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/NCT05983692</url>
    </required_header>
    <id_info>
      <org_study_id>2021.654</org_study_id>
      <nct_id>NCT05983692</nct_id>
    </id_info>
    <brief_title>MZG Wire for Augmentation of ACL Reconstruction</brief_title>
    <official_title>The Clinical Translation of a Biodegradable Magnesium Zinc Gadolinium Wire Developed for Augmentation of ACL Reconstruction, From Benchside to Bedside</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chinese University of Hong Kong</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Chinese University of Hong Kong</source>
    <oversight_info>
      <has_dmc>Yes</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>
        Anterior Cruciate Ligament Reconstruction (ACLR) is the standard treatment of ACL injury. The&#xD;
        most common grafts used for ACLR are autografts such as hamstring tendon graft. As this&#xD;
        process requires the healing of two inhomogeneous tissues -bone with tendon, ACLR can be&#xD;
        compromised by poor self-healing response. The use of biodegradable materials as implants to&#xD;
        stimulate healing has been developed in orthopaedics for decades. In the ACLR model, our team&#xD;
        and others reported that Mg based interference screw could consistently enhance ACLR by&#xD;
        upregulating the expression of osteogenic and angiogenic factors experimentally. To improve&#xD;
        on the potential insufficient mechanical strength of Mg-based screws in clinical&#xD;
        applications, the investigators have developed a magnesium-zinc-gadolinium (MZG) alloy wire&#xD;
        as a suture for braiding the tendon graft, following the standard procedure in our centre for&#xD;
        the preparation of graft during ACLR. In a validated rabbit model, previous research found&#xD;
        the MZG alloy wire showed good formability in material tests when being used as braiding&#xD;
        suture, accompanied with the accelerated tunnel healing as shown by significantly more bone&#xD;
        formation, and histologically with more regeneration of fibrocartilages at bone tendon&#xD;
        healing interface. To further determine its efficacy and safety, MZG wire was tested in&#xD;
        comparison with conventional suture in 16 goats as our pilot study. Radiological analysis of&#xD;
        the femoral bone tunnel showed the bone volume fraction was significantly higher in MZG alloy&#xD;
        wire group, with no significant difference seen in the safety tests.&#xD;
  &#xD;
        To determine whether the MZG alloy wire and its degradation over time after ACLR can promote&#xD;
        graft healing and promote functional recovery in patients, the investigators propose to&#xD;
        investigate the effect of using MZG alloy wire as a braiding suture in ACLR in a randomized&#xD;
        controlled trial, with 30 patients in the intervention group using MZG alloy wire and 30 in&#xD;
        the control group using conventional suture.&#xD;
  &#xD;
        As a direct measurement, High Resolution Peripheral Quantitative Computed Tomography&#xD;
        (HR-pQCT) will be used to measure the microarchitecture in the bone shell tunnel. This novel&#xD;
        use of MZG alloy wire as a braiding suture in ACLR, which is a standard procedure for the&#xD;
        preparation of graft, that is not related to the fixation of the graft. This can incorporate&#xD;
        the benefit of an Mg-based component for its degradation in vivo and release of osteogenic&#xD;
        and angiogenic by-products, but without the risk of compromising the fixation of the tendon&#xD;
        graft and without the need for additional steps during surgery.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2026</completion_date>
    <primary_completion_date type="Anticipated">September 2025</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>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Bone shell size</measure>
      <time_frame>2 weeks and 3, 6, 12 and 24 months post-operation.</time_frame>
      <description>HR-pQCT (ExtremCT II, Scanco, Switzerland) will be used to measure the bone shell size at graft tunnel interface. The involved knees will be investigated. A total of 1344 axial slices with an image matrix of 2304 × 2304 were collected at a nominal isotropic voxel size of 60.7μm. The scan region was defined by the scout view image acquired in the sagittal plane.The total scanning length was 81.6mm which covered the tunnel from proximal tibia to distal femoral condyle (X-ray settings: 68kVp, 1470μA, 100ms integration time, 156mAs per stack (168 slices).Image segmentation will be performed to select the bone shell features at graft tunnel interfaces near femoral and tibial intra-articular apertures with standardized threshold values at a thickness of ~2.5 mm (40 slices). Geometric transformation will be performed to adjust for the variations in angle between scanning axis and tunnel axis by a cosine function.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>International Knee Documentation Committee</measure>
      <time_frame>Pre-operation, 2 weeks and 3, 6, 12 and 24 months post-operation.</time_frame>
      <description>Consists of 10 questions on symptoms and activity ranging from 0 to 100 where 100 implies perfect knee function.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tegner activity score</measure>
      <time_frame>Pre-operation, 2 weeks and 3, 6, 12 and 24 months post-operation.</time_frame>
      <description>This is an activity level scaled from 1 (low activity) to 10 (high activity).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Passive Knee laxity</measure>
      <time_frame>3, 6, 12 and 24 months post-operation.</time_frame>
      <description>To measure anterior-posterior knee laxity, the KT-1000 knee ligament arthrometer (MEDmetric Corp, San Diego, CA, USA) will be used. A manual force test will be applied until a 30lb sound signal is activated. Three trials will be performed. A side difference of 3 mm above is considered clinically relevant.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Isokinetic muscle strength</measure>
      <time_frame>3, 6, 12 and 24 months post-operation</time_frame>
      <description>The dynamometer (Biodex System 4, Biodex Medical Systems Inc., New York, USA) will be used for measuring Isokinetic muscle strength in N. Subjects will perform a standardized warm-up exercise (5 min cycling) followed by the test. Concentric/concentric contractions of knee extension/flexion will be tested at 60°/s and 180°/s. Subjects will be seated on the dynamometer chair with their hips flexed to 85°.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum myokine evaluation</measure>
      <time_frame>Pre-operation, Day 1, 2 and 6 weeks and 3 months post-operation</time_frame>
      <description>To evaluate the safety of MZG alloy wire with respect to inflammatory responses, 5 ml blood samples will be collected for C-reactive protein measurement using ELISA kit.&#xD;
  Measurements of Ca, Mg, P, Cr, Urea, ALT, AST, TP, ALB, GLB will be taken to monitorpotential effect of the MZG alloy wire. The blood tests will be performed at baseline, day 1 post-op, 2 weeks, 6 weeks and 12 weeks post-op, since the degradation of MZG wire is faster based on our preclinical study results.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Single leg hop distance</measure>
      <time_frame>6, 12 and 24 months post-operation</time_frame>
      <description>The average of single leg hop distance in cm with three attempts will be measured during the single leg hop test.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Anterior Cruciate Ligament Rupture</condition>
    <arm_group>
      <arm_group_label>MZG Wire group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Intervention: Magnesium Zinc Gadolinium (MZG) wire as braiding suture to braid the tendon graft.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>control group</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>2-0 vicryl suture as control, size and length matched MZG alloy wire</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Magnesium Zinc Gadolinium alloy wire</intervention_name>
      <description>MZG wire will be used as a braiding suture to braid tendon graft, which is a standard preparation of graft and is not related to fixation of the tendon graft</description>
      <arm_group_label>MZG Wire group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 18-40&#xD;
  &#xD;
            -  Unilateral ACL tear for primary ACLR (Single bundle, Hamstring) confirmed clinically&#xD;
               and radiologically.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Concomitant multiple ligament injuries requiring additional surgical procedures,&#xD;
  &#xD;
            -  Preoperative radiographic signs of arthritis,&#xD;
  &#xD;
            -  Revision ACLR&#xD;
  &#xD;
            -  Femoral tunnel interference screws&#xD;
  &#xD;
            -  Contralateral knee with ACL deficiency or reconstruction&#xD;
  &#xD;
            -  Medical co-morbidities&#xD;
  &#xD;
            -  Long-term steroid intake&#xD;
  &#xD;
            -  Non-compliance to our rehabilitation protocol.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>40 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Michael Tim-Yun Ong</last_name>
      <phone>055699059</phone>
      <email>michael.ong@cuhk.edu.hk</email>
    </overall_contact>
    <location>
      <facility>
        <name>The Chinese University of Hong Kong</name>
        <address>
          <city>Hong Kong</city>
          <country>Hong Kong</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Hong Kong</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Chinese University of Hong Kong</investigator_affiliation>
      <investigator_full_name>Prof. Tim-Yun Michael ONG</investigator_full_name>
      <investigator_title>Clinical Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>ACLR</keyword>
    <keyword>MZG wire</keyword>
    <keyword>Bone tendon interface healing</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Rupture</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>starting 6 months after publication</ipd_time_frame>
      <ipd_access_criteria>Journal reviewers</ipd_access_criteria>
    </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/NCT05983692
  org study id: 2021.654
  nct id: NCT05983692
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Anterior Cruciate Ligament Reconstruction (ACLR) is the standard treatment of ACL injury. The
        most common grafts used for ACLR are autografts such as hamstring tendon graft. As this
        process requires the healing of two inhomogeneous tissues -bone with tendon, ACLR can be
        compromised by poor self-healing response. The use of biodegradable materials as implants to
        stimulate healing has been developed in orthopaedics for decades. In the ACLR model, our team
        and others reported that Mg based interference screw could consistently enhance ACLR by
        upregulating the expression of osteogenic and angiogenic factors experimentally. To improve
        on the potential insufficient mechanical strength of Mg-based screws in clinical
        applications, the investigators have developed a magnesium-zinc-gadolinium (MZG) alloy wire
        as a suture for braiding the tendon graft, following the standard procedure in our centre for
        the preparation of graft during ACLR. In a validated rabbit model, previous research found
        the MZG alloy wire showed good formability in material tests when being used as braiding
        suture, accompanied with the accelerated tunnel healing as shown by significantly more bone
        formation, and histologically with more regeneration of fibrocartilages at bone tendon
        healing interface. To further determine its efficacy and safety, MZG wire was tested in
        comparison with conventional suture in 16 goats as our pilot study. Radiological analysis of
        the femoral bone tunnel showed the bone volume fraction was significantly higher in MZG alloy
        wire group, with no significant difference seen in the safety tests.
  
        To determine whether the MZG alloy wire and its degradation over time after ACLR can promote
        graft healing and promote functional recovery in patients, the investigators propose to
        investigate the effect of using MZG alloy wire as a braiding suture in ACLR in a randomized
        controlled trial, with 30 patients in the intervention group using MZG alloy wire and 30 in
        the control group using conventional suture.
  
        As a direct measurement, High Resolution Peripheral Quantitative Computed Tomography
        (HR-pQCT) will be used to measure the microarchitecture in the bone shell tunnel. This novel
        use of MZG alloy wire as a braiding suture in ACLR, which is a standard procedure for the
        preparation of graft, that is not related to the fixation of the graft. This can incorporate
        the benefit of an Mg-based component for its degradation in vivo and release of osteogenic
        and angiogenic by-products, but without the risk of compromising the fixation of the tendon
        graft and without the need for additional steps during surgery.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Outcomes Assessor)
  measure: Bone shell size
  time frame: 2 weeks and 3, 6, 12 and 24 months post-operation.
  description: HR-pQCT (ExtremCT II, Scanco, Switzerland) will be used to measure the bone shell size at graft tunnel interface. The involved knees will be investigated. A total of 1344 axial slices with an image matrix of 2304 × 2304 were collected at a nominal isotropic voxel size of 60.7μm. The scan region was defined by the scout view image acquired in the sagittal plane.The total scanning length was 81.6mm which covered the tunnel from proximal tibia to distal femoral condyle (X-ray settings: 68kVp, 1470μA, 100ms integration time, 156mAs per stack (168 slices).Image segmentation will be performed to select the bone shell features at graft tunnel interfaces near femoral and tibial intra-articular apertures with standardized threshold values at a thickness of ~2.5 mm (40 slices). Geometric transformation will be performed to adjust for the variations in angle between scanning axis and tunnel axis by a cosine function.
  measure: International Knee Documentation Committee
  time frame: Pre-operation, 2 weeks and 3, 6, 12 and 24 months post-operation.
  description: Consists of 10 questions on symptoms and activity ranging from 0 to 100 where 100 implies perfect knee function.
  measure: Tegner activity score
  time frame: Pre-operation, 2 weeks and 3, 6, 12 and 24 months post-operation.
  description: This is an activity level scaled from 1 (low activity) to 10 (high activity).
  measure: Passive Knee laxity
  time frame: 3, 6, 12 and 24 months post-operation.
  description: To measure anterior-posterior knee laxity, the KT-1000 knee ligament arthrometer (MEDmetric Corp, San Diego, CA, USA) will be used. A manual force test will be applied until a 30lb sound signal is activated. Three trials will be performed. A side difference of 3 mm above is considered clinically relevant.
  measure: Isokinetic muscle strength
  time frame: 3, 6, 12 and 24 months post-operation
  description: The dynamometer (Biodex System 4, Biodex Medical Systems Inc., New York, USA) will be used for measuring Isokinetic muscle strength in N. Subjects will perform a standardized warm-up exercise (5 min cycling) followed by the test. Concentric/concentric contractions of knee extension/flexion will be tested at 60°/s and 180°/s. Subjects will be seated on the dynamometer chair with their hips flexed to 85°.
  measure: Serum myokine evaluation
  time frame: Pre-operation, Day 1, 2 and 6 weeks and 3 months post-operation
  description: To evaluate the safety of MZG alloy wire with respect to inflammatory responses, 5 ml blood samples will be collected for C-reactive protein measurement using ELISA kit.
  Measurements of Ca, Mg, P, Cr, Urea, ALT, AST, TP, ALB, GLB will be taken to monitorpotential effect of the MZG alloy wire. The blood tests will be performed at baseline, day 1 post-op, 2 weeks, 6 weeks and 12 weeks post-op, since the degradation of MZG wire is faster based on our preclinical study results.
  measure: Single leg hop distance
  time frame: 6, 12 and 24 months post-operation
  description: The average of single leg hop distance in cm with three attempts will be measured during the single leg hop test.
  arm group label: MZG Wire group
  arm group type: Experimental
  description: Intervention: Magnesium Zinc Gadolinium (MZG) wire as braiding suture to braid the tendon graft.
  arm group label: control group
  arm group type: No Intervention
  description: 2-0 vicryl suture as control, size and length matched MZG alloy wire
  intervention type: Device
  intervention name: Magnesium Zinc Gadolinium alloy wire
  description: MZG wire will be used as a braiding suture to braid tendon graft, which is a standard preparation of graft and is not related to fixation of the tendon graft
  arm group label: MZG Wire group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 40 Years
  healthy volunteers: No
  last name: Michael Tim-Yun Ong
  phone: 055699059
  email: michael.ong@cuhk.edu.hk
  facility: 
  country: Hong Kong
  responsible party type: Principal Investigator
  investigator affiliation: Chinese University of Hong Kong
  investigator full name: Prof. Tim-Yun Michael ONG
  investigator title: Clinical Assistant Professor
  mesh term: Rupture
  sharing ipd: Yes
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd info type: Analytic Code
  ipd time frame: starting 6 months after publication
  ipd access criteria: Journal reviewers