<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/NCT03239275</url>
  </required_header>
  <id_info>
    <org_study_id>ORD14-1D</org_study_id>
    <nct_id>NCT03239275</nct_id>
  </id_info>
  <brief_title>Clinical Evaluation of Bio-creative Therapy for En Masse Retraction of the Maxillary Anterior Teeth</brief_title>
  <official_title>Evaluation of Labial Versus Lingual Biocreative Therapy for en Masse Retraction of Maxillary Anterior Teeth: A Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ain Shams University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ain Shams University</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>
      The purpose of this study is to compare the effectiveness and efficiency of labial versus&#xD;
      lingual biocreative therapy in achieving en masse retraction of the maxillary anterior teeth&#xD;
      in subjects with class II malocclusion requiring upper first premolar extraction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Background:&#xD;
&#xD;
           Maximum anchorage is commonly required in patients with severe protrusion. Conventional&#xD;
           retraction by sliding mechanics in extraction cases have been associated with variable&#xD;
           degrees of anchorage loss. Use of miniscrew for reinforcement of orthodontic anchorage&#xD;
           has become increasingly popular in recent years. Miniscrews are convenient, save time,&#xD;
           and do not require patient cooperation. However, sliding mechanics with direct anchorage&#xD;
           from mini-screw can have several biomechanical drawbacks. The force used during&#xD;
           retraction is not reciprocal, posteriorly it is negated by the miniscrew, not by teeth.&#xD;
           As a result, either the entire arch or the anterior segment rotates around the center of&#xD;
           resistance. These mechanics produce posterior open bite and anterior deep overbite. To&#xD;
           avoid this problem, Chung et al, introduced the technique that minimizes side effects by&#xD;
           replacing the posterior appliance segments with the partially osteointegrated C-implant.&#xD;
           This system was called &quot;biocreative therapy&quot;.&#xD;
&#xD;
           With the bio-creative approach, true intrusion vectors on the anterior teeth can be&#xD;
           applied without unwanted reactive forces affecting the posterior teeth, the posterior&#xD;
           teeth are left intact.&#xD;
&#xD;
           In Labial biocreative therapy type I, a 0.016 × 0.022-in stainless steel utility&#xD;
           archwire is placed from the anterior segment into the implant tube, and gable bends are&#xD;
           used to generate an anterior torque moment on the anterior segment of the teeth to&#xD;
           provide bodily movement during en-masse retraction. On the other hand, in biocreative&#xD;
           therapy type II, en masse anterior retraction is accomplished by applying retraction&#xD;
           force via NiTi coil springs between an anterior retraction hook placed between the&#xD;
           lateral incisor and the canine and the skeletal anchorage. An overlay intrusion arch&#xD;
           wire is used to generate torque on the anterior segment of teeth; thereby various&#xD;
           patterns of tooth movement can be obtained through the combination of intrusion force,&#xD;
           retraction force, and length of the retraction hook. Location and management of the&#xD;
           center of resistance (Cres) with respect to retraction force vectors is critical. The&#xD;
           clinician should select the length of a power arm according to the desired type of tooth&#xD;
           movement; controlled lingual crown tipping, root tipping, or bodily movement.&#xD;
&#xD;
           Adult orthodontics is an increasing part of the orthodontic practice. However, adult&#xD;
           patients are often annoyed by the appearance of labial brackets and tend to delay or&#xD;
           avoid starting orthodontic treatment. Lingual orthodontics is a viable option for these&#xD;
           patients as being &quot;invisible orthodontic treatment&quot;. The disadvantages of lingual&#xD;
           orthodontics include the excessive chair time, complicated bio-mechanics, patient&#xD;
           discomfort, expensive lab procedures, and high material prices. However, several&#xD;
           innovations have improved the use of lingual orthodontics, such as customized lingual&#xD;
           brackets and two-dimensional lingual brackets that can be bonded directly. Nonetheless,&#xD;
           the efficient control of anterior torque and intrusion during retraction continues to be&#xD;
           a limiting challenge.&#xD;
&#xD;
           Mini-implants placed on each side of the palate have been used in conjunction with&#xD;
           lingual orthodontics to avoid uncontrolled tipping and the deepening of the anterior&#xD;
           bite during en masse retraction. A lever arm is soldered to the main lingual arch wire.&#xD;
           This moves the force vector apically and closer to the center of resistance, thereby&#xD;
           allowing better control of torque during retraction. However, play within the slot&#xD;
           allows some of the torque to be lost during retraction. In addition, unwanted canting of&#xD;
           the occlusal plane may occur if bilateral mini-implants are not in the same horizontal&#xD;
           plane, due to different force vectors generated during retraction. Moreover, the sliding&#xD;
           mechanics may be adversely affected by friction within bracket slots and tubes, causing&#xD;
           unwanted distalization of posterior teeth.&#xD;
&#xD;
           Lingual Biocreative therapy for anterior retraction offers several advantages. En masse&#xD;
           retraction of the maxillary anterior dentition is achieved using C-lingual retractor and&#xD;
           C-palatal plate. The C-lingual retractor is bonded to the lingual surfaces of the upper&#xD;
           six anteriors, providing excellent esthetics. The C-palatal plate is fixed near the&#xD;
           median palatal suture with mini-implants. The upper posterior orthodontic appliances are&#xD;
           not needed as anchorage for 3-dimensional retraction of the upper anteriors.&#xD;
&#xD;
           Lingual biocreative therapy technique can be used to provide patients with esthetic&#xD;
           treatment, excellent anchorage control offered by skeletal anchorage, rapid and&#xD;
           controlled retraction, simplified orthodontic bio-mechanics, and avoiding unnecessary&#xD;
           use of complex orthodontic devices. Posterior teeth are not disturbed by friction in the&#xD;
           appliance.&#xD;
&#xD;
           As the majority of research work related to biocreative therapy technique was mainly&#xD;
           case reports, three-dimensional finite element analyses, and three retrospective studies&#xD;
           using two-dimensional cephalometric data, and the fact that no studies; up to the time&#xD;
           of this writing; compared the labial and lingual biocreative techniques, the idea of&#xD;
           this study has aroused as to use the advanced technology of three-dimensional imaging to&#xD;
           clinically evaluate and compare the effects of labial and lingual biocreative therapy&#xD;
           for en masse retraction of the maxillary anterior teeth.&#xD;
&#xD;
        2. Research Hypothesis:&#xD;
&#xD;
           The null hypothesis (H0) of this research is that there will be no statistically&#xD;
           significant differences between labial and lingual biocreative therapy in the mean&#xD;
           change in the upper incisor inclination after en masse retraction of the anterior teeth&#xD;
           in subjects with class II malocclusion requiring upper first premolar extraction.&#xD;
&#xD;
        3. Objectives:&#xD;
&#xD;
           The primary objective of this study is to determine if there will be statistically&#xD;
           significant differences between labial and lingual biocreative therapy in the mean&#xD;
           change in the upper incisor inclination after en masse retraction of the anterior teeth.&#xD;
&#xD;
           Secondary objectives include:&#xD;
&#xD;
           To compare between labial and lingual biocreative therapy regarding:&#xD;
&#xD;
             -  Changes in the soft tissue parameters including the nasolabial angle, inter-labial&#xD;
                gap, and position of the upper and lower lips in the antero-posterior dimension;&#xD;
                that would contribute to soft tissue profile correction.&#xD;
&#xD;
             -  Molar anchorage loss.&#xD;
&#xD;
             -  Patient satisfaction from treatment with either the labial or lingual biocreative&#xD;
                therapy.&#xD;
&#xD;
             -  Vertical movement of the crown of the six maxillary anterior teeth.&#xD;
&#xD;
             -  Changes in the transverse dimension of the upper arch.&#xD;
&#xD;
             -  Skeletal measurements including the mean change in the position of point A from the&#xD;
                Nasion perpendicular plane and change in the SNA angle.&#xD;
&#xD;
             -  Time duration required to complete the retraction phase.&#xD;
&#xD;
        4. Study design According to the norms of the CONSORT STATEMENT, this study will be&#xD;
           clinical with intervention, in which the allocation of the subjects will be randomized&#xD;
           (block randomization). This study will be parallel with blinding for the outcome&#xD;
           assessors. The primary purpose of this study will be treatment.&#xD;
&#xD;
        5. Participants - Settings and locations where the data are collected The treatment will be&#xD;
           performed in the outpatient clinics of Department of Orthodontics of Ain Shams&#xD;
           University. This public university predominantly serves low-income population living in&#xD;
           Cairo, Egypt. Data will be collected from January 2016 through November 2017.&#xD;
&#xD;
        6. Interventions Two groups will receive treatment. Group 1 will be treated with the labial&#xD;
           biocreative therapy group until the achievement of normal overjet (1 to 3 mm).&#xD;
&#xD;
      Group 2 will be treated with lingual biocreative therapy group until the achievement of&#xD;
      normal overjet (1 to 3 mm).&#xD;
&#xD;
      7a. Sample size Sample size calculation was based on the studies by Kim et al and Kim et al.&#xD;
      For the labial group, a mean change in the upper incisor inclination to SN plane of 15.33&#xD;
      degrees, with a standard deviation of 6.85 was reported by Kim et al who compared&#xD;
      pre-treatment cephalometric radiographs with those taken after en-masse retraction of the 6&#xD;
      anterior teeth using temporary skeletal anchorage devices as the exclusive source of&#xD;
      anchorage. No brackets or bands were placed on the posterior dentition during retraction.&#xD;
      Regarding the lingual group, the mean change in the upper incisor inclination to SN plane of&#xD;
      7.8 degrees, with a standard deviation of 5.5 was reported by Kim et al who compared&#xD;
      pre-treatment cephalometric radiographs with those taken after en-masse retraction of the 6&#xD;
      anterior teeth using the lingual biocreative therapy technique.&#xD;
&#xD;
      The effect size ratio was calculated to be 1.212 using G*power software (Universität&#xD;
      Düsseldorf, Germany). A t-test assuming equal variance for two independent groups was used&#xD;
      and the power was set as 0.8, allocation ratio of 1:1 and the Type I error probability&#xD;
      (alpha) associated with this test was set as 0.05. Results of the test showed that &quot;the group&#xD;
      sample sizes of 12 each would achieve 80.09% power to reject the null hypothesis of equal&#xD;
      means with a significance level (alpha) of 0.05 using a two-sided two-sample equal variance&#xD;
      t-test&quot;.&#xD;
&#xD;
      Therefore, 24 subjects will be needed, with 12 subjects in each group. To account for patient&#xD;
      loss to follow up (attrition), a sample size of 30 patients will be selected and divided into&#xD;
      two groups, fifteen each.&#xD;
&#xD;
      7b. Interim analysis and stopping guidelines In both groups, in case of mobility in the&#xD;
      skeletal anchorage device used in any subject, the load will be removed for about two weeks&#xD;
      and oral hygiene instructions will be reinforced. After that, the load will be restored. If&#xD;
      the mobility persists, surgical exposure of the skeletal anchorage device will be done and&#xD;
      either insertion of longer mini screws or a change in the position of the skeletal anchorage&#xD;
      device will be done.&#xD;
&#xD;
      Any harms, adverse effects or unintended effects of the study intervention will be documented&#xD;
      and reported. Post-surgical swelling and pain are anticipated and will be addressed by&#xD;
      antibiotics and pain killers. Other unanticipated surgical harms have to be immediately&#xD;
      managed and will be reported. Harms related to the orthodontic appliances will be managed by&#xD;
      the principal investigator.&#xD;
&#xD;
      8. Randomization 8a. Sequence generation The randomization of the recruited subjects will be&#xD;
      done with a randomized list, using random.org website. This list is made by an individual not&#xD;
      involved in the clinical trial (A.Z.) 8b. Type The type of randomization will be block&#xD;
      randomization. The number of blocks and block size will be blinded to the investigators.&#xD;
&#xD;
      9. Allocation and concealment mechanism&#xD;
&#xD;
        -  Each patient will be allocated a number from sequentially numbered opaque sealed&#xD;
           envelopes after fulfilment of the inclusion criteria and signing the informed consent to&#xD;
           be enrolled in the study.&#xD;
&#xD;
        -  According to the number, the patients will be then allocated into one of the groups&#xD;
           using a randomization table.&#xD;
&#xD;
           10. Implementation Before the beginning of the research, the allocation sequence will be&#xD;
           generated by a person not involved in the study (Dr A.Z.). The random list will be&#xD;
           sealed from the principal investigator who will enrol participants. After the&#xD;
           participant takes a sealed number, A.Z. will be contacted to implement the allocation.&#xD;
           All the study contributors will have no access to the random list. The envelopes will be&#xD;
           closed with the type of treatment selected for storage of the information.&#xD;
&#xD;
           11. Blinding Blinding will be carried out only for the data assessment because the&#xD;
           researchers, participants and subjects can not be blinded. Therefore, a person who does&#xD;
           not know the nature of the trial will analyze the data.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 17, 2016</start_date>
  <completion_date type="Actual">September 30, 2018</completion_date>
  <primary_completion_date type="Actual">April 30, 2018</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>Type of anterior tooth movement.</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>This would be detected by measurement of the mean change in bucco-lingual inclination of every anterior tooth from the baseline. This outcome will be measured after achieving a normal overjet.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the nasolabial angle.</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Measurement of the mean change in nasolabial angle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Molar anchorage loss</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Measurement of the mean change in the antero-posterior position of the first molar crown</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction from treatment with either the labial or lingual biocreative therapy</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Detected by using a questionnaire filled by the patients at the end of the retraction period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the transverse dimension of the upper arch.</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Detected through measurement of the mean change of the inter-canine and inter-molar width from the baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vertical movement of the crown of the six maxillary anterior teeth</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Detected by measurement of the mean change in the vertical linear distance from the incisal edge/cusp tip of every tooth to the palatal plane</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>point A to Nasion perp plane</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Measurement of the mean change in the position of point A from the Nasion perpendicular plane</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time duration required to complete the retraction phase.</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Recorded in months and days, from the start till the end of retraction period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in inter-labial gap</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Measurement of the mean change in inter-labial gap</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>upper lip position</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Change in the position of the upper lip in the antero-posterior dimension</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lower lip position</measure>
    <time_frame>Expected average of 10 months</time_frame>
    <description>Change in the position of the lower lip in the antero-posterior dimension</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Malocclusion, Angle Class II, Division 1</condition>
  <arm_group>
    <arm_group_label>Labial biocreative therapy group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Upper six anterior teeth will be bonded (0.018-inch slot brackets), leveled and aligned until reaching 0.017*0.025 stainless steel archwire.&#xD;
Right and left bracket head mini-screw (1.6*8 mm) will be inserted under local anaesthetic into the inter-radicular space between upper second premolar and first molar at the level of mucogingival junction. Crimpable hooks (10 mm) will be crimped onto the archwire between the upper lateral incisor and canine. 200 grams retraction force will be applied using NiTi coil springs from the hooks to the minscrew on both sides. Overlay reverse curve 0.016*0.022 NiTi will be inserted posteriorly into the mini-screw and ligated anteriorly to the archwire in the midline.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lingual biocreative therapy group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>En masse retraction of the six anterior teeth was accomplished using a lingual retractor bonded on to the lingual surface of the 6 anterior teeth, C-palatal plate fixed near the median palatal suture with 3 micro-screws, and Nickel Titanium (Ni-Ti) closing coil springs to apply a force of 200 g per side (total 400 g) directly from the C-plate to the lingual retractor.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biocreative therapy</intervention_name>
    <arm_group_label>Labial biocreative therapy group</arm_group_label>
    <arm_group_label>Lingual biocreative therapy group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Full permanent dentition (excluding third molars)&#xD;
&#xD;
          -  Angle class II malocclusion with increased overjet. Treatment plan includes extraction&#xD;
             of the upper first premolars and retraction of the maxillary anterior teeth with&#xD;
             maximum anchorage.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Systemic diseases (examples include bleeding disorders, bisphosphonate therapy,&#xD;
             chemotherapy, and radiotherapy) or craniofacial anomaly.&#xD;
&#xD;
               -  Previous orthodontic treatment.&#xD;
&#xD;
               -  Obvious periodontal disease and signs of bone loss.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mais M Sadek, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate lecturerof Orthodontics, Ain Shams University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Noha E Sabet, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Professor and Head of Orthodontic Department, Ain Shams University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Islam T Hassan, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Professor of Orthodontics, Ain Shams University</affiliation>
  </overall_official>
  <reference>
    <citation>Upadhyay M, Yadav S, Nagaraj K, Patil S. Treatment effects of mini-implants for en-masse retraction of anterior teeth in bialveolar dental protrusion patients: a randomized controlled trial. Am J Orthod Dentofacial Orthop. 2008 Jul;134(1):18-29.e1. doi: 10.1016/j.ajodo.2007.03.025.</citation>
    <PMID>18617099</PMID>
  </reference>
  <reference>
    <citation>Chung KR, Cho JH, Kim SH, Kook YA, Cozzani M. Unusual extraction treatment in Class II division 1 using C-orthodontic mini-implants. Angle Orthod. 2007 Jan;77(1):155-66. doi: 10.2319/020106-35R.1.</citation>
    <PMID>17029536</PMID>
  </reference>
  <reference>
    <citation>Chung KR, Kim SH, Kook YA, Son JH. Anterior torque control using partial-osseointegrated mini-implants: biocreative therapy type I technique. World J Orthod. 2008 Summer;9(2):95-104.</citation>
    <PMID>18575303</PMID>
  </reference>
  <reference>
    <citation>Chung KR, Kim SH, Kook YA, Choo H. Anterior torque control using partial-osseointegrated mini-implants: biocreative therapy type II technique. World J Orthod. 2008 Summer;9(2):105-13.</citation>
    <PMID>18575304</PMID>
  </reference>
  <reference>
    <citation>Su J, Liu J, Zhang D, Luo G, Chen L, Yu X, Lin Z, Zhang J. [Finite-element investigation on center of resistance of maxillary anterior teeth]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2014 Oct;31(5):994-1000. Chinese.</citation>
    <PMID>25764710</PMID>
  </reference>
  <reference>
    <citation>Miyawaki S, Yasuhara M, Koh Y. Discomfort caused by bonded lingual orthodontic appliances in adult patients as examined by retrospective questionnaire. Am J Orthod Dentofacial Orthop. 1999 Jan;115(1):83-8. doi: 10.1016/s0889-5406(99)70320-3.</citation>
    <PMID>9878962</PMID>
  </reference>
  <reference>
    <citation>Hong RK, Heo JM, Ha YK. Lever-arm and mini-implant system for anterior torque control during retraction in lingual orthodontic treatment. Angle Orthod. 2005 Jan;75(1):129-41. doi: 10.1043/0003-3219(2005)0752.0.CO;2.</citation>
    <PMID>15747828</PMID>
  </reference>
  <reference>
    <citation>Park YC, Choi YJ, Choi NC, Lee JS. Esthetic segmental retraction of maxillary anterior teeth with a palatal appliance and orthodontic mini-implants. Am J Orthod Dentofacial Orthop. 2007 Apr;131(4):537-44. doi: 10.1016/j.ajodo.2005.05.051.</citation>
    <PMID>17418722</PMID>
  </reference>
  <reference>
    <citation>Kim JS, Kim SH, Kook YA, Chung KR, Nelson G. Analysis of lingual en masse retraction combining a C-lingual retractor and a palatal plate. Angle Orthod. 2011 Jul;81(4):662-9. doi: 10.2319/100110-574.1. Epub 2011 Mar 14.</citation>
    <PMID>21406002</PMID>
  </reference>
  <reference>
    <citation>Kim SH, Hwang YS, Ferreira A, Chung KR. Analysis of temporary skeletal anchorage devices used for en-masse retraction: a preliminary study. Am J Orthod Dentofacial Orthop. 2009 Aug;136(2):268-76. doi: 10.1016/j.ajodo.2007.08.023.</citation>
    <PMID>19651358</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>January 15, 2019</last_update_submitted>
  <last_update_submitted_qc>January 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ain Shams University</investigator_affiliation>
    <investigator_full_name>Mais Medhat Sadek</investigator_full_name>
    <investigator_title>Assistant lecturer, Department of Orthodontics, Faculty of Dentistry</investigator_title>
  </responsible_party>
  <keyword>en masse retraction</keyword>
  <keyword>biocreative therapy</keyword>
  <keyword>class II</keyword>
  <keyword>skeletal anchorage</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malocclusion</mesh_term>
    <mesh_term>Malocclusion, Angle Class II</mesh_term>
    <mesh_term>Overbite</mesh_term>
  </condition_browse>
  <!-- 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/NCT03239275
org study id: ORD14-1D
nct id: NCT03239275
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to compare the effectiveness and efficiency of labial versus
      lingual biocreative therapy in achieving en masse retraction of the maxillary anterior teeth
      in subjects with class II malocclusion requiring upper first premolar extraction.
1. Background:

           Maximum anchorage is commonly required in patients with severe protrusion. Conventional
           retraction by sliding mechanics in extraction cases have been associated with variable
           degrees of anchorage loss. Use of miniscrew for reinforcement of orthodontic anchorage
           has become increasingly popular in recent years. Miniscrews are convenient, save time,
           and do not require patient cooperation. However, sliding mechanics with direct anchorage
           from mini-screw can have several biomechanical drawbacks. The force used during
           retraction is not reciprocal, posteriorly it is negated by the miniscrew, not by teeth.
           As a result, either the entire arch or the anterior segment rotates around the center of
           resistance. These mechanics produce posterior open bite and anterior deep overbite. To
           avoid this problem, Chung et al, introduced the technique that minimizes side effects by
           replacing the posterior appliance segments with the partially osteointegrated C-implant.
           This system was called "biocreative therapy".

           With the bio-creative approach, true intrusion vectors on the anterior teeth can be
           applied without unwanted reactive forces affecting the posterior teeth, the posterior
           teeth are left intact.

           In Labial biocreative therapy type I, a 0.016 × 0.022-in stainless steel utility
           archwire is placed from the anterior segment into the implant tube, and gable bends are
           used to generate an anterior torque moment on the anterior segment of the teeth to
           provide bodily movement during en-masse retraction. On the other hand, in biocreative
           therapy type II, en masse anterior retraction is accomplished by applying retraction
           force via NiTi coil springs between an anterior retraction hook placed between the
           lateral incisor and the canine and the skeletal anchorage. An overlay intrusion arch
           wire is used to generate torque on the anterior segment of teeth; thereby various
           patterns of tooth movement can be obtained through the combination of intrusion force,
           retraction force, and length of the retraction hook. Location and management of the
           center of resistance (Cres) with respect to retraction force vectors is critical. The
           clinician should select the length of a power arm according to the desired type of tooth
           movement; controlled lingual crown tipping, root tipping, or bodily movement.

           Adult orthodontics is an increasing part of the orthodontic practice. However, adult
           patients are often annoyed by the appearance of labial brackets and tend to delay or
           avoid starting orthodontic treatment. Lingual orthodontics is a viable option for these
           patients as being "invisible orthodontic treatment". The disadvantages of lingual
           orthodontics include the excessive chair time, complicated bio-mechanics, patient
           discomfort, expensive lab procedures, and high material prices. However, several
           innovations have improved the use of lingual orthodontics, such as customized lingual
           brackets and two-dimensional lingual brackets that can be bonded directly. Nonetheless,
           the efficient control of anterior torque and intrusion during retraction continues to be
           a limiting challenge.

           Mini-implants placed on each side of the palate have been used in conjunction with
           lingual orthodontics to avoid uncontrolled tipping and the deepening of the anterior
           bite during en masse retraction. A lever arm is soldered to the main lingual arch wire.
           This moves the force vector apically and closer to the center of resistance, thereby
           allowing better control of torque during retraction. However, play within the slot
           allows some of the torque to be lost during retraction. In addition, unwanted canting of
           the occlusal plane may occur if bilateral mini-implants are not in the same horizontal
           plane, due to different force vectors generated during retraction. Moreover, the sliding
           mechanics may be adversely affected by friction within bracket slots and tubes, causing
           unwanted distalization of posterior teeth.

           Lingual Biocreative therapy for anterior retraction offers several advantages. En masse
           retraction of the maxillary anterior dentition is achieved using C-lingual retractor and
           C-palatal plate. The C-lingual retractor is bonded to the lingual surfaces of the upper
           six anteriors, providing excellent esthetics. The C-palatal plate is fixed near the
           median palatal suture with mini-implants. The upper posterior orthodontic appliances are
           not needed as anchorage for 3-dimensional retraction of the upper anteriors.

           Lingual biocreative therapy technique can be used to provide patients with esthetic
           treatment, excellent anchorage control offered by skeletal anchorage, rapid and
           controlled retraction, simplified orthodontic bio-mechanics, and avoiding unnecessary
           use of complex orthodontic devices. Posterior teeth are not disturbed by friction in the
           appliance.

           As the majority of research work related to biocreative therapy technique was mainly
           case reports, three-dimensional finite element analyses, and three retrospective studies
           using two-dimensional cephalometric data, and the fact that no studies; up to the time
           of this writing; compared the labial and lingual biocreative techniques, the idea of
           this study has aroused as to use the advanced technology of three-dimensional imaging to
           clinically evaluate and compare the effects of labial and lingual biocreative therapy
           for en masse retraction of the maxillary anterior teeth.

        2. Research Hypothesis:

           The null hypothesis (H0) of this research is that there will be no statistically
           significant differences between labial and lingual biocreative therapy in the mean
           change in the upper incisor inclination after en masse retraction of the anterior teeth
           in subjects with class II malocclusion requiring upper first premolar extraction.

        3. Objectives:

           The primary objective of this study is to determine if there will be statistically
           significant differences between labial and lingual biocreative therapy in the mean
           change in the upper incisor inclination after en masse retraction of the anterior teeth.

           Secondary objectives include:

           To compare between labial and lingual biocreative therapy regarding:

             -  Changes in the soft tissue parameters including the nasolabial angle, inter-labial
                gap, and position of the upper and lower lips in the antero-posterior dimension;
                that would contribute to soft tissue profile correction.

             -  Molar anchorage loss.

             -  Patient satisfaction from treatment with either the labial or lingual biocreative
                therapy.

             -  Vertical movement of the crown of the six maxillary anterior teeth.

             -  Changes in the transverse dimension of the upper arch.

             -  Skeletal measurements including the mean change in the position of point A from the
                Nasion perpendicular plane and change in the SNA angle.

             -  Time duration required to complete the retraction phase.

        4. Study design According to the norms of the CONSORT STATEMENT, this study will be
           clinical with intervention, in which the allocation of the subjects will be randomized
           (block randomization). This study will be parallel with blinding for the outcome
           assessors. The primary purpose of this study will be treatment.

        5. Participants - Settings and locations where the data are collected The treatment will be
           performed in the outpatient clinics of Department of Orthodontics of Ain Shams
           University. This public university predominantly serves low-income population living in
           Cairo, Egypt. Data will be collected from January 2016 through November 2017.

        6. Interventions Two groups will receive treatment. Group 1 will be treated with the labial
           biocreative therapy group until the achievement of normal overjet (1 to 3 mm).

      Group 2 will be treated with lingual biocreative therapy group until the achievement of
      normal overjet (1 to 3 mm).

      7a. Sample size Sample size calculation was based on the studies by Kim et al and Kim et al.
      For the labial group, a mean change in the upper incisor inclination to SN plane of 15.33
      degrees, with a standard deviation of 6.85 was reported by Kim et al who compared
      pre-treatment cephalometric radiographs with those taken after en-masse retraction of the 6
      anterior teeth using temporary skeletal anchorage devices as the exclusive source of
      anchorage. No brackets or bands were placed on the posterior dentition during retraction.
      Regarding the lingual group, the mean change in the upper incisor inclination to SN plane of
      7.8 degrees, with a standard deviation of 5.5 was reported by Kim et al who compared
      pre-treatment cephalometric radiographs with those taken after en-masse retraction of the 6
      anterior teeth using the lingual biocreative therapy technique.

      The effect size ratio was calculated to be 1.212 using G*power software (Universität
      Düsseldorf, Germany). A t-test assuming equal variance for two independent groups was used
      and the power was set as 0.8, allocation ratio of 1:1 and the Type I error probability
      (alpha) associated with this test was set as 0.05. Results of the test showed that "the group
      sample sizes of 12 each would achieve 80.09% power to reject the null hypothesis of equal
      means with a significance level (alpha) of 0.05 using a two-sided two-sample equal variance
      t-test".

      Therefore, 24 subjects will be needed, with 12 subjects in each group. To account for patient
      loss to follow up (attrition), a sample size of 30 patients will be selected and divided into
      two groups, fifteen each.

      7b. Interim analysis and stopping guidelines In both groups, in case of mobility in the
      skeletal anchorage device used in any subject, the load will be removed for about two weeks
      and oral hygiene instructions will be reinforced. After that, the load will be restored. If
      the mobility persists, surgical exposure of the skeletal anchorage device will be done and
      either insertion of longer mini screws or a change in the position of the skeletal anchorage
      device will be done.

      Any harms, adverse effects or unintended effects of the study intervention will be documented
      and reported. Post-surgical swelling and pain are anticipated and will be addressed by
      antibiotics and pain killers. Other unanticipated surgical harms have to be immediately
      managed and will be reported. Harms related to the orthodontic appliances will be managed by
      the principal investigator.

      8. Randomization 8a. Sequence generation The randomization of the recruited subjects will be
      done with a randomized list, using random.org website. This list is made by an individual not
      involved in the clinical trial (A.Z.) 8b. Type The type of randomization will be block
      randomization. The number of blocks and block size will be blinded to the investigators.

      9. Allocation and concealment mechanism

        -  Each patient will be allocated a number from sequentially numbered opaque sealed
           envelopes after fulfilment of the inclusion criteria and signing the informed consent to
           be enrolled in the study.

        -  According to the number, the patients will be then allocated into one of the groups
           using a randomization table.

           10. Implementation Before the beginning of the research, the allocation sequence will be
           generated by a person not involved in the study (Dr A.Z.). The random list will be
           sealed from the principal investigator who will enrol participants. After the
           participant takes a sealed number, A.Z. will be contacted to implement the allocation.
           All the study contributors will have no access to the random list. The envelopes will be
           closed with the type of treatment selected for storage of the information.

           11. Blinding Blinding will be carried out only for the data assessment because the
           researchers, participants and subjects can not be blinded. Therefore, a person who does
           not know the nature of the trial will analyze the data.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Type of anterior tooth movement.
time frame: Expected average of 10 months
description: This would be detected by measurement of the mean change in bucco-lingual inclination of every anterior tooth from the baseline. This outcome will be measured after achieving a normal overjet.
measure: Change in the nasolabial angle.
time frame: Expected average of 10 months
description: Measurement of the mean change in nasolabial angle
measure: Molar anchorage loss
time frame: Expected average of 10 months
description: Measurement of the mean change in the antero-posterior position of the first molar crown
measure: Patient satisfaction from treatment with either the labial or lingual biocreative therapy
time frame: Expected average of 10 months
description: Detected by using a questionnaire filled by the patients at the end of the retraction period
measure: Changes in the transverse dimension of the upper arch.
time frame: Expected average of 10 months
description: Detected through measurement of the mean change of the inter-canine and inter-molar width from the baseline
measure: Vertical movement of the crown of the six maxillary anterior teeth
time frame: Expected average of 10 months
description: Detected by measurement of the mean change in the vertical linear distance from the incisal edge/cusp tip of every tooth to the palatal plane
measure: point A to Nasion perp plane
time frame: Expected average of 10 months
description: Measurement of the mean change in the position of point A from the Nasion perpendicular plane
measure: Time duration required to complete the retraction phase.
time frame: Expected average of 10 months
description: Recorded in months and days, from the start till the end of retraction period
measure: change in inter-labial gap
time frame: Expected average of 10 months
description: Measurement of the mean change in inter-labial gap
measure: upper lip position
time frame: Expected average of 10 months
description: Change in the position of the upper lip in the antero-posterior dimension
measure: Lower lip position
time frame: Expected average of 10 months
description: Change in the position of the lower lip in the antero-posterior dimension
arm group label: Labial biocreative therapy group
arm group type: Experimental
description: Upper six anterior teeth will be bonded (0.018-inch slot brackets), leveled and aligned until reaching 0.017*0.025 stainless steel archwire.
Right and left bracket head mini-screw (1.6*8 mm) will be inserted under local anaesthetic into the inter-radicular space between upper second premolar and first molar at the level of mucogingival junction. Crimpable hooks (10 mm) will be crimped onto the archwire between the upper lateral incisor and canine. 200 grams retraction force will be applied using NiTi coil springs from the hooks to the minscrew on both sides. Overlay reverse curve 0.016*0.022 NiTi will be inserted posteriorly into the mini-screw and ligated anteriorly to the archwire in the midline.
arm group label: Lingual biocreative therapy group
arm group type: Active Comparator
description: En masse retraction of the six anterior teeth was accomplished using a lingual retractor bonded on to the lingual surface of the 6 anterior teeth, C-palatal plate fixed near the median palatal suture with 3 micro-screws, and Nickel Titanium (Ni-Ti) closing coil springs to apply a force of 200 g per side (total 400 g) directly from the C-plate to the lingual retractor.
intervention type: Procedure
intervention name: Biocreative therapy
arm group label: Labial biocreative therapy group
arm group label: Lingual biocreative therapy group
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 25 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mais M Sadek, MSc
role: Principal Investigator
affiliation: Associate lecturerof Orthodontics, Ain Shams University
last name: Noha E Sabet, PhD
role: Study Chair
affiliation: Professor and Head of Orthodontic Department, Ain Shams University
last name: Islam T Hassan, PhD
role: Study Director
affiliation: Professor of Orthodontics, Ain Shams University
citation: Upadhyay M, Yadav S, Nagaraj K, Patil S. Treatment effects of mini-implants for en-masse retraction of anterior teeth in bialveolar dental protrusion patients: a randomized controlled trial. Am J Orthod Dentofacial Orthop. 2008 Jul;134(1):18-29.e1. doi: 10.1016/j.ajodo.2007.03.025.
PMID: 18617099
citation: Chung KR, Cho JH, Kim SH, Kook YA, Cozzani M. Unusual extraction treatment in Class II division 1 using C-orthodontic mini-implants. Angle Orthod. 2007 Jan;77(1):155-66. doi: 10.2319/020106-35R.1.
PMID: 17029536
citation: Chung KR, Kim SH, Kook YA, Son JH. Anterior torque control using partial-osseointegrated mini-implants: biocreative therapy type I technique. World J Orthod. 2008 Summer;9(2):95-104.
PMID: 18575303
citation: Chung KR, Kim SH, Kook YA, Choo H. Anterior torque control using partial-osseointegrated mini-implants: biocreative therapy type II technique. World J Orthod. 2008 Summer;9(2):105-13.
PMID: 18575304
citation: Su J, Liu J, Zhang D, Luo G, Chen L, Yu X, Lin Z, Zhang J. [Finite-element investigation on center of resistance of maxillary anterior teeth]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2014 Oct;31(5):994-1000. Chinese.
PMID: 25764710
citation: Miyawaki S, Yasuhara M, Koh Y. Discomfort caused by bonded lingual orthodontic appliances in adult patients as examined by retrospective questionnaire. Am J Orthod Dentofacial Orthop. 1999 Jan;115(1):83-8. doi: 10.1016/s0889-5406(99)70320-3.
PMID: 9878962
citation: Hong RK, Heo JM, Ha YK. Lever-arm and mini-implant system for anterior torque control during retraction in lingual orthodontic treatment. Angle Orthod. 2005 Jan;75(1):129-41. doi: 10.1043/0003-3219(2005)0752.0.CO;2.
PMID: 15747828
citation: Park YC, Choi YJ, Choi NC, Lee JS. Esthetic segmental retraction of maxillary anterior teeth with a palatal appliance and orthodontic mini-implants. Am J Orthod Dentofacial Orthop. 2007 Apr;131(4):537-44. doi: 10.1016/j.ajodo.2005.05.051.
PMID: 17418722
citation: Kim JS, Kim SH, Kook YA, Chung KR, Nelson G. Analysis of lingual en masse retraction combining a C-lingual retractor and a palatal plate. Angle Orthod. 2011 Jul;81(4):662-9. doi: 10.2319/100110-574.1. Epub 2011 Mar 14.
PMID: 21406002
citation: Kim SH, Hwang YS, Ferreira A, Chung KR. Analysis of temporary skeletal anchorage devices used for en-masse retraction: a preliminary study. Am J Orthod Dentofacial Orthop. 2009 Aug;136(2):268-76. doi: 10.1016/j.ajodo.2007.08.023.
PMID: 19651358
responsible party type: Principal Investigator
investigator affiliation: Ain Shams University
investigator full name: Mais Medhat Sadek
investigator title: Assistant lecturer, Department of Orthodontics, Faculty of Dentistry
mesh term: Malocclusion
mesh term: Malocclusion, Angle Class II
mesh term: Overbite