xml: <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/NCT05972876</url>
    </required_header>
    <id_info>
      <org_study_id>NL83376.096.22</org_study_id>
      <nct_id>NCT05972876</nct_id>
    </id_info>
    <brief_title>Graft Maturity After Blood Flow Restriction Training in ACL Reconstruction</brief_title>
    <acronym>TimeToMature</acronym>
    <official_title>MRI-based Graft Maturity After Blood Flow Restriction Training in Bone-patellar Tendon-bone Anterior Cruciate Ligament Reconstruction: a Randomized Controlled Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zuyderland Medisch Centrum</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Zuyderland Medisch Centrum</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>
        Rationale Graft maturity is correlated with strength and biomechanical properties of the&#xD;
        reconstructed ACL. There are concerns that heavy-load resistance training (HLRT) may have&#xD;
        detrimental effects on ACL graft maturation. Therefore, low-load blood flow restriction&#xD;
        training (LL-BFRT) has been suggested as an alternative to HLRT. As LL-BFRT is an&#xD;
        increasingly popular method for the rehabilitation after an ACL reconstruction, it is&#xD;
        important to evaluate the value of this treatment.&#xD;
  &#xD;
        Objectives The main objective is to evaluate the effect of LL-BFRT on MRI-based graft&#xD;
        maturity after ACL reconstruction compared to HLRT. The secondary objectives are the effect&#xD;
        of LL-BFRT on donor-site morbidity, range of motion, knee stability, patient reported outcome&#xD;
        measurements, muscle strength, safe return to pre-injury level of sport and patient&#xD;
        satisfaction. Furthermore, feasibility and safety of rehabilitation will be assessed.&#xD;
  &#xD;
        Study design Randomized controlled trial . Study population Patients who will undergo primary&#xD;
        bone-patellar tendon-bone ACL reconstruction and rehabilitation at Knie-Heup centrum Plus&#xD;
        will be assessed for eligibility. The exclusion criteria are: venous thromboembolism, sickle&#xD;
        cell anemia, severe hypertension, contra-indication for accelerated rehabilitation,&#xD;
        contra-indication for MRI scan or patients who are not willing/able to participate.&#xD;
  &#xD;
        Intervention LL-BFRT includes 12 weeks of biweekly strength training and starts two weeks&#xD;
        after surgery.&#xD;
  &#xD;
        Comparison HLRT includes 12 weeks of biweekly strength training and starts two weeks after&#xD;
        surgery.&#xD;
  &#xD;
        Main study endpoints The main endpoints are MRI-based graft maturity defined as&#xD;
        signal-to-noise quotient three and nine months after surgery.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">September 2027</completion_date>
    <primary_completion_date type="Anticipated">September 2026</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>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Graft Maturity</measure>
      <time_frame>3 and 9 months after surgery</time_frame>
      <description>Graft maturity will me measured as signal intensity of ACL graft using sagittal proton density-weighted images (PDWI)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Range of motion</measure>
      <time_frame>3 and 9 months after surgery</time_frame>
      <description>Range of motion will be evaluated with the use of a goniometer.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Knee stability</measure>
      <time_frame>3 and 9 months after surgery</time_frame>
      <description>With patients lying supine in 30° of flexion anterior tibial translation in mm will be measured with the use of a Rolimeter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anterior knee pain</measure>
      <time_frame>3 and 9 months after surgery</time_frame>
      <description>anterior knee pain is measured on the Numeric Rating Scale, 0=no pain and 10=maximum pain</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Knee pain and function</measure>
      <time_frame>3 and 9 months after surgery</time_frame>
      <description>Knee Osteoarthritis Outcome Score (0 to 100, 0 being the best outcome)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Knee function</measure>
      <time_frame>3 and 9 months after surgery</time_frame>
      <description>knee function (measured using the International Knee Documentation Committee, 0 to 100, 100 being the best outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>patient confidence</measure>
      <time_frame>3 and 9 months after surgery</time_frame>
      <description>using the Anterior Cruciate Ligament Return To Sport after Injury scale, 0 to 100, 100 being the best outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>hamstring strength</measure>
      <time_frame>3 and 9 months after surgery</time_frame>
      <description>Patients hamstring (standing leg curl) strength will be measured on the KINEO LEG PRO</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>isokinetic quadriceps strength</measure>
      <time_frame>3 and 9 months after surgery</time_frame>
      <description>Patients isokinetic quadriceps (seated leg extension) will be measured on the KINEO LEG PRO</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Return to pre-injury level of sport</measure>
      <time_frame>9 months after surgery</time_frame>
      <description>Return to pre-injury level of sport and timing of return to sport will be evaluated by self-report</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">46</enrollment>
    <condition>Anterior Cruciate Ligament Reconstruction</condition>
    <condition>Bone-Patellar Tendon-Bone Grafting</condition>
    <arm_group>
      <arm_group_label>Blood flow restriction training (BFRT)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients in the BFRT group will perform four sets (30, 15, 15 and 15 repetitions, respectively) of unilateral leg press, seated leg extension, deadlift and squat exercises with 30s inter-set rest periods throughout a 0-90° range of motion at 30% one-repetition maximum</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Resistance training (RT)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients in the resistance training group will perform 3x10 reps (30s inter-set rest) of unilateral leg press, seated leg extension, deadlift and squat exercises exercise throughout a 0-90° range of motion with incremental increase in external-load up to 70% of patients' one-repetition maximum</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Blood flow restriction training</intervention_name>
      <description>BFR will be achieved using an automatic personalized tourniquet system (MAD-UP, Angers, France) designed to automatically calculate limb occlusion pressure</description>
      <arm_group_label>Blood flow restriction training (BFRT)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Resistance training</intervention_name>
      <description>Resistance training will be performed without any blood flow restriction</description>
      <arm_group_label>Resistance training (RT)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients (18-64 years) who will undergo primary BPTB reconstruction at Zuyderland&#xD;
               Medical Center and rehabilitation at Knie-Heup centrum Plus.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  venous thromboembolism, sickle cell anemia, severe hypertension, contra-indication for&#xD;
               accelerated rehabilitation, contra-indication for MRI scan or not willing/able to&#xD;
               participate.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jasper Most</last_name>
      <role>Principal Investigator</role>
      <affiliation>Zuyderland Medisch Centrum</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Baris Koc, MD, PhDc</last_name>
      <role>Study Director</role>
      <affiliation>Zuyderland Medisch Centrum</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jasper Most, PhD</last_name>
      <phone>0031625159747</phone>
      <email>j.most@zuyderland.nl</email>
    </overall_contact>
    <location>
      <facility>
        <name>Zuyderland Medical Center</name>
        <address>
          <city>Sittard</city>
          <state>Limburg</state>
          <zip>6162 BG</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Blood Flow Restriction Therapy</keyword>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>Data may be shared upon reasonable written request</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05972876
  org study id: NL83376.096.22
  nct id: NCT05972876
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Rationale Graft maturity is correlated with strength and biomechanical properties of the
        reconstructed ACL. There are concerns that heavy-load resistance training (HLRT) may have
        detrimental effects on ACL graft maturation. Therefore, low-load blood flow restriction
        training (LL-BFRT) has been suggested as an alternative to HLRT. As LL-BFRT is an
        increasingly popular method for the rehabilitation after an ACL reconstruction, it is
        important to evaluate the value of this treatment.
  
        Objectives The main objective is to evaluate the effect of LL-BFRT on MRI-based graft
        maturity after ACL reconstruction compared to HLRT. The secondary objectives are the effect
        of LL-BFRT on donor-site morbidity, range of motion, knee stability, patient reported outcome
        measurements, muscle strength, safe return to pre-injury level of sport and patient
        satisfaction. Furthermore, feasibility and safety of rehabilitation will be assessed.
  
        Study design Randomized controlled trial . Study population Patients who will undergo primary
        bone-patellar tendon-bone ACL reconstruction and rehabilitation at Knie-Heup centrum Plus
        will be assessed for eligibility. The exclusion criteria are: venous thromboembolism, sickle
        cell anemia, severe hypertension, contra-indication for accelerated rehabilitation,
        contra-indication for MRI scan or patients who are not willing/able to participate.
  
        Intervention LL-BFRT includes 12 weeks of biweekly strength training and starts two weeks
        after surgery.
  
        Comparison HLRT includes 12 weeks of biweekly strength training and starts two weeks after
        surgery.
  
        Main study endpoints The main endpoints are MRI-based graft maturity defined as
        signal-to-noise quotient three and nine months after surgery.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: Graft Maturity
  time frame: 3 and 9 months after surgery
  description: Graft maturity will me measured as signal intensity of ACL graft using sagittal proton density-weighted images (PDWI)
  measure: Range of motion
  time frame: 3 and 9 months after surgery
  description: Range of motion will be evaluated with the use of a goniometer.
  measure: Knee stability
  time frame: 3 and 9 months after surgery
  description: With patients lying supine in 30° of flexion anterior tibial translation in mm will be measured with the use of a Rolimeter
  measure: Anterior knee pain
  time frame: 3 and 9 months after surgery
  description: anterior knee pain is measured on the Numeric Rating Scale, 0=no pain and 10=maximum pain
  measure: Knee pain and function
  time frame: 3 and 9 months after surgery
  description: Knee Osteoarthritis Outcome Score (0 to 100, 0 being the best outcome)
  measure: Knee function
  time frame: 3 and 9 months after surgery
  description: knee function (measured using the International Knee Documentation Committee, 0 to 100, 100 being the best outcome
  measure: patient confidence
  time frame: 3 and 9 months after surgery
  description: using the Anterior Cruciate Ligament Return To Sport after Injury scale, 0 to 100, 100 being the best outcome
  measure: hamstring strength
  time frame: 3 and 9 months after surgery
  description: Patients hamstring (standing leg curl) strength will be measured on the KINEO LEG PRO
  measure: isokinetic quadriceps strength
  time frame: 3 and 9 months after surgery
  description: Patients isokinetic quadriceps (seated leg extension) will be measured on the KINEO LEG PRO
  measure: Return to pre-injury level of sport
  time frame: 9 months after surgery
  description: Return to pre-injury level of sport and timing of return to sport will be evaluated by self-report
  arm group label: Blood flow restriction training (BFRT)
  arm group type: Experimental
  description: Patients in the BFRT group will perform four sets (30, 15, 15 and 15 repetitions, respectively) of unilateral leg press, seated leg extension, deadlift and squat exercises with 30s inter-set rest periods throughout a 0-90° range of motion at 30% one-repetition maximum
  arm group label: Resistance training (RT)
  arm group type: Active Comparator
  description: Patients in the resistance training group will perform 3x10 reps (30s inter-set rest) of unilateral leg press, seated leg extension, deadlift and squat exercises exercise throughout a 0-90° range of motion with incremental increase in external-load up to 70% of patients' one-repetition maximum
  intervention type: Behavioral
  intervention name: Blood flow restriction training
  description: BFR will be achieved using an automatic personalized tourniquet system (MAD-UP, Angers, France) designed to automatically calculate limb occlusion pressure
  arm group label: Blood flow restriction training (BFRT)
  intervention type: Behavioral
  intervention name: Resistance training
  description: Resistance training will be performed without any blood flow restriction
  arm group label: Resistance training (RT)
  criteria: 
  gender: All
  gender based: Yes
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Jasper Most
  role: Principal Investigator
  affiliation: Zuyderland Medisch Centrum
  last name: Baris Koc, MD, PhDc
  role: Study Director
  affiliation: Zuyderland Medisch Centrum
  last name: Jasper Most, PhD
  phone: 0031625159747
  email: j.most@zuyderland.nl
  facility: 
  country: Netherlands
  responsible party type: Sponsor
  sharing ipd: Undecided
  ipd description: Data may be shared upon reasonable written request