<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/NCT03016299</url>
  </required_header>
  <id_info>
    <org_study_id>0167-16-MMC</org_study_id>
    <nct_id>NCT03016299</nct_id>
  </id_info>
  <brief_title>The Histological Effect of Various Microfracture Techniques on Human Chondral &amp; Sub-chondral Tissue - an Ex-Vivo Study</brief_title>
  <official_title>The Histological Effect of Various Microfracture Techniques on Human Chondral &amp; Sub-chondral Tissue - an Ex-Vivo Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Meir Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Meir Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The subchondral bone, formed by the subchondral bone plate and the subarticular spongiosa,&#xD;
      plays a key role in supporting the articular cartilage. Marrow stimulation techniques such as&#xD;
      subchondral drilling are clinically important treatment options for symptomatic small&#xD;
      cartilage defects. However, The heat generated from the metal-bone interface during drilling&#xD;
      due to the friction can cause thermal osteonecrosis. , recent clinical evidence suggests that&#xD;
      they may induce alterations in the subchondral bone plate such as intralesional osteophytes,&#xD;
      which persist and may play a role in the degeneration of the repair tissue.&#xD;
&#xD;
      Little is known about whether they induce deleterious changes in the Human Chondral &amp;&#xD;
      Subchondral bone.&#xD;
&#xD;
      The aim of this study was to compare the condral &amp; Sub-chondral Histoligical damage induced&#xD;
      by different drilling techniques.&#xD;
&#xD;
      To the best of our knowledge this is the first time to inspect it, In- Situ, on Human tissue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic articular cartilage defects do not heal spontaneously. However, acute traumatic&#xD;
      osteochondral lesions or surgically inflicted lesions extending into subchondral bone,&#xD;
      spongialization, abrasion or microfracture by drilling causing the release of pluripotent&#xD;
      mesenchymal stem cells from the bone marrow, may heal with repair tissue consisting of&#xD;
      fibrous tissue, fibrocartilage or hyaline-like cartilage. There for Marrow stimulation&#xD;
      techniques as subchondral drilling or microfractures represent ones of the most frequently&#xD;
      used methods for chondral and osteochodral defects repair and considered as standard&#xD;
      techniques. [10-12]&#xD;
&#xD;
      It's well know and logical to understand that the high temperature around the drilling hole&#xD;
      can lead to thermal injury. [1] Temperatures over 47 C degrees for one minutes are associated&#xD;
      thermal osteonecrosis [2,3]. The presence of this necrotic bone may delay healing and&#xD;
      predispose to infection.[1] Many studies evaluate the thermal necrosis of the drill into the&#xD;
      bone [3-6]. In case of osteochondral lesion, drilling of the injury area is the most common&#xD;
      practice in orthopedics surgeries for knee, hip, talus and others. In one study that evaluate&#xD;
      the difference between drilling and microfractures and the impact in the cartilage healing&#xD;
      revealed distinct differences between microfracture and drilling for acute subchondral bone&#xD;
      structure and osteocyte necrosis {4] other study evaluate the healing difference between&#xD;
      drilling and burring in rabbits knee, showing degenerative changes in both technique and&#xD;
      histology longer lived repair the cartilage with 2 mm drilling[5] The main objective of this&#xD;
      study is to evaluate for first time in humans, best to our knowledge, the difference between&#xD;
      drilling with KWires compared to drill in terms of thermal osteonecrosis and&#xD;
      histo-pathological damage.&#xD;
&#xD;
      Methodes:&#xD;
&#xD;
      The specimens will be achieved from 2 groups of patients. The first group correspond to&#xD;
      traumatic subcapital fractures with previous non hip pain complains No osteoarthritis changes&#xD;
      in the x-ray. The second group the specimens achieve from hip arthroplasty surgery due to&#xD;
      osteoarthritic changes.&#xD;
&#xD;
      The femoral head will be obtain during surgery. Drill will be performed in 3 contiguous&#xD;
      areas. First Area by Nailing, Second by KW drilling and 3rd area drilled by regular drill&#xD;
      obtaining a triangle with the three drilled epicenters. All will be tested with 2 different&#xD;
      diameters - 3.5 mm &amp; 1.75mm. All 3 methods will be checked with and without cooling - by&#xD;
      laviation with saline during the drilling/nailing. Temperature measurements using&#xD;
      Thermocouples having 1 mm wire diameter will be used for temperature measurement.&#xD;
&#xD;
      Parameters as Drilling speed, Drilling depth and Orientation to line of sress- trabeculae-&#xD;
      would be uniform.&#xD;
&#xD;
      Histological aspect:&#xD;
&#xD;
      The specimen will be fixed with adequate amount of buffered 4% formalin for 24 to 48 hours&#xD;
      with subsequent gentle decalcification in ethylenediaminetetraacetic acid. Then, the specimen&#xD;
      will be cut with a strong knife/ or scalpel into parallel slices 3 to 5 mm thick and washed&#xD;
      in running water for 12 hours. And after this, the sections from abnormal areas, including&#xD;
      articular surface will be submitted for paraffin embedding.&#xD;
&#xD;
      The histological slides will be stained by hematoxilin-eosin (H&amp;E), PAS, Masson trichrome,&#xD;
      and Alcian blue. The lesions (degeneration, hemorrhage, necrosis and others) will be measured&#xD;
      by micrometer in the microscope.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">July 2017</completion_date>
  <primary_completion_date type="Anticipated">June 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
  </study_design_info>
  <primary_outcome>
    <measure>histological damage</measure>
    <time_frame>withing 48 Hours after specimen fixation</time_frame>
    <description>microscopically assesing the histological damage to Human chondral &amp; Subchondral tissue in 3 common microfractures techniques ( morphological description)</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Partial or Total Hip Arthroplasty</condition>
  <condition>Ex-vivo Preparat of Femoral Head</condition>
  <arm_group>
    <arm_group_label>Osteoarthritis hip joint</arm_group_label>
    <description>specimen of head of femur will be used- after total hip arthroplasty (due to Degenerative Osteoarthritis hip joint )</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Osteoarthritis hip joint</arm_group_label>
    <description>specimen of head of femur will be used- after Hip Hemiarthroplasty -Partial replacment (due to traumatic fracture)</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>microfracture techniques</intervention_name>
    <description>Drill will be performed in 3 contiguous areas. First Area by Nailing, Second by KW drilling and 3rd area drilled by regular drill obtaining a triangle with the three drilled epicenters.</description>
    <arm_group_label>Non-Osteoarthritis hip joint</arm_group_label>
    <arm_group_label>Osteoarthritis hip joint</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        all Adults who went through partial or complete replacement of the hip in our institute&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adults over 18 who agreed to participate in the study and signed an informed consent&#xD;
             form.&#xD;
&#xD;
          -  Patients who went through partial or complete arthroplasty of the hip due to traumatic&#xD;
             or degenerative changes - respectively.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The refusal of the patient to use sampling for any reason, including the desire for&#xD;
             burying the organ / tissue&#xD;
&#xD;
          -  rheumatic - autoimmune diseases that may affect the hip joint (eg: psoriasis,&#xD;
             rheumatoid arthritis, stc')&#xD;
&#xD;
          -  Any chonic medications usage that might affect bone and cartilage (eg: Bifosfantim,&#xD;
             Alendronate, Risedronate, Ibandronate)&#xD;
&#xD;
          -  Any suspected pathology of bone: malignancies, infections, Avascular Necrosis etc'&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>120 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <reference>
    <citation>Alam K. Exploring thermal anisotropy of cortical bone using temperature measurements in drilling. Biomed Mater Eng. 2016 May 12;27(1):39-48. doi: 10.3233/BME-161566.</citation>
    <PMID>27175466</PMID>
  </reference>
  <reference>
    <citation>Augustin G, Davila S, Udilljak T, Staroveski T, Brezak D, Babic S. Temperature changes during cortical bone drilling with a newly designed step drill and an internally cooled drill. Int Orthop. 2012 Jul;36(7):1449-56. doi: 10.1007/s00264-012-1491-z.</citation>
    <PMID>22290154</PMID>
  </reference>
  <reference>
    <citation>Chen H, Hoemann CD, Sun J, Chevrier A, McKee MD, Shive MS, Hurtig M, Buschmann MD. Depth of subchondral perforation influences the outcome of bone marrow stimulation cartilage repair. J Orthop Res. 2011 Aug;29(8):1178-84. doi: 10.1002/jor.21386. Epub 2011 Feb 24.</citation>
    <PMID>21671261</PMID>
  </reference>
  <reference>
    <citation>Chen H, Sun J, Hoemann CD, Lascau-Coman V, Ouyang W, McKee MD, Shive MS, Buschmann MD. Drilling and microfracture lead to different bone structure and necrosis during bone-marrow stimulation for cartilage repair. J Orthop Res. 2009 Nov;27(11):1432-8. doi: 10.1002/jor.20905.</citation>
    <PMID>19402150</PMID>
  </reference>
  <reference>
    <citation>Eriksson AR, Albrektsson T. Temperature threshold levels for heat-induced bone tissue injury: a vital-microscopic study in the rabbit. J Prosthet Dent. 1983 Jul;50(1):101-7. doi: 10.1016/0022-3913(83)90174-9. No abstract available.</citation>
    <PMID>6576145</PMID>
  </reference>
  <reference>
    <citation>Hayashi K, Kumai T, Higashiyama I, Shinohara Y, Matsuda T, Takakura Y. Repair process after fibrocartilaginous enthesis drilling: histological study in a rabbit model. J Orthop Sci. 2009 Jan;14(1):76-84. doi: 10.1007/s00776-008-1284-9. Epub 2009 Feb 13.</citation>
    <PMID>19214692</PMID>
  </reference>
  <reference>
    <citation>Menche DS, Frenkel SR, Blair B, Watnik NF, Toolan BC, Yaghoubian RS, Pitman MI. A comparison of abrasion burr arthroplasty and subchondral drilling in the treatment of full-thickness cartilage lesions in the rabbit. Arthroscopy. 1996 Jun;12(3):280-6. doi: 10.1016/s0749-8063(96)90059-6.</citation>
    <PMID>8783821</PMID>
  </reference>
  <reference>
    <citation>Mohlhenrich SC, Abouridouane M, Heussen N, Holzle F, Klocke F, Modabber A. Thermal evaluation by infrared measurement of implant site preparation between single and gradual drilling in artificial bone blocks of different densities. Int J Oral Maxillofac Surg. 2016 Nov;45(11):1478-1484. doi: 10.1016/j.ijom.2016.05.020. Epub 2016 Jun 11.</citation>
    <PMID>27297835</PMID>
  </reference>
  <reference>
    <citation>Orth P, Goebel L, Wolfram U, Ong MF, Graber S, Kohn D, Cucchiarini M, Ignatius A, Pape D, Madry H. Effect of subchondral drilling on the microarchitecture of subchondral bone: analysis in a large animal model at 6 months. Am J Sports Med. 2012 Apr;40(4):828-36. doi: 10.1177/0363546511430376. Epub 2012 Jan 5.</citation>
    <PMID>22223716</PMID>
  </reference>
  <reference>
    <citation>Singh G, Jain V, Gupta D, Ghai A. Optimization of process parameters for drilled hole quality characteristics during cortical bone drilling using Taguchi method. J Mech Behav Biomed Mater. 2016 Sep;62:355-365. doi: 10.1016/j.jmbbm.2016.05.015. Epub 2016 May 16.</citation>
    <PMID>27254280</PMID>
  </reference>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>January 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>January 8, 2017</last_update_submitted>
  <last_update_submitted_qc>January 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Stress</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03016299
org study id: 0167-16-MMC
nct id: NCT03016299
lead sponsor: 
has dmc: Yes
The subchondral bone, formed by the subchondral bone plate and the subarticular spongiosa,
      plays a key role in supporting the articular cartilage. Marrow stimulation techniques such as
      subchondral drilling are clinically important treatment options for symptomatic small
      cartilage defects. However, The heat generated from the metal-bone interface during drilling
      due to the friction can cause thermal osteonecrosis. , recent clinical evidence suggests that
      they may induce alterations in the subchondral bone plate such as intralesional osteophytes,
      which persist and may play a role in the degeneration of the repair tissue.

      Little is known about whether they induce deleterious changes in the Human Chondral &
      Subchondral bone.

      The aim of this study was to compare the condral & Sub-chondral Histoligical damage induced
      by different drilling techniques.

      To the best of our knowledge this is the first time to inspect it, In- Situ, on Human tissue.
Chronic articular cartilage defects do not heal spontaneously. However, acute traumatic
      osteochondral lesions or surgically inflicted lesions extending into subchondral bone,
      spongialization, abrasion or microfracture by drilling causing the release of pluripotent
      mesenchymal stem cells from the bone marrow, may heal with repair tissue consisting of
      fibrous tissue, fibrocartilage or hyaline-like cartilage. There for Marrow stimulation
      techniques as subchondral drilling or microfractures represent ones of the most frequently
      used methods for chondral and osteochodral defects repair and considered as standard
      techniques. [10-12]

      It's well know and logical to understand that the high temperature around the drilling hole
      can lead to thermal injury. [1] Temperatures over 47 C degrees for one minutes are associated
      thermal osteonecrosis [2,3]. The presence of this necrotic bone may delay healing and
      predispose to infection.[1] Many studies evaluate the thermal necrosis of the drill into the
      bone [3-6]. In case of osteochondral lesion, drilling of the injury area is the most common
      practice in orthopedics surgeries for knee, hip, talus and others. In one study that evaluate
      the difference between drilling and microfractures and the impact in the cartilage healing
      revealed distinct differences between microfracture and drilling for acute subchondral bone
      structure and osteocyte necrosis {4] other study evaluate the healing difference between
      drilling and burring in rabbits knee, showing degenerative changes in both technique and
      histology longer lived repair the cartilage with 2 mm drilling[5] The main objective of this
      study is to evaluate for first time in humans, best to our knowledge, the difference between
      drilling with KWires compared to drill in terms of thermal osteonecrosis and
      histo-pathological damage.

      Methodes:

      The specimens will be achieved from 2 groups of patients. The first group correspond to
      traumatic subcapital fractures with previous non hip pain complains No osteoarthritis changes
      in the x-ray. The second group the specimens achieve from hip arthroplasty surgery due to
      osteoarthritic changes.

      The femoral head will be obtain during surgery. Drill will be performed in 3 contiguous
      areas. First Area by Nailing, Second by KW drilling and 3rd area drilled by regular drill
      obtaining a triangle with the three drilled epicenters. All will be tested with 2 different
      diameters - 3.5 mm & 1.75mm. All 3 methods will be checked with and without cooling - by
      laviation with saline during the drilling/nailing. Temperature measurements using
      Thermocouples having 1 mm wire diameter will be used for temperature measurement.

      Parameters as Drilling speed, Drilling depth and Orientation to line of sress- trabeculae-
      would be uniform.

      Histological aspect:

      The specimen will be fixed with adequate amount of buffered 4% formalin for 24 to 48 hours
      with subsequent gentle decalcification in ethylenediaminetetraacetic acid. Then, the specimen
      will be cut with a strong knife/ or scalpel into parallel slices 3 to 5 mm thick and washed
      in running water for 12 hours. And after this, the sections from abnormal areas, including
      articular surface will be submitted for paraffin embedding.

      The histological slides will be stained by hematoxilin-eosin (H&E), PAS, Masson trichrome,
      and Alcian blue. The lesions (degeneration, hemorrhage, necrosis and others) will be measured
      by micrometer in the microscope.
observational model: Cohort
measure: histological damage
time frame: withing 48 Hours after specimen fixation
description: microscopically assesing the histological damage to Human chondral & Subchondral tissue in 3 common microfractures techniques ( morphological description)
arm group label: Osteoarthritis hip joint
description: specimen of head of femur will be used- after total hip arthroplasty (due to Degenerative Osteoarthritis hip joint )
arm group label: Non-Osteoarthritis hip joint
description: specimen of head of femur will be used- after Hip Hemiarthroplasty -Partial replacment (due to traumatic fracture)
intervention type: Procedure
intervention name: microfracture techniques
description: Drill will be performed in 3 contiguous areas. First Area by Nailing, Second by KW drilling and 3rd area drilled by regular drill obtaining a triangle with the three drilled epicenters.
arm group label: Non-Osteoarthritis hip joint
arm group label: Osteoarthritis hip joint
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 120 Years
healthy volunteers: No
citation: Alam K. Exploring thermal anisotropy of cortical bone using temperature measurements in drilling. Biomed Mater Eng. 2016 May 12;27(1):39-48. doi: 10.3233/BME-161566.
PMID: 27175466
citation: Augustin G, Davila S, Udilljak T, Staroveski T, Brezak D, Babic S. Temperature changes during cortical bone drilling with a newly designed step drill and an internally cooled drill. Int Orthop. 2012 Jul;36(7):1449-56. doi: 10.1007/s00264-012-1491-z.
PMID: 22290154
citation: Chen H, Hoemann CD, Sun J, Chevrier A, McKee MD, Shive MS, Hurtig M, Buschmann MD. Depth of subchondral perforation influences the outcome of bone marrow stimulation cartilage repair. J Orthop Res. 2011 Aug;29(8):1178-84. doi: 10.1002/jor.21386. Epub 2011 Feb 24.
PMID: 21671261
citation: Chen H, Sun J, Hoemann CD, Lascau-Coman V, Ouyang W, McKee MD, Shive MS, Buschmann MD. Drilling and microfracture lead to different bone structure and necrosis during bone-marrow stimulation for cartilage repair. J Orthop Res. 2009 Nov;27(11):1432-8. doi: 10.1002/jor.20905.
PMID: 19402150
citation: Eriksson AR, Albrektsson T. Temperature threshold levels for heat-induced bone tissue injury: a vital-microscopic study in the rabbit. J Prosthet Dent. 1983 Jul;50(1):101-7. doi: 10.1016/0022-3913(83)90174-9. No abstract available.
PMID: 6576145
citation: Hayashi K, Kumai T, Higashiyama I, Shinohara Y, Matsuda T, Takakura Y. Repair process after fibrocartilaginous enthesis drilling: histological study in a rabbit model. J Orthop Sci. 2009 Jan;14(1):76-84. doi: 10.1007/s00776-008-1284-9. Epub 2009 Feb 13.
PMID: 19214692
citation: Menche DS, Frenkel SR, Blair B, Watnik NF, Toolan BC, Yaghoubian RS, Pitman MI. A comparison of abrasion burr arthroplasty and subchondral drilling in the treatment of full-thickness cartilage lesions in the rabbit. Arthroscopy. 1996 Jun;12(3):280-6. doi: 10.1016/s0749-8063(96)90059-6.
PMID: 8783821
citation: Mohlhenrich SC, Abouridouane M, Heussen N, Holzle F, Klocke F, Modabber A. Thermal evaluation by infrared measurement of implant site preparation between single and gradual drilling in artificial bone blocks of different densities. Int J Oral Maxillofac Surg. 2016 Nov;45(11):1478-1484. doi: 10.1016/j.ijom.2016.05.020. Epub 2016 Jun 11.
PMID: 27297835
citation: Orth P, Goebel L, Wolfram U, Ong MF, Graber S, Kohn D, Cucchiarini M, Ignatius A, Pape D, Madry H. Effect of subchondral drilling on the microarchitecture of subchondral bone: analysis in a large animal model at 6 months. Am J Sports Med. 2012 Apr;40(4):828-36. doi: 10.1177/0363546511430376. Epub 2012 Jan 5.
PMID: 22223716
citation: Singh G, Jain V, Gupta D, Ghai A. Optimization of process parameters for drilled hole quality characteristics during cortical bone drilling using Taguchi method. J Mech Behav Biomed Mater. 2016 Sep;62:355-365. doi: 10.1016/j.jmbbm.2016.05.015. Epub 2016 May 16.
PMID: 27254280
responsible party type: Sponsor
mesh term: Fractures, Stress
sharing ipd: No