>Functional Resistance Training with Elastic Band</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged 14-40 years&#xD;
&#xD;
          -  suffered an acute, complete ACL rupture&#xD;
&#xD;
          -  willingness to participate in testing and follow-up as outlined in the protocol&#xD;
&#xD;
          -  English-speaking&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  inability to provide written informed consent&#xD;
&#xD;
          -  female subjects who are pregnant or are planning to become pregnant&#xD;
&#xD;
          -  previous ACL injury&#xD;
&#xD;
          -  previous surgery to either knee&#xD;
&#xD;
          -  bony fracture accompanying ACL injury&#xD;
&#xD;
          -  patients who experienced a knee dislocation;&#xD;
&#xD;
          -  patients who are contraindicated for transcranial magnetic stimulation (e.g., metal&#xD;
             implants in head, unexplained recurrent headaches, history of seizures, epileptogenic&#xD;
             drugs, active psychiatric illness, etc.).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Riann Palmieri-Smith, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Chandramouli Krishnan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <results_first_submitted>November 4, 2021</results_first_submitted>
  <results_first_submitted_qc>January 13, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">January 18, 2022</results_first_posted>
  <last_update_submitted>January 13, 2022</last_update_submitted>
  <last_update_submitted_qc>January 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Riann Palmieri-Smith</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>ACL</keyword>
  <keyword>Quadriceps</keyword>
  <keyword>Muscle</keyword>
  <keyword>Resistance Training</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anterior Cruciate Ligament Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 13, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03282565/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 13, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03282565/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Functional Resistance Training With Brace</title>
          <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: A customized knee brace was strapped to the leg and applied resistance during knee flexion and extension while subjects walked on a treadmill.</description>
        </group>
        <group group_id="P2">
          <title>Functional Resistance Training With Elastic Band</title>
          <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: An elastic band strapped to the ankle provided resistance during knee extension while subjects walked on a treadmill.</description>
        </group>
        <group group_id="P3">
          <title>Control</title>
          <description>Participants walked on a treadmill without an applied resistance 2-3 times a week for about 8 weeks.&#xD;
Control: A knee brace was strapped to the leg and did not apply resistance while subjects walked on a treadmill.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>COVID-19 Research Shutdown</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Functional Resistance Training With Brace</title>
          <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: A customized knee brace was strapped to the leg and applied resistance during knee flexion and extension while subjects walked on a treadmill.</description>
        </group>
        <group group_id="B2">
          <title>Functional Resistance Training With Elastic Band</title>
          <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: An elastic band strapped to the ankle provided resistance during knee extension while subjects walked on a treadmill.</description>
        </group>
        <group group_id="B3">
          <title>Control</title>
          <description>Participants walked on a treadmill without an applied resistance 2-3 times a week for about 8 weeks.&#xD;
Control: A knee brace was strapped to the leg and did not apply resistance while subjects walked on a treadmill.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="10"/>
            <count group_id="B4" value="30"/>
          </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="18.8" spread="6.2"/>
                    <measurement group_id="B2" value="22.1" spread="4.5"/>
                    <measurement group_id="B3" value="20.4" spread="5.6"/>
                    <measurement group_id="B4" value="20.4" spread="5.4"/>
                  </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="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="174" spread="11.2"/>
                    <measurement group_id="B2" value="172.3" spread="7.9"/>
                    <measurement group_id="B3" value="169.8" spread="9.0"/>
                    <measurement group_id="B4" value="172.0" spread="9.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mass</title>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.1" spread="10.5"/>
                    <measurement group_id="B2" value="70.3" spread="12.2"/>
                    <measurement group_id="B3" value="70.2" spread="13.3"/>
                    <measurement group_id="B4" value="70.2" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time Since Surgery to Baseline Study Testing</title>
          <units>weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.9" spread="2.6"/>
                    <measurement group_id="B2" value="9.5" spread="2.5"/>
                    <measurement group_id="B3" value="10.3" spread="3.1"/>
                    <measurement group_id="B4" value="9.6" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Quadriceps Muscle Strength</title>
        <description>Isometric quadriceps strength was measured with the knee at 60 degrees using an isokinetic dynamometer prior to the intervention and immediately after the intervention. Post-test minus pre-test change scores were calculated.</description>
        <time_frame>Pre-test measurements were taken at ~9-10 weeks after ACL reconstruction and Post-test measurements were taken at ~18-20 weeks after ACL reconstruction.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Functional Resistance Training With Brace</title>
            <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: A customized knee brace was strapped to the leg and applied resistance during knee flexion and extension while subjects walked on a treadmill.</description>
          </group>
          <group group_id="O2">
            <title>Functional Resistance Training With Elastic Band</title>
            <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: An elastic band strapped to the ankle provided resistance during knee extension while subjects walked on a treadmill.</description>
          </group>
          <group group_id="O3">
            <title>Control</title>
            <description>Participants walked on a treadmill without an applied resistance 2-3 times a week for about 8 weeks.&#xD;
Control: A knee brace was strapped to the leg and did not apply resistance while subjects walked on a treadmill.</description>
          </group>
        </group_list>
        <measure>
          <title>Quadriceps Muscle Strength</title>
          <description>Isometric quadriceps strength was measured with the knee at 60 degrees using an isokinetic dynamometer prior to the intervention and immediately after the intervention. Post-test minus pre-test change scores were calculated.</description>
          <units>Nm/Kg</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".674" spread=".124"/>
                    <measurement group_id="O2" value=".398" spread=".130"/>
                    <measurement group_id="O3" value=".279" spread=".130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Quadriceps Voluntary Activation</title>
        <description>Quadriceps voluntary activation was measured using the burst superimposition technique and calculated using the central activation ratio (CAR). The CAR formula is calculated using the peak torque generated immediately prior to the delivery of the stimulus (or the maximum voluntary isometric contraction, MVIC) being divided by the peak torque generated as a result of the electrical stimulus (MVIC plus superimposed burst) and then multiplied by 100. Equation is: MVIC/(MVIC + superimposed burst) × 100. A CAR of 100 represents complete volitional quadriceps activation.&#xD;
Voluntary activation was quantified immediately after the intervenapproximately 9-10 weeks after the int from baseline to the end of intervention will be assessed and compared between groups.</description>
        <time_frame>Immediately after the intervention or approximately 18-20 weeks after ACL reconstruction</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Functional Resistance Training With Brace</title>
            <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: A customized knee brace was strapped to the leg and applied resistance during knee flexion and extension while subjects walked on a treadmill.</description>
          </group>
          <group group_id="O2">
            <title>Functional Resistance Training With Elastic Band</title>
            <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: An elastic band strapped to the ankle provided resistance during knee extension while subjects walked on a treadmill.</description>
          </group>
          <group group_id="O3">
            <title>Control</title>
            <description>Participants walked on a treadmill without an applied resistance 2-3 times a week for about 8 weeks.&#xD;
Control: A knee brace was strapped to the leg and did not apply resistance while subjects walked on a treadmill.</description>
          </group>
        </group_list>
        <measure>
          <title>Quadriceps Voluntary Activation</title>
          <description>Quadriceps voluntary activation was measured using the burst superimposition technique and calculated using the central activation ratio (CAR). The CAR formula is calculated using the peak torque generated immediately prior to the delivery of the stimulus (or the maximum voluntary isometric contraction, MVIC) being divided by the peak torque generated as a result of the electrical stimulus (MVIC plus superimposed burst) and then multiplied by 100. Equation is: MVIC/(MVIC + superimposed burst) × 100. A CAR of 100 represents complete volitional quadriceps activation.&#xD;
Voluntary activation was quantified immediately after the intervenapproximately 9-10 weeks after the int from baseline to the end of intervention will be assessed and compared between groups.</description>
          <units>percentage of activation</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.19" spread="6.56"/>
                    <measurement group_id="O2" value="69.55" spread="7.72"/>
                    <measurement group_id="O3" value="68.29" spread="7.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Knee Flexion Angle Symmetry</title>
        <description>The knee flexion angle (measured in degrees) during the stance phase was gathered for both limbs using three dimension motion capture and recorded while subjects walked overground. A knee flexion angle symmetry score was computed using the following formula: ensemble average of knee flexion angle of ACL limb minus the ensemble average of knee flexion angle of the non-ACL limb. The mean difference between pre-intervention and post-intervention (post minus pre) knee flexion symmetry scores were calculated for each group. Higher values suggest greater increases in knee flexion angle symmetry from pre-intervention to post-intervention.</description>
        <time_frame>Pre-intervention values were recorded at ~9-10 weeks after ACL reconstruction and before the start of the intervention. Post-intervention values were recorded after the 8-week intervention (~18-20 weeks after ACL reconstruction)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Functional Resistance Training With Brace</title>
            <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: A customized knee brace was strapped to the leg and applied resistance during knee flexion and extension while subjects walked on a treadmill.</description>
          </group>
          <group group_id="O2">
            <title>Functional Resistance Training With Elastic Band</title>
            <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: An elastic band strapped to the ankle provided resistance during knee extension while subjects walked on a treadmill.</description>
          </group>
          <group group_id="O3">
            <title>Control</title>
            <description>Participants walked on a treadmill without an applied resistance 2-3 times a week for about 8 weeks.&#xD;
Control: A knee brace was strapped to the leg and did not apply resistance while subjects walked on a treadmill.</description>
          </group>
        </group_list>
        <measure>
          <title>Knee Flexion Angle Symmetry</title>
          <description>The knee flexion angle (measured in degrees) during the stance phase was gathered for both limbs using three dimension motion capture and recorded while subjects walked overground. A knee flexion angle symmetry score was computed using the following formula: ensemble average of knee flexion angle of ACL limb minus the ensemble average of knee flexion angle of the non-ACL limb. The mean difference between pre-intervention and post-intervention (post minus pre) knee flexion symmetry scores were calculated for each group. Higher values suggest greater increases in knee flexion angle symmetry from pre-intervention to post-intervention.</description>
          <units>Angle Symmetry (degrees)</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="9"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.230" lower_limit="0.658" upper_limit="5.803"/>
                    <measurement group_id="O2" value="0.556" lower_limit="-0.857" upper_limit="1.970"/>
                    <measurement group_id="O3" value="0.846" lower_limit="-0.917" upper_limit="2.608"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Knee Moment Symmetry</title>
        <description>The sagittal plane knee moment (units Nm) during the stance phase was gathered for both limbs using three dimensional motion capture and recorded while subjects walk overground. A symmetry score was computed using the following formula: ensemble average of the knee moment of the ACL limb (Nm) - ensemble average of the knee moment of the non-ACL limb (Nm). The mean difference between pre-intervention and post-intervention knee moment symmetry scores (post minus pre) were calculated for each group. Higher values represent the greater increases in knee moment symmetry from pre-intervention to post-intervention.</description>
        <time_frame>Pre-intervention scores were recorded prior to the start of the intervention and approximately 9-10 weeks after ACL reconstruction. Post-intervention scores were recorded after the 8 week intervention or approximately 18-20 weeks after ACL reconstruction</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Functional Resistance Training With Brace</title>
            <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: A customized knee brace was strapped to the leg and applied resistance during knee flexion and extension while subjects walked on a treadmill.</description>
          </group>
          <group group_id="O2">
            <title>Functional Resistance Training With Elastic Band</title>
            <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: An elastic band strapped to the ankle provided resistance during knee extension while subjects walked on a treadmill.</description>
          </group>
          <group group_id="O3">
            <title>Control</title>
            <description>Participants walked on a treadmill without an applied resistance 2-3 times a week for about 8 weeks.&#xD;
Control: A knee brace was strapped to the leg and did not apply resistance while subjects walked on a treadmill.</description>
          </group>
        </group_list>
        <measure>
          <title>Knee Moment Symmetry</title>
          <description>The sagittal plane knee moment (units Nm) during the stance phase was gathered for both limbs using three dimensional motion capture and recorded while subjects walk overground. A symmetry score was computed using the following formula: ensemble average of the knee moment of the ACL limb (Nm) - ensemble average of the knee moment of the non-ACL limb (Nm). The mean difference between pre-intervention and post-intervention knee moment symmetry scores (post minus pre) were calculated for each group. Higher values represent the greater increases in knee moment symmetry from pre-intervention to post-intervention.</description>
          <units>Moment Symmetry (Nm)</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="9"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".0144" lower_limit="-0.057" upper_limit="0.086"/>
                    <measurement group_id="O2" value="0.132" lower_limit="0.0408" upper_limit="0.224"/>
                    <measurement group_id="O3" value="-0.042" lower_limit="-0.078" upper_limit="-0.0074"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected during the course of the study. The timeframe of the study was approximately 5 months. Adverse events during a period from about 8 weeks after ACL reconstruction to about 28 weeks after reconstruction.</time_frame>
      <desc>Does not differ from clinical trials.gov</desc>
      <group_list>
        <group group_id="E1">
          <title>Functional Resistance Training With Brace</title>
          <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: A customized knee brace was strapped to the leg and applied resistance during knee flexion and extension while subjects walked on a treadmill.</description>
        </group>
        <group group_id="E2">
          <title>Functional Resistance Training With Elastic Band</title>
          <description>Participants received functional resistance training while walking on a treadmill 2-3 times a week for 8 weeks.&#xD;
Functional Resistance Training: An elastic band strapped to the ankle provided resistance during knee extension while subjects walked on a treadmill.</description>
        </group>
        <group group_id="E3">
          <title>Control</title>
          <description>Participants walked on a treadmill without an applied resistance 2-3 times a week for about 8 weeks.&#xD;
Control: A knee brace was strapped to the leg and did not apply resistance while subjects walked on a treadmill.</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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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. Riann Palmieri-Smith</name_or_title>
      <organization>University of Michigan</organization>
      <phone>734-615-3154</phone>
      <email>riannp@umich.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/NCT03282565
org study id: HUM00133860
secondary id: R21HD092614
nct id: NCT03282565
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to examine if thigh muscle weakness and the lack of muscle
      activation that accompanies ACL injury and reconstruction can be improved with functional
      resistance training.
Profound quadriceps weakness is ubiquitous after anterior cruciate ligament (ACL)
      reconstruction, and current rehabilitation approaches are not successful in optimizing
      quadriceps strength and knee function even years after the surgery. We hypothesize that
      suboptimal strength and functional outcomes after ACL surgery are due to the lack of
      task-specific exercise elements during strength training. This application seeks to assess
      whether progressive functional resistance training during gait will significantly improve
      quadriceps function, neural excitability, and knee mechanics during gait. The proposed
      studies will not only lay the foundation for a novel training paradigm, but will also improve
      our understanding of the mechanisms mediating neuromuscular and biomechanical changes after
      functional resistance training.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Quadriceps Muscle Strength
time frame: Pre-test measurements were taken at ~9-10 weeks after ACL reconstruction and Post-test measurements were taken at ~18-20 weeks after ACL reconstruction.
description: Isometric quadriceps strength was measured with the knee at 60 degrees using an isokinetic dynamometer prior to the intervention and immediately after the intervention. Post-test minus pre-test change scores were calculated.
measure: Quadriceps Voluntary Activation
time frame: Immediately after the intervention or approximately 18-20 weeks after ACL reconstruction
description: Quadriceps voluntary activation was measured using the burst superimposition technique and calculated using the central activation ratio (CAR). The CAR formula is calculated using the peak torque generated immediately prior to the delivery of the stimulus (or the maximum voluntary isometric contraction, MVIC) being divided by the peak torque generated as a result of the electrical stimulus (MVIC plus superimposed burst) and then multiplied by 100. Equation is: MVIC/(MVIC + superimposed burst) × 100. A CAR of 100 represents complete volitional quadriceps activation.
Voluntary activation was quantified immediately after the intervenapproximately 9-10 weeks after the int from baseline to the end of intervention will be assessed and compared between groups.
measure: Knee Flexion Angle Symmetry
time frame: Pre-intervention values were recorded at ~9-10 weeks after ACL reconstruction and before the start of the intervention. Post-intervention values were recorded after the 8-week intervention (~18-20 weeks after ACL reconstruction)
description: The knee flexion angle (measured in degrees) during the stance phase was gathered for both limbs using three dimension motion capture and recorded while subjects walked overground. A knee flexion angle symmetry score was computed using the following formula: ensemble average of knee flexion angle of ACL limb minus the ensemble average of knee flexion angle of the non-ACL limb. The mean difference between pre-intervention and post-intervention (post minus pre) knee flexion symmetry scores were calculated for each group. Higher values suggest greater increases in knee flexion angle symmetry from pre-intervention to post-intervention.
measure: Knee Moment Symmetry
time frame: Pre-intervention scores were recorded prior to the start of the intervention and approximately 9-10 weeks after ACL reconstruction. Post-intervention scores were recorded after the 8 week intervention or approximately 18-20 weeks after ACL reconstruction
description: The sagittal plane knee moment (units Nm) during the stance phase was gathered for both limbs using three dimensional motion capture and recorded while subjects walk overground. A symmetry score was computed using the following formula: ensemble average of the knee moment of the ACL limb (Nm) - ensemble average of the knee moment of the non-ACL limb (Nm). The mean difference between pre-intervention and post-intervention knee moment symmetry scores (post minus pre) were calculated for each group. Higher values represent the greater increases in knee moment symmetry from pre-intervention to post-intervention.
arm group label: Functional Resistance Training with a Brace
arm group type: Experimental
description: Participants will receive functional resistance training via a knee brace while walking on a treadmill 2-3 times a week for about 8 weeks.
arm group label: Functional Resistance Training with Elastic Band
arm group type: Experimental
description: Participants will receive functional resistance training via an elastic band attached at the ankle while walking on a treadmill 2-3 times a week for about 8 weeks.
arm group label: Control
arm group type: Sham Comparator
description: Participants will while on a treadmill without an applied resistance 2-3 times a week for about 8 weeks.
intervention type: Other
intervention name: Functional Resistance Training with Brace
description: A brace will be strapped to the leg and apply resistance across the knee while subjects walk on a treadmill.
arm group label: Functional Resistance Training with a Brace
intervention type: Other
intervention name: Control
description: A brace will be strapped to the leg and will not apply resistance across the knee while subjects walk on a treadmill.
arm group label: Control
intervention type: Other
intervention name: Functional Resistance Training with Elastic Band
description: An elastic band will be strapped to the leg and apply resistance across the knee while subjects walk on a treadmill.
arm group label: Functional Resistance Training with Elastic Band
criteria: 
gender: All
minimum age: 14 Years
maximum age: 40 Years
healthy volunteers: No
last name: Riann Palmieri-Smith, PhD
role: Principal Investigator
affiliation: University of Michigan
last name: Chandramouli Krishnan, PhD
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Riann Palmieri-Smith
investigator title: Associate Professor
mesh term: Anterior Cruciate Ligament Injuries
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 