<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/NCT01663298</url>
  </required_header>
  <id_info>
    <org_study_id>10-1184</org_study_id>
    <secondary_id>1R01DE021052-01</secondary_id>
    <secondary_id>1UL1RR025747</secondary_id>
    <secondary_id>AWU</secondary_id>
    <nct_id>NCT01663298</nct_id>
  </id_info>
  <brief_title>Gene Expression Variation and Implant Wound Healing Among Smokers and Diabetics</brief_title>
  <official_title>FGF2 Promoter Hypermethylation and Implant Wound Healing Among Smokers and Diabetics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Dental and Craniofacial Research (NIDCR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Research Resources (NCRR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Periodontal wound healing is a complex multifactorial process that involves interactions&#xD;
      among various cells, growth factors, hormones and extracellular matrices. Although still&#xD;
      poorly understood, these interactions trigger a series of events that lead to new tissue&#xD;
      formation. One growth factor that plays an important role in wound healing is fibroblast&#xD;
      growth factor 2 (FGF2). Many animal and human studies have shown this protein is effective in&#xD;
      periodontal regeneration. Recently, epigenetic modifications, such as DNA methylation, have&#xD;
      been associated with changes in patterns of gene expression. Preliminary data suggests that&#xD;
      FGF2 gene may be differentially methylated in periodontal tissues. Aberrant gene promoter&#xD;
      methylation in smokers and diabetics has also been reported in many studies. However, the&#xD;
      role of DNA methylation in wound healing has not yet been investigated.&#xD;
&#xD;
      The investigators hypothesize that the methylation status of FGF2 gene can affect the levels&#xD;
      of FGF2 secreted during wound healing phase after dental implant surgery. The investigators&#xD;
      also hypothesize there exists a difference in methylation levels of FGF2 gene in healthy,&#xD;
      smoking and diabetic patients that can interfere with wound healing. The investigators seek&#xD;
      to determine whether DNA methylation plays a role in wound healing and whether the&#xD;
      methylation level of FGF2 gene varies among healthy, smoking and diabetic patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Periodontal wound healing is a complex multifactorial process that involves interactions&#xD;
      among various cells, growth factors, hormones and extracellular matrices. Although still&#xD;
      poorly understood, these interactions trigger a series of events that lead to new tissue&#xD;
      formation. One growth factor that plays an important role in wound healing is fibroblast&#xD;
      growth factor 2 (FGF2). FGF2 is a member of the heparin-binding growth factor family,&#xD;
      secreted by macrophages and endothelial cells. During the proliferative healing phase, it&#xD;
      stimulates fibroblast proliferation &amp; ECM synthesis, and increases chemotaxis, proliferation&#xD;
      and differentiation of endothelial cells. During the bone remodeling phase, FGF2 also&#xD;
      stimulates mesenchymal progenitor cell migration. Many animal and human studies have shown&#xD;
      FGF2 are effective in periodontal regeneration. In 1999, Murakami showed surgically treated&#xD;
      3-wall intrabony defect in dogs grafted with FGF2 was able to demonstrate significantly&#xD;
      greater cementum and bone formation. Four years later, his group again found that topical&#xD;
      application of rhbFGF in surgically treated class 2 furcation defects in dogs also showed&#xD;
      increase in formation of PDL, cementum and bone. In 2008, Kitamura performed a randomized&#xD;
      controlled study in humans with 2- or 3-wall intrabony periodontal defects and found that&#xD;
      rhbFGF was able to stimulate alveolar bone growth and PDL regeneration.&#xD;
&#xD;
      Recently, epigenetic modifications, such as DNA methylation, have been associated with&#xD;
      changes in patterns of gene expression that do not involve changes in DNA sequence. DNA&#xD;
      methylation is characterized by the addition of the methyl group onto cytokines within CpG&#xD;
      regions. Methylated CpG regions interfere with the access of transcription factors to the&#xD;
      promoter region, thereby silencing the gene. This DNA methylation phenomenon has important&#xD;
      regulatory functions in normal and pathological cellular processes. It was recognized that&#xD;
      alteration in the methylation states at the promoter regions of tumor suppressor genes are&#xD;
      implicated with cancer. A persistent inflammation was also observed to cause DNA methylation,&#xD;
      which inactivates suppressors of cytokine signaling and results in exaggerated cytokine&#xD;
      production. This makes an individual susceptible to periodontal disease. In our laboratory,&#xD;
      the investigators have discovered that periodontal disease is associated with increased DNA&#xD;
      methylation of the COX-2 promotor, especially the locus immediately adjacent to the NF-kB in&#xD;
      the promoter region. Preliminary data (not shown) suggests that FGF2 may be differentially&#xD;
      methylated in periodontal tissues. Aberrant gene promoter methylation in smokers and&#xD;
      diabetics has also been reported in many studies. However, the role of DNA methylation in&#xD;
      wound healing has not yet been investigated.&#xD;
&#xD;
      We hypothesize that the methylation status of FGF2 can affect the levels of FGF2 secreted&#xD;
      during wound healing phase after dental implant surgery. We also hypothesize there exists a&#xD;
      difference in methylation levels of FGF2 in healthy, smoking and diabetic patients that can&#xD;
      interfere with wound healing. We seek to determine whether DNA methylation plays a role in&#xD;
      wound healing and whether the methylation level of FGF2 varies among healthy, smoking and&#xD;
      diabetic patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2010</start_date>
  <completion_date type="Actual">February 23, 2016</completion_date>
  <primary_completion_date type="Actual">January 12, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>FGF2 methylation level</measure>
    <time_frame>On the day of implant surgery</time_frame>
    <description>Genomic DNA is isolated from the collected gingival tissue samples. Methylation alterations in FGF2 are detected through differential methylation hybridization using the EpiTect® Methyl qPCR single assay.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>FGF2 mRNA expression level</measure>
    <time_frame>On the day of implant surgery (DAY 0)</time_frame>
    <description>RNA is isolated from the collected gingival tissue samples and is then processed for gene expression analysis by quantitative real-time PCR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FGF2 protein level</measure>
    <time_frame>On the day of implant surgery (DAY 0) and 2, 4 and 6 weeks following implant surgery</time_frame>
    <description>Gingival crevicular fluid, obtained from the two adjacent sites closest to the implant location, is used to quantify specific FGF2 protein levels by ELISA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implant stability quotient (ISQ)</measure>
    <time_frame>4 and 6 weeks following implant surgery</time_frame>
    <description>The degree of implant stability at various time points following the surgery is measured using an Osstell ISQ instrument. An ISQ value, ranged between 1 and 100, is generated for each sample at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wound healing indices (WHI)</measure>
    <time_frame>2, 4 and 6 weeks following implant surgery</time_frame>
    <description>The degree of soft tissue healing at various time points following surgery is monitored by WHI.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Smoking</condition>
  <condition>Diabetes</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>Subjects must have never smoked and must be non-diabetic.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Smoking group</arm_group_label>
    <description>Subjects must have had at least 5 pack-years of self-reported smoking history, must be currently smoking and must be non-diabetic.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic group</arm_group_label>
    <description>Subjects must have type 2 diabetes. The condition must be diagnosed subjects must be treated by medications and/or insulin. A HbA1C test result either within past 3 months or performed in the first visit must be available. They must have never smoked.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Dental implant surgery</intervention_name>
    <description>Surgery involving placement of one dental implant, of either Astra Tech or Straumann system, is performed in all subjects within 2 weeks of screening examination. Implant placement is 1-stage, but can be either on edentulous ridges or in extraction sockets.This is not a randomized treatment arm/group design. The study is observational with regards to the analysis of tissue samples that are collected prior to the routine placement of implants. The implant choice is based upon patient needs and is not related to any outcome.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Diabetic group</arm_group_label>
    <arm_group_label>Smoking group</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Gingival tissues, gingival crevicular fluid, saliva&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients in the graduate periodontal clinic in the school of dentistry at the University of&#xD;
        North Carolina&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult males or females between the age of 18 and 70 years (inclusive)&#xD;
&#xD;
          -  Able and willing to follow study procedures and instructions&#xD;
&#xD;
          -  Have read, understood and signed an informed consent form&#xD;
&#xD;
          -  In good general health&#xD;
&#xD;
          -  Have one or more implant placements as their future treatment needs. The implant&#xD;
             placement can be either as one-stage or two-stage, and can be either in an edentulous&#xD;
             ridge or an extraction socket&#xD;
&#xD;
          -  Qualify for enrollment into one of the three study groups&#xD;
&#xD;
          -  Have probing depth ≤ 4 mm for all teeth at the same quadrant of implant placement.&#xD;
             Sites with probing depth 5 mm will also be included if bleeding on probing in these&#xD;
             sites are absent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have a chronic disease with oral manifestations&#xD;
&#xD;
          -  Exhibit gross oral pathology&#xD;
&#xD;
          -  Use of either antibiotics or NSAIDs within 1 month prior to screening examination&#xD;
&#xD;
          -  Chronic treatment (i.e. two weeks or more) with any medication known to affect&#xD;
             periodontal status (e.g. phenytoin, calcium, antagonists, cyclosporin, Coumadin)&#xD;
             within 1 month prior to screening examination&#xD;
&#xD;
          -  Systemic conditions, except smoking and diabetes, that are known to affect the&#xD;
             periodontal status&#xD;
&#xD;
          -  With active infectious diseases such as hepatitis, HIV or tuberculosis&#xD;
&#xD;
          -  Known to be pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Silvana Barros, DDS, PhD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>UNC Chapel Hill School of Dentistry</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Periodontology, UNC School of Dentistry</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Kaigler D, Cirelli JA, Giannobile WV. Growth factor delivery for oral and periodontal tissue engineering. Expert Opin Drug Deliv. 2006 Sep;3(5):647-62. doi: 10.1517/17425247.3.5.647.</citation>
    <PMID>16948560</PMID>
  </reference>
  <reference>
    <citation>Murakami S, Takayama S, Ikezawa K, Shimabukuro Y, Kitamura M, Nozaki T, Terashima A, Asano T, Okada H. Regeneration of periodontal tissues by basic fibroblast growth factor. J Periodontal Res. 1999 Oct;34(7):425-30. doi: 10.1111/j.1600-0765.1999.tb02277.x.</citation>
    <PMID>10685372</PMID>
  </reference>
  <reference>
    <citation>Murakami S, Takayama S, Kitamura M, Shimabukuro Y, Yanagi K, Ikezawa K, Saho T, Nozaki T, Okada H. Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs. J Periodontal Res. 2003 Feb;38(1):97-103. doi: 10.1034/j.1600-0765.2003.00640.x.</citation>
    <PMID>12558943</PMID>
  </reference>
  <reference>
    <citation>Kitamura M, Nakashima K, Kowashi Y, Fujii T, Shimauchi H, Sasano T, Furuuchi T, Fukuda M, Noguchi T, Shibutani T, Iwayama Y, Takashiba S, Kurihara H, Ninomiya M, Kido J, Nagata T, Hamachi T, Maeda K, Hara Y, Izumi Y, Hirofuji T, Imai E, Omae M, Watanuki M, Murakami S. Periodontal tissue regeneration using fibroblast growth factor-2: randomized controlled phase II clinical trial. PLoS One. 2008 Jul 2;3(7):e2611. doi: 10.1371/journal.pone.0002611.</citation>
    <PMID>18596969</PMID>
  </reference>
  <reference>
    <citation>Barros SP, Offenbacher S. Epigenetics: connecting environment and genotype to phenotype and disease. J Dent Res. 2009 May;88(5):400-8. doi: 10.1177/0022034509335868.</citation>
    <PMID>19493882</PMID>
  </reference>
  <reference>
    <citation>Gomez RS, Dutra WO, Moreira PR. Epigenetics and periodontal disease: future perspectives. Inflamm Res. 2009 Oct;58(10):625-9. doi: 10.1007/s00011-009-0041-7. Epub 2009 May 8.</citation>
    <PMID>19440658</PMID>
  </reference>
  <reference>
    <citation>Wilson AG. Epigenetic regulation of gene expression in the inflammatory response and relevance to common diseases. J Periodontol. 2008 Aug;79(8 Suppl):1514-9. doi: 10.1902/jop.2008.080172.</citation>
    <PMID>18673005</PMID>
  </reference>
  <reference>
    <citation>Ling C, Groop L. Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes. 2009 Dec;58(12):2718-25. doi: 10.2337/db09-1003. No abstract available.</citation>
    <PMID>19940235</PMID>
  </reference>
  <reference>
    <citation>Krupanidhi S, Sedimbi SK, Vaishnav G, Madhukar SS, Sanjeevi CB. Diabetes--role of epigenetics, genetics, and physiological factors. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009 Sep;34(9):837-45.</citation>
    <PMID>19779253</PMID>
  </reference>
  <reference>
    <citation>Simmons RA. Developmental origins of diabetes: the role of epigenetic mechanisms. Curr Opin Endocrinol Diabetes Obes. 2007 Feb;14(1):13-6. doi: 10.1097/MED.0b013e328013da5b.</citation>
    <PMID>17940413</PMID>
  </reference>
  <reference>
    <citation>Kuroda A, Rauch TA, Todorov I, Ku HT, Al-Abdullah IH, Kandeel F, Mullen Y, Pfeifer GP, Ferreri K. Insulin gene expression is regulated by DNA methylation. PLoS One. 2009 Sep 9;4(9):e6953. doi: 10.1371/journal.pone.0006953. Erratum In: PLoS One. 2009;4(10) 10.1371/annotation/947a8d4a-3585-4b23-ac84-b47a255a70d9.</citation>
    <PMID>19742322</PMID>
  </reference>
  <reference>
    <citation>Han W, Wang T, Reilly AA, Keller SM, Spivack SD. Gene promoter methylation assayed in exhaled breath, with differences in smokers and lung cancer patients. Respir Res. 2009 Sep 25;10(1):86. doi: 10.1186/1465-9921-10-86.</citation>
    <PMID>19781081</PMID>
  </reference>
  <reference>
    <citation>Belinsky SA, Palmisano WA, Gilliland FD, Crooks LA, Divine KK, Winters SA, Grimes MJ, Harms HJ, Tellez CS, Smith TM, Moots PP, Lechner JF, Stidley CA, Crowell RE. Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Res. 2002 Apr 15;62(8):2370-7.</citation>
    <PMID>11956099</PMID>
  </reference>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 1, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>February 11, 2020</last_update_submitted>
  <last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DNA methylation</keyword>
  <keyword>FGF2</keyword>
  <keyword>Wound healing</keyword>
  <keyword>Smoking</keyword>
  <keyword>Diabetes</keyword>
  <keyword>Implant</keyword>
  <!-- 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/NCT01663298
org study id: 10-1184
secondary id: 1R01DE021052-01
secondary id: 1UL1RR025747
secondary id: AWU
nct id: NCT01663298
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Periodontal wound healing is a complex multifactorial process that involves interactions
      among various cells, growth factors, hormones and extracellular matrices. Although still
      poorly understood, these interactions trigger a series of events that lead to new tissue
      formation. One growth factor that plays an important role in wound healing is fibroblast
      growth factor 2 (FGF2). Many animal and human studies have shown this protein is effective in
      periodontal regeneration. Recently, epigenetic modifications, such as DNA methylation, have
      been associated with changes in patterns of gene expression. Preliminary data suggests that
      FGF2 gene may be differentially methylated in periodontal tissues. Aberrant gene promoter
      methylation in smokers and diabetics has also been reported in many studies. However, the
      role of DNA methylation in wound healing has not yet been investigated.

      The investigators hypothesize that the methylation status of FGF2 gene can affect the levels
      of FGF2 secreted during wound healing phase after dental implant surgery. The investigators
      also hypothesize there exists a difference in methylation levels of FGF2 gene in healthy,
      smoking and diabetic patients that can interfere with wound healing. The investigators seek
      to determine whether DNA methylation plays a role in wound healing and whether the
      methylation level of FGF2 gene varies among healthy, smoking and diabetic patients.
Periodontal wound healing is a complex multifactorial process that involves interactions
      among various cells, growth factors, hormones and extracellular matrices. Although still
      poorly understood, these interactions trigger a series of events that lead to new tissue
      formation. One growth factor that plays an important role in wound healing is fibroblast
      growth factor 2 (FGF2). FGF2 is a member of the heparin-binding growth factor family,
      secreted by macrophages and endothelial cells. During the proliferative healing phase, it
      stimulates fibroblast proliferation & ECM synthesis, and increases chemotaxis, proliferation
      and differentiation of endothelial cells. During the bone remodeling phase, FGF2 also
      stimulates mesenchymal progenitor cell migration. Many animal and human studies have shown
      FGF2 are effective in periodontal regeneration. In 1999, Murakami showed surgically treated
      3-wall intrabony defect in dogs grafted with FGF2 was able to demonstrate significantly
      greater cementum and bone formation. Four years later, his group again found that topical
      application of rhbFGF in surgically treated class 2 furcation defects in dogs also showed
      increase in formation of PDL, cementum and bone. In 2008, Kitamura performed a randomized
      controlled study in humans with 2- or 3-wall intrabony periodontal defects and found that
      rhbFGF was able to stimulate alveolar bone growth and PDL regeneration.

      Recently, epigenetic modifications, such as DNA methylation, have been associated with
      changes in patterns of gene expression that do not involve changes in DNA sequence. DNA
      methylation is characterized by the addition of the methyl group onto cytokines within CpG
      regions. Methylated CpG regions interfere with the access of transcription factors to the
      promoter region, thereby silencing the gene. This DNA methylation phenomenon has important
      regulatory functions in normal and pathological cellular processes. It was recognized that
      alteration in the methylation states at the promoter regions of tumor suppressor genes are
      implicated with cancer. A persistent inflammation was also observed to cause DNA methylation,
      which inactivates suppressors of cytokine signaling and results in exaggerated cytokine
      production. This makes an individual susceptible to periodontal disease. In our laboratory,
      the investigators have discovered that periodontal disease is associated with increased DNA
      methylation of the COX-2 promotor, especially the locus immediately adjacent to the NF-kB in
      the promoter region. Preliminary data (not shown) suggests that FGF2 may be differentially
      methylated in periodontal tissues. Aberrant gene promoter methylation in smokers and
      diabetics has also been reported in many studies. However, the role of DNA methylation in
      wound healing has not yet been investigated.

      We hypothesize that the methylation status of FGF2 can affect the levels of FGF2 secreted
      during wound healing phase after dental implant surgery. We also hypothesize there exists a
      difference in methylation levels of FGF2 in healthy, smoking and diabetic patients that can
      interfere with wound healing. We seek to determine whether DNA methylation plays a role in
      wound healing and whether the methylation level of FGF2 varies among healthy, smoking and
      diabetic patients.
observational model: Cohort
time perspective: Prospective
measure: FGF2 methylation level
time frame: On the day of implant surgery
description: Genomic DNA is isolated from the collected gingival tissue samples. Methylation alterations in FGF2 are detected through differential methylation hybridization using the EpiTect® Methyl qPCR single assay.
measure: FGF2 mRNA expression level
time frame: On the day of implant surgery (DAY 0)
description: RNA is isolated from the collected gingival tissue samples and is then processed for gene expression analysis by quantitative real-time PCR.
measure: FGF2 protein level
time frame: On the day of implant surgery (DAY 0) and 2, 4 and 6 weeks following implant surgery
description: Gingival crevicular fluid, obtained from the two adjacent sites closest to the implant location, is used to quantify specific FGF2 protein levels by ELISA.
measure: Implant stability quotient (ISQ)
time frame: 4 and 6 weeks following implant surgery
description: The degree of implant stability at various time points following the surgery is measured using an Osstell ISQ instrument. An ISQ value, ranged between 1 and 100, is generated for each sample at each time point.
measure: Wound healing indices (WHI)
time frame: 2, 4 and 6 weeks following implant surgery
description: The degree of soft tissue healing at various time points following surgery is monitored by WHI.
arm group label: Control group
description: Subjects must have never smoked and must be non-diabetic.
arm group label: Smoking group
description: Subjects must have had at least 5 pack-years of self-reported smoking history, must be currently smoking and must be non-diabetic.
arm group label: Diabetic group
description: Subjects must have type 2 diabetes. The condition must be diagnosed subjects must be treated by medications and/or insulin. A HbA1C test result either within past 3 months or performed in the first visit must be available. They must have never smoked.
intervention type: Procedure
intervention name: Dental implant surgery
description: Surgery involving placement of one dental implant, of either Astra Tech or Straumann system, is performed in all subjects within 2 weeks of screening examination. Implant placement is 1-stage, but can be either on edentulous ridges or in extraction sockets.This is not a randomized treatment arm/group design. The study is observational with regards to the analysis of tissue samples that are collected prior to the routine placement of implants. The implant choice is based upon patient needs and is not related to any outcome.
arm group label: Control group
arm group label: Diabetic group
arm group label: Smoking group
Gingival tissues, gingival crevicular fluid, saliva
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Silvana Barros, DDS, PhD, MS
role: Principal Investigator
affiliation: UNC Chapel Hill School of Dentistry
facility: 
country: United States
citation: Kaigler D, Cirelli JA, Giannobile WV. Growth factor delivery for oral and periodontal tissue engineering. Expert Opin Drug Deliv. 2006 Sep;3(5):647-62. doi: 10.1517/17425247.3.5.647.
PMID: 16948560
citation: Murakami S, Takayama S, Ikezawa K, Shimabukuro Y, Kitamura M, Nozaki T, Terashima A, Asano T, Okada H. Regeneration of periodontal tissues by basic fibroblast growth factor. J Periodontal Res. 1999 Oct;34(7):425-30. doi: 10.1111/j.1600-0765.1999.tb02277.x.
PMID: 10685372
citation: Murakami S, Takayama S, Kitamura M, Shimabukuro Y, Yanagi K, Ikezawa K, Saho T, Nozaki T, Okada H. Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs. J Periodontal Res. 2003 Feb;38(1):97-103. doi: 10.1034/j.1600-0765.2003.00640.x.
PMID: 12558943
citation: Kitamura M, Nakashima K, Kowashi Y, Fujii T, Shimauchi H, Sasano T, Furuuchi T, Fukuda M, Noguchi T, Shibutani T, Iwayama Y, Takashiba S, Kurihara H, Ninomiya M, Kido J, Nagata T, Hamachi T, Maeda K, Hara Y, Izumi Y, Hirofuji T, Imai E, Omae M, Watanuki M, Murakami S. Periodontal tissue regeneration using fibroblast growth factor-2: randomized controlled phase II clinical trial. PLoS One. 2008 Jul 2;3(7):e2611. doi: 10.1371/journal.pone.0002611.
PMID: 18596969
citation: Barros SP, Offenbacher S. Epigenetics: connecting environment and genotype to phenotype and disease. J Dent Res. 2009 May;88(5):400-8. doi: 10.1177/0022034509335868.
PMID: 19493882
citation: Gomez RS, Dutra WO, Moreira PR. Epigenetics and periodontal disease: future perspectives. Inflamm Res. 2009 Oct;58(10):625-9. doi: 10.1007/s00011-009-0041-7. Epub 2009 May 8.
PMID: 19440658
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