<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/NCT04402671</url>
  </required_header>
  <id_info>
    <org_study_id>FMD188</org_study_id>
    <nct_id>NCT04402671</nct_id>
  </id_info>
  <brief_title>Lateral Ridge Augmentation Using Cross-linked or Non-cross-linked Collagen Membrane</brief_title>
  <official_title>Lateral Ridge Augmentation Using Cross-linked or Non-cross-linked Collagen Membrane: a Pilot Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Saint-Joseph University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Saint-Joseph University</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of the present trial is to test clinically, radiographically and histologically&#xD;
      , in a lateral alveolar ridge augmentation model (without simultaneous implant placement) the&#xD;
      efficiency in supporting bone formation of a glutaraldehyde cross-linked collagen membrane&#xD;
      compared to a non-cross-linked collagen membrane with the use of a composite&#xD;
      autograft-xenograft mix prepared in a 1:3 ratio&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a pilot one, no sample size calculation has been performed. Random allocation&#xD;
      was done by the sequentially sealed envelope method.&#xD;
&#xD;
      Interventions&#xD;
&#xD;
      Pre-operative preparation:&#xD;
&#xD;
        -  Scaling and root planning and delivering proper hygiene instructions.&#xD;
&#xD;
        -  Fabrication of the occlusal stent/radiographic guide (Silicone impression of the&#xD;
           concerned arch and pouring of the model. Denture teeth are added on the edentulous space&#xD;
           of the cast. A 2 mm thickness clear resin sheet is adapted to the cast with a vacuum&#xD;
           forming machine. The borders of the stent are trimmed with a tungsten carbide bur to&#xD;
           remove the parts that are covering the soft tissues. At the level of the surgical site,&#xD;
           the intaglio of the guide is reduced in a way to prevent any interference with the&#xD;
           swollen soft tissues during the one-week CBCT assessment. In the middle of each denture&#xD;
           tooth, 2 mm cylindrical holes are created occlusally. Gutta-percha is inserted in these&#xD;
           holes to serve as radio-opaque markers and as reference points for per-operative&#xD;
           measurements.&#xD;
&#xD;
        -  Pre-operative Cone Beam CT (CBCTpreop) with the radiographic guide/occlusal stent in the&#xD;
           mouth&#xD;
&#xD;
      Surgical intervention:&#xD;
&#xD;
      Patients are put on an antibiotic regimen consisting of 1 g co-amoxiclav taken twice daily&#xD;
      (Augmentin, GlaxoSmithKline, Brentford, United Kingdom), starting the evening prior to&#xD;
      surgery and continued for 10 days. For patients allergic to penicillins, Clindamycin 300 mg&#xD;
      taken every 6 hours (Dalacin C, Pfeizer, New York City, NY, USA) is prescribed. Before&#xD;
      surgery, the patient is asked to rinse with 0.12% chlorhexidine solution for one minute.&#xD;
      Local anesthesia is delivered using 4% articaine with epinephrine 1:100,000 (Septanest,&#xD;
      Septodont, Saint Maur des Fosses, France). After mid-crestal and vertical releasing incisions&#xD;
      are being made, full thickness flaps are raised. The recipient bone is curetted to remove any&#xD;
      soft tissue that may impede bone healing. Using a ridge mapping caliper, Crestal Bone Width&#xD;
      is recorded at 1 (CBWpreop1), 3 (CBWpreop3) and 5 (CBWpreop5) mm from the crest at the level&#xD;
      of the gutta-percha markers of the guide. Using a periodontal probe, another measure is&#xD;
      recorded from the Ridge Crest to the Border of the Guide (RC-BG). This measure will be used&#xD;
      at the 6-month re-entry to locate the vertical position of the pre-operative ridge mapping&#xD;
      measurements in case of vertical bone changes. On the buccal flaps, superficial periosteal&#xD;
      releasing incisions are performed to release the flap tension and to access the submucosal&#xD;
      tissues. Once accessed, the submucosal tissues are stretched by inserting the wide end of a&#xD;
      periosteal elevator into the incision line and pushing it in a coronal direction, resulting&#xD;
      in flap elongation. In the posterior mandible, the lingual flap is elongated by a lateral&#xD;
      stretching movement using the wide end of the periosteal elevator to separate the sub-mucosal&#xD;
      tissues from the underlying muscle. More anteriorly in the mandible, a superficial periosteal&#xD;
      incision is performed in the lingual flap. The buccal aspect of the crest is decorticated to&#xD;
      ensure vascularization at the recipient site. The particulate bone graft consisting of a&#xD;
      composite autograft-xenograft is then prepared in a 1:3 ratio mixed in sterile saline. A 0.5&#xD;
      cc spoon is used to have an exact 1:3 ratio. The spoon is slightly overfilled, and the excess&#xD;
      is eliminated with a spatula. Only the full spoon content is used in the bone graft mix. The&#xD;
      autograft is obtained by scraping the adjacent bony region with a bone scraper (SafeScraper&#xD;
      TWIST, META, Reggio Emilia, Italy). The xenograft used is an anorganic bovine bone mineral&#xD;
      with a 250-1000 microns particle size (OCS-B Xenomatrix®, Nibec, Chungcheongbuk-do, Korea,&#xD;
      available also under the name of Straumann Xenograft® and Creos Xenogain®). After opening the&#xD;
      sequentially sealed envelope, the patient is allocated to test or control groups. In the test&#xD;
      group a glutaraldehyde cross-linked bovine collagen membrane GCLM is used (RTM Collagen®,&#xD;
      Osteogenics Biomedical, Lubbock, TX, USA), in the control group a non-cross-linked porcine&#xD;
      skin collagen membrane is used (Bioguide, Geistlisch Pharma AG, Wolhusen, Switzerland). The&#xD;
      membrane is fixed first on the buccal side with titanium pins (Masetrpin®, Meisinger, Neuss,&#xD;
      Germany) in a way to create a pouch like space. Second, the composite graft is applied&#xD;
      between the membrane and the crest with a slight over fill. Then the membrane is slightly&#xD;
      stretched, wrapped over the ridge and tightly stabilized palatally/lingually with titanium&#xD;
      pins. The graft-membrane complex should be completely immobile at finger pressure. A tight&#xD;
      wound closure is achieved by placing a first line of horizontal mattress sutures followed by&#xD;
      a second line of interrupted sutures along the horizontal incision. The vertical releasing&#xD;
      incisions are closed with a combination of Laurel-Gottlow sutures and interrupted sutures.&#xD;
      The sutures used are 4(0) PTFE monofilament sutures (Osteogenics Biomedical, Lubbock, TX,&#xD;
      USA). Beside the antibiotic regimen described earlier, all patients are prescribed 0.12%&#xD;
      chlorhexidine mouthwash (twice daily for 2 weeks, starting from the day after surgery),&#xD;
      NSAIDs drugs (Bruffen 400mg every 6 hours, Abbott Laboratories, Illinois, CHI, USA) and/or&#xD;
      paracetamol-opioid analgesics (Solpadeine, Omega Pharma Nazareth, Belgium). An extraoral cold&#xD;
      pressure dressing is applied to minimize postoperative swelling. Sutures are removed 3 weeks&#xD;
      after surgery.&#xD;
&#xD;
      During the first week after surgery, a Cone Beam CT (CBCTpostop) of the operated region is&#xD;
      performed, with the radiographic guide in place.&#xD;
&#xD;
      Follow-up visits will be performed after 1, 3, 6, 10, 14, 18, 22 and 26 weeks.&#xD;
&#xD;
      Re-entry:&#xD;
&#xD;
      At 6 months post-surgery, another Cone Beam CT (CBCTre), with the same radiographic guide in&#xD;
      place, is taken for bone volume assessment and for implant planning. Mid-crestal and vertical&#xD;
      releasing incisions are made. Full thickness flaps are raised, and the pins are removed. Any&#xD;
      non-integrated bone graft material is gently scraped and washed out with saline. The guide is&#xD;
      put in place and using the previously recorded RC-BG measurement to correctly locate the&#xD;
      level of the ridge crest before the ridge augmentation surgery, Crestal Bone Width is&#xD;
      recorded with the ridge mapping caliper at the same locations (CBWre1, CBWre3, CBWre5) taken&#xD;
      during the regeneration surgery. In addition, a UNC-15 periodontal probe is pushed with&#xD;
      pressure against the ridge at a 45 degrees angle at the level of each gutta-percha marker and&#xD;
      at 3 mm form the ridge top. The amount probe penetration in the grafted bone volume is&#xD;
      recorded.&#xD;
&#xD;
      A 2 mm diameter trephine bone biopsy is collected for histomorphometrical and&#xD;
      immunohistochemichal analysis. When possible, the biopsy is extracted horizontally from the&#xD;
      buccal aspect of the ridge at 4 mm from the crest, otherwise it will be collected vertically&#xD;
      from the ridge top. One biopsy is collected per patient, taken where the lateral ridge defect&#xD;
      is the most severe.&#xD;
&#xD;
      Then the implants are inserted, at the prosthetically planned positions, according to the&#xD;
      manufacturer's instructions. Flaps are sutured and a post-operative medication is prescribed&#xD;
      consisting of an antibiotic coverage, an analgesic, and a chlorhexidine mouthwash.&#xD;
&#xD;
      Three months later, the implants are uncovered for abutment connection and will be&#xD;
      subsequently restored.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Actual">August 1, 2020</completion_date>
  <primary_completion_date type="Actual">August 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>
    <intervention_model_description>This study is a pilot randomized clinical trial with parallel groups, with an observation period of 6 - 9 months. It is set to identify the equivalence between the test and the control procedures. An equal randomization is set for the 2 groups</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>The patients are blind to the allocation. The radiographic volumetric changes and the histomorphometrical analysis are assessed by blind examiners.&#xD;
Random allocation was done by the sequentially sealed envelope method. At the time of membrane placement during the surgery, the envelope corresponding to the case sequence number is opened specifying the group allocation.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Linear measurements outcomes</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>the ridge mapping changes in linear measurements between initial ridge width and reentry ridge width at 1, 3 and 5 mm from the ridge crest</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Volumetric measurements outcome</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>Pre-operative Cone Beam CT (CBCTpreop), a Cone Beam CT the first week after surgery (CBCTpostop), and a Cone Beam CT at re-entry post-surgery (CBCTre), with the radiographic guide/occlusal stent in the mouth, are taken.&#xD;
DICOM files from the 3 CBCT scans are uploaded to the BlueSky Plan software (BlueSkyBio, Grayslake, IL, USA) and are superimposed using the gutta-percha markers of the radiographic guide. The Region Of Interest (ROI) is delineated Vpreop, Vpostop and Vre are the volume in cubic millimeters of the ROI measured from the CBCTpreop, CBCTpostop and the CBCTre, respectively.&#xD;
The volumetric outcomes from the DICOM data are used for each group to calculate:&#xD;
the volume of graft resorption.&#xD;
the graft volume created after GBR&#xD;
the bone volume gain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the percentage of graft volume resorption.</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>The percentage of graft volume resorption is calculated by deviding the volume of the graft resorbtion on the volume created after GBR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Linear measurements outcomes on DICOM data</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>On each gutta percha site on the DICOM files these measurements are assessed:&#xD;
Linear measurements in millimeters at 1, 3, 5 mm from the ridge crest in a plane orthogonally bisecting the dental arch at the level of each gutta-percha marker, taken form the ROI of CBCTpreop and CBCTre respectively.&#xD;
The changes of the linear measurements outcomes on DICOM data between CBCTpreop and CBCTre.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Soft tissue healing</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>Soft tissue healing will be assessed during the follow-up visits for the following occurrences Redness and swelling. Wound dehiscence and membrane exposure. Infections or any other unaccounted complications will be recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Periodontal Probe Penetration (PP)</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>PP reflecting the amount of graft maturation is recorded and compared between sites and between patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histology</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>Histology analysis of the bone biopsies taken from the regenerated crests at re-entry surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histomorphometry: percentage of new bone formation</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>Calculation of Percentage new bone formation in the bone biopsies taken from the regenerated crests at re-entry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histomorphometry: percentage of remaining graft particles</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>Calculation of the percentage remaining graft particles in the bone biopsies taken from the regenerated crests at re-entry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histomorphometry: percentage of connective tissue</measure>
    <time_frame>6 - 9 months</time_frame>
    <description>Calculation of the percentage of connective tissue in the bone biopsies taken from the regenerated crests at re-entry</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Bone Loss</condition>
  <arm_group>
    <arm_group_label>non-crosslinked collagen membrane group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 patients (1 male, 1 female)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>glutaraldehyde cross-linked collagen membrane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 patients (2 females)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>non-cross-linked porcine skin collagen membrane</intervention_name>
    <description>non-cross-linked porcine skin collagen membrane used is Bioguide, Geistlisch Pharma AG, Wolhusen, Switzerland.</description>
    <arm_group_label>non-crosslinked collagen membrane group</arm_group_label>
    <other_name>Bioguide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>glutaraldehyde cross-linked bovine collagen membrane</intervention_name>
    <description>glutaraldehyde cross-linked bovine collagen membrane GCLM used is RTM Collagen®, Osteogenics Biomedical, Lubbock, TX, USA.</description>
    <arm_group_label>glutaraldehyde cross-linked collagen membrane</arm_group_label>
    <other_name>Cytoplast RTM</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy patients, non-smokers or smokers&lt;10 cigarettes/day.&#xD;
&#xD;
          -  Age between 20 and 75.&#xD;
&#xD;
          -  Full mouth bleeding score (FmBS) &lt;20 %.&#xD;
&#xD;
          -  Full mouth plaque score (FmPS) &lt;15%.&#xD;
&#xD;
          -  Presence of a residual alveolar ridge with residual bone width &lt; 5 mm and adequate&#xD;
&#xD;
          -  bone height in the maxilla and the mandible.&#xD;
&#xD;
          -  Tooth extraction performed at least 6 weeks before surgery.&#xD;
&#xD;
          -  Presence of enough teeth to support an occlusal stent/radiographic guide.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Systematic diseases.&#xD;
&#xD;
          -  History of radiotherapy in the head and neck region in the last 5 years.&#xD;
&#xD;
          -  Active periodontitis on the remaining teeth.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Allergy to collagen.&#xD;
&#xD;
          -  Intake of medications that may have an effect on bone turnover and mucosal healing&#xD;
             (i.e., tetracycline within the last month, steroids within the last 6 months,&#xD;
             bisphosphonates or fluorides at bone therapeutic levels, vitamin D and metabolites at&#xD;
             therapeutic levels within the last 6 months).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carole F Chakar, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Saint-Joseph University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mario Haddad</name>
      <address>
        <city>Beirut</city>
        <zip>1200</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Lebanon</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>May 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>October 20, 2020</last_update_submitted>
  <last_update_submitted_qc>October 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Saint-Joseph University</investigator_affiliation>
    <investigator_full_name>Mario Haddad</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Guided bone regeneration</keyword>
  <keyword>collagen membrane</keyword>
  <keyword>crosslinked collagen membrane</keyword>
  <keyword>Bone augmentation</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glutaral</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD that underlie results in a publication</ipd_description>
    <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>As soon as the study is published</ipd_time_frame>
    <ipd_access_criteria>A scientific journal</ipd_access_criteria>
  </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/NCT04402671
org study id: FMD188
nct id: NCT04402671
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
The objective of the present trial is to test clinically, radiographically and histologically
      , in a lateral alveolar ridge augmentation model (without simultaneous implant placement) the
      efficiency in supporting bone formation of a glutaraldehyde cross-linked collagen membrane
      compared to a non-cross-linked collagen membrane with the use of a composite
      autograft-xenograft mix prepared in a 1:3 ratio
This study is a pilot one, no sample size calculation has been performed. Random allocation
      was done by the sequentially sealed envelope method.

      Interventions

      Pre-operative preparation:

        -  Scaling and root planning and delivering proper hygiene instructions.

        -  Fabrication of the occlusal stent/radiographic guide (Silicone impression of the
           concerned arch and pouring of the model. Denture teeth are added on the edentulous space
           of the cast. A 2 mm thickness clear resin sheet is adapted to the cast with a vacuum
           forming machine. The borders of the stent are trimmed with a tungsten carbide bur to
           remove the parts that are covering the soft tissues. At the level of the surgical site,
           the intaglio of the guide is reduced in a way to prevent any interference with the
           swollen soft tissues during the one-week CBCT assessment. In the middle of each denture
           tooth, 2 mm cylindrical holes are created occlusally. Gutta-percha is inserted in these
           holes to serve as radio-opaque markers and as reference points for per-operative
           measurements.

        -  Pre-operative Cone Beam CT (CBCTpreop) with the radiographic guide/occlusal stent in the
           mouth

      Surgical intervention:

      Patients are put on an antibiotic regimen consisting of 1 g co-amoxiclav taken twice daily
      (Augmentin, GlaxoSmithKline, Brentford, United Kingdom), starting the evening prior to
      surgery and continued for 10 days. For patients allergic to penicillins, Clindamycin 300 mg
      taken every 6 hours (Dalacin C, Pfeizer, New York City, NY, USA) is prescribed. Before
      surgery, the patient is asked to rinse with 0.12% chlorhexidine solution for one minute.
      Local anesthesia is delivered using 4% articaine with epinephrine 1:100,000 (Septanest,
      Septodont, Saint Maur des Fosses, France). After mid-crestal and vertical releasing incisions
      are being made, full thickness flaps are raised. The recipient bone is curetted to remove any
      soft tissue that may impede bone healing. Using a ridge mapping caliper, Crestal Bone Width
      is recorded at 1 (CBWpreop1), 3 (CBWpreop3) and 5 (CBWpreop5) mm from the crest at the level
      of the gutta-percha markers of the guide. Using a periodontal probe, another measure is
      recorded from the Ridge Crest to the Border of the Guide (RC-BG). This measure will be used
      at the 6-month re-entry to locate the vertical position of the pre-operative ridge mapping
      measurements in case of vertical bone changes. On the buccal flaps, superficial periosteal
      releasing incisions are performed to release the flap tension and to access the submucosal
      tissues. Once accessed, the submucosal tissues are stretched by inserting the wide end of a
      periosteal elevator into the incision line and pushing it in a coronal direction, resulting
      in flap elongation. In the posterior mandible, the lingual flap is elongated by a lateral
      stretching movement using the wide end of the periosteal elevator to separate the sub-mucosal
      tissues from the underlying muscle. More anteriorly in the mandible, a superficial periosteal
      incision is performed in the lingual flap. The buccal aspect of the crest is decorticated to
      ensure vascularization at the recipient site. The particulate bone graft consisting of a
      composite autograft-xenograft is then prepared in a 1:3 ratio mixed in sterile saline. A 0.5
      cc spoon is used to have an exact 1:3 ratio. The spoon is slightly overfilled, and the excess
      is eliminated with a spatula. Only the full spoon content is used in the bone graft mix. The
      autograft is obtained by scraping the adjacent bony region with a bone scraper (SafeScraper
      TWIST, META, Reggio Emilia, Italy). The xenograft used is an anorganic bovine bone mineral
      with a 250-1000 microns particle size (OCS-B Xenomatrix®, Nibec, Chungcheongbuk-do, Korea,
      available also under the name of Straumann Xenograft® and Creos Xenogain®). After opening the
      sequentially sealed envelope, the patient is allocated to test or control groups. In the test
      group a glutaraldehyde cross-linked bovine collagen membrane GCLM is used (RTM Collagen®,
      Osteogenics Biomedical, Lubbock, TX, USA), in the control group a non-cross-linked porcine
      skin collagen membrane is used (Bioguide, Geistlisch Pharma AG, Wolhusen, Switzerland). The
      membrane is fixed first on the buccal side with titanium pins (Masetrpin®, Meisinger, Neuss,
      Germany) in a way to create a pouch like space. Second, the composite graft is applied
      between the membrane and the crest with a slight over fill. Then the membrane is slightly
      stretched, wrapped over the ridge and tightly stabilized palatally/lingually with titanium
      pins. The graft-membrane complex should be completely immobile at finger pressure. A tight
      wound closure is achieved by placing a first line of horizontal mattress sutures followed by
      a second line of interrupted sutures along the horizontal incision. The vertical releasing
      incisions are closed with a combination of Laurel-Gottlow sutures and interrupted sutures.
      The sutures used are 4(0) PTFE monofilament sutures (Osteogenics Biomedical, Lubbock, TX,
      USA). Beside the antibiotic regimen described earlier, all patients are prescribed 0.12%
      chlorhexidine mouthwash (twice daily for 2 weeks, starting from the day after surgery),
      NSAIDs drugs (Bruffen 400mg every 6 hours, Abbott Laboratories, Illinois, CHI, USA) and/or
      paracetamol-opioid analgesics (Solpadeine, Omega Pharma Nazareth, Belgium). An extraoral cold
      pressure dressing is applied to minimize postoperative swelling. Sutures are removed 3 weeks
      after surgery.

      During the first week after surgery, a Cone Beam CT (CBCTpostop) of the operated region is
      performed, with the radiographic guide in place.

      Follow-up visits will be performed after 1, 3, 6, 10, 14, 18, 22 and 26 weeks.

      Re-entry:

      At 6 months post-surgery, another Cone Beam CT (CBCTre), with the same radiographic guide in
      place, is taken for bone volume assessment and for implant planning. Mid-crestal and vertical
      releasing incisions are made. Full thickness flaps are raised, and the pins are removed. Any
      non-integrated bone graft material is gently scraped and washed out with saline. The guide is
      put in place and using the previously recorded RC-BG measurement to correctly locate the
      level of the ridge crest before the ridge augmentation surgery, Crestal Bone Width is
      recorded with the ridge mapping caliper at the same locations (CBWre1, CBWre3, CBWre5) taken
      during the regeneration surgery. In addition, a UNC-15 periodontal probe is pushed with
      pressure against the ridge at a 45 degrees angle at the level of each gutta-percha marker and
      at 3 mm form the ridge top. The amount probe penetration in the grafted bone volume is
      recorded.

      A 2 mm diameter trephine bone biopsy is collected for histomorphometrical and
      immunohistochemichal analysis. When possible, the biopsy is extracted horizontally from the
      buccal aspect of the ridge at 4 mm from the crest, otherwise it will be collected vertically
      from the ridge top. One biopsy is collected per patient, taken where the lateral ridge defect
      is the most severe.

      Then the implants are inserted, at the prosthetically planned positions, according to the
      manufacturer's instructions. Flaps are sutured and a post-operative medication is prescribed
      consisting of an antibiotic coverage, an analgesic, and a chlorhexidine mouthwash.

      Three months later, the implants are uncovered for abutment connection and will be
      subsequently restored.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study is a pilot randomized clinical trial with parallel groups, with an observation period of 6 - 9 months. It is set to identify the equivalence between the test and the control procedures. An equal randomization is set for the 2 groups
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: The patients are blind to the allocation. The radiographic volumetric changes and the histomorphometrical analysis are assessed by blind examiners.
Random allocation was done by the sequentially sealed envelope method. At the time of membrane placement during the surgery, the envelope corresponding to the case sequence number is opened specifying the group allocation.
measure: Linear measurements outcomes
time frame: 6 - 9 months
description: the ridge mapping changes in linear measurements between initial ridge width and reentry ridge width at 1, 3 and 5 mm from the ridge crest
measure: Volumetric measurements outcome
time frame: 6 - 9 months
description: Pre-operative Cone Beam CT (CBCTpreop), a Cone Beam CT the first week after surgery (CBCTpostop), and a Cone Beam CT at re-entry post-surgery (CBCTre), with the radiographic guide/occlusal stent in the mouth, are taken.
DICOM files from the 3 CBCT scans are uploaded to the BlueSky Plan software (BlueSkyBio, Grayslake, IL, USA) and are superimposed using the gutta-percha markers of the radiographic guide. The Region Of Interest (ROI) is delineated Vpreop, Vpostop and Vre are the volume in cubic millimeters of the ROI measured from the CBCTpreop, CBCTpostop and the CBCTre, respectively.
The volumetric outcomes from the DICOM data are used for each group to calculate:
the volume of graft resorption.
the graft volume created after GBR
the bone volume gain.
measure: the percentage of graft volume resorption.
time frame: 6 - 9 months
description: The percentage of graft volume resorption is calculated by deviding the volume of the graft resorbtion on the volume created after GBR
measure: Linear measurements outcomes on DICOM data
time frame: 6 - 9 months
description: On each gutta percha site on the DICOM files these measurements are assessed:
Linear measurements in millimeters at 1, 3, 5 mm from the ridge crest in a plane orthogonally bisecting the dental arch at the level of each gutta-percha marker, taken form the ROI of CBCTpreop and CBCTre respectively.
The changes of the linear measurements outcomes on DICOM data between CBCTpreop and CBCTre.
measure: Soft tissue healing
time frame: 6 - 9 months
description: Soft tissue healing will be assessed during the follow-up visits for the following occurrences Redness and swelling. Wound dehiscence and membrane exposure. Infections or any other unaccounted complications will be recorded
measure: Periodontal Probe Penetration (PP)
time frame: 6 - 9 months
description: PP reflecting the amount of graft maturation is recorded and compared between sites and between patients.
measure: Histology
time frame: 6 - 9 months
description: Histology analysis of the bone biopsies taken from the regenerated crests at re-entry surgery
measure: Histomorphometry: percentage of new bone formation
time frame: 6 - 9 months
description: Calculation of Percentage new bone formation in the bone biopsies taken from the regenerated crests at re-entry
measure: Histomorphometry: percentage of remaining graft particles
time frame: 6 - 9 months
description: Calculation of the percentage remaining graft particles in the bone biopsies taken from the regenerated crests at re-entry
measure: Histomorphometry: percentage of connective tissue
time frame: 6 - 9 months
description: Calculation of the percentage of connective tissue in the bone biopsies taken from the regenerated crests at re-entry
arm group label: non-crosslinked collagen membrane group
arm group type: Active Comparator
description: 2 patients (1 male, 1 female)
arm group label: glutaraldehyde cross-linked collagen membrane
arm group type: Active Comparator
description: 2 patients (2 females)
intervention type: Other
intervention name: non-cross-linked porcine skin collagen membrane
description: non-cross-linked porcine skin collagen membrane used is Bioguide, Geistlisch Pharma AG, Wolhusen, Switzerland.
arm group label: non-crosslinked collagen membrane group
other name: Bioguide
intervention type: Other
intervention name: glutaraldehyde cross-linked bovine collagen membrane
description: glutaraldehyde cross-linked bovine collagen membrane GCLM used is RTM Collagen®, Osteogenics Biomedical, Lubbock, TX, USA.
arm group label: glutaraldehyde cross-linked collagen membrane
other name: Cytoplast RTM
criteria: 
gender: All
minimum age: 20 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Carole F Chakar, PhD
role: Study Director
affiliation: Saint-Joseph University
facility: 
country: Lebanon
responsible party type: Principal Investigator
investigator affiliation: Saint-Joseph University
investigator full name: Mario Haddad
investigator title: Principal Investigator
mesh term: Glutaral
sharing ipd: Yes
ipd description: All IPD that underlie results in a publication
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: As soon as the study is published
ipd access criteria: A scientific journal