<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/NCT03257228</url>
  </required_header>
  <id_info>
    <org_study_id>BM 1.62</org_study_id>
    <nct_id>NCT03257228</nct_id>
  </id_info>
  <brief_title>The Association Between Diabetes Mellitus, Oral Lichen Planus and Insulin-like Growth Factors 1 and 2 (IGF1 and IGF2)</brief_title>
  <official_title>The Association Between Diabetes Mellitus, Oral Lichen Planus and Insulin-like Growth Factors 1 and 2 (IGF1 and IGF2)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zagreb</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Zagreb</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Diabetes mellitus is among the most common chronic diseases, with significant and well&#xD;
      documented impact on oral cavity health. Among the most common diseases of the oral cavity&#xD;
      mucosa and complications in patients with impaired glucose metabolism and diabetes mellitus&#xD;
      is oral lichen ruber (OLR), which according to World Health Organisation (WHO) is considered&#xD;
      potentially malignant disorder. It was found that lichen ruber in diabetes mellitus has a&#xD;
      much more aggressive clinical course in the form of atrophic-erosive and ulcerative lesions&#xD;
      showing an increased tendency to malignant transformation. Although OLR etiology is unknown,&#xD;
      evidence suggests cell-mediated autoimmune pathogenesis. OLR epithelial cells show anomalies&#xD;
      in both enzymatic activity and carbohydrate metabolism, which may be related to hormones&#xD;
      regulating carbohydrate, insulin and insulin-like growth factors 1 and 2 (IGF-1 and IGF-2)&#xD;
      metabolism. The hypothesis of our research is that patients with diabetes mellitus and oral&#xD;
      lichen ruber lesions will have a disturbance of insulin-like growth factors 1 and 2 and hence&#xD;
      a greater risk of malignant transformation, compared to patients with oral lichen ruber&#xD;
      without diabetes and healthy patients without alterations in the oral mucosa.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Oral lichen ruber (OLR) in the diabetes mellitus patients has more aggressive clinical course&#xD;
      in the form of atrophic-erosive and ulcerative lesions showing an increased tendency to&#xD;
      malignant transformation. OLR epithelial cells show anomalies in both enzymatic activity and&#xD;
      carbohydrate metabolism, which may be related to hormones regulating carbohydrate, insulin&#xD;
      and insulin-like Growth Factors 1 and 2 (IGF-1 and IGF-2) metabolism. The role of&#xD;
      insulin-like growth factors (IGFs) is of great importance in normal growth and cell&#xD;
      development (cell proliferation, differentiation and apoptosis), and is involved in different&#xD;
      aspects of cell transformation in malignant phenotype. A change in the expression of IGF1,&#xD;
      IGF2 and IGF2R proteins is described in several types of malignant tumors including oral&#xD;
      cancer. However, data on their role in the development of malignant lesions of the oral&#xD;
      cavity are scarce, and the results are inconsistent. Our hypothesis is that patients with&#xD;
      diabetes mellitus and oral lichen ruber lesions will have a disturbance of insulin-like&#xD;
      growth factors 1 and 2 and hence a greater risk of malignant transformation, compared to&#xD;
      patients with oral lichen ruber without diabetes and healthy patients without alterations in&#xD;
      the oral mucosa.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2014</start_date>
  <completion_date type="Actual">November 1, 2015</completion_date>
  <primary_completion_date type="Actual">November 1, 2015</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>Insulin like growth factors in patients with OLP and diabetes mellitus</measure>
    <time_frame>2014-2015</time_frame>
    <description>Evaluation of the Insulin-like growth factor 1 and 2 (IGF1 and IGF 2) in patients with oral lichen planus and diabetes mellitus</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">24</enrollment>
  <condition>Oral Lichen Planus</condition>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>oral lichen planus and diabetes mellitus</arm_group_label>
    <description>Histopathologically confirmed samples of oral lichen planus underwent immunohistochemical analysis of IGF1 and IGF2 expression. Blood glucose level was determined one day before taking biopsy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>oral lichen planus</arm_group_label>
    <description>Histopathologically confirmed samples of oral lichen planus underwent immunohistochemical analysis of IGF1 and IGF2 expression. Blood glucose level was determined one day before taking biopsy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy mucosa</arm_group_label>
    <description>Samples of healthy mucosa underwent immunohistochemical analysis of IGF1 and IGF2 expression. Blood glucose level was determined one day before taking mucosa samples.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>comparative semiquantitative immunohistochemistry</intervention_name>
    <arm_group_label>healthy mucosa</arm_group_label>
    <arm_group_label>oral lichen planus</arm_group_label>
    <arm_group_label>oral lichen planus and diabetes mellitus</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Biopsy samples of oral mucosa&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The patients included in the study are patients with oral lichen ruber referred to the&#xD;
        Department of Oral Medicine, University of Zagreb. Healthy mucosa samples were taken from&#xD;
        healthy volunteers referred for alveotomy of wisdom tooth to the Department of Oral&#xD;
        Surgery, School of Dental Medicine, University of Zagreb.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histopathologically confirmed oral lichen ruber patients, with and without diabetes&#xD;
             mellitus&#xD;
&#xD;
          -  healthy volunteers referred for alveolotomy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  non-consent patients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
  </eligibility>
  <reference>
    <citation>Djiogue S, Nwabo Kamdje AH, Vecchio L, Kipanyula MJ, Farahna M, Aldebasi Y, Seke Etet PF. Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer. 2013 Jan 7;20(1):R1-R17. doi: 10.1530/ERC-12-0324. Print 2013 Feb.</citation>
    <PMID>23207292</PMID>
  </reference>
  <reference>
    <citation>Cohen DH, LeRoith D. Obesity, type 2 diabetes, and cancer: the insulin and IGF connection. Endocr Relat Cancer. 2012 Sep 5;19(5):F27-45. doi: 10.1530/ERC-11-0374. Print 2012 Oct.</citation>
    <PMID>22593429</PMID>
  </reference>
  <reference>
    <citation>Sarfstein R, Friedman Y, Attias-Geva Z, Fishman A, Bruchim I, Werner H. Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners. PLoS One. 2013 Apr 19;8(4):e61537. doi: 10.1371/journal.pone.0061537. Print 2013.</citation>
    <PMID>23620761</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>August 29, 2017</last_update_submitted>
  <last_update_submitted_qc>August 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Zagreb</investigator_affiliation>
    <investigator_full_name>Božana Lončar Brzak</investigator_full_name>
    <investigator_title>Asisstant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lichen Planus, Oral</mesh_term>
    <mesh_term>Lichen Planus</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03257228
org study id: BM 1.62
nct id: NCT03257228
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Diabetes mellitus is among the most common chronic diseases, with significant and well
      documented impact on oral cavity health. Among the most common diseases of the oral cavity
      mucosa and complications in patients with impaired glucose metabolism and diabetes mellitus
      is oral lichen ruber (OLR), which according to World Health Organisation (WHO) is considered
      potentially malignant disorder. It was found that lichen ruber in diabetes mellitus has a
      much more aggressive clinical course in the form of atrophic-erosive and ulcerative lesions
      showing an increased tendency to malignant transformation. Although OLR etiology is unknown,
      evidence suggests cell-mediated autoimmune pathogenesis. OLR epithelial cells show anomalies
      in both enzymatic activity and carbohydrate metabolism, which may be related to hormones
      regulating carbohydrate, insulin and insulin-like growth factors 1 and 2 (IGF-1 and IGF-2)
      metabolism. The hypothesis of our research is that patients with diabetes mellitus and oral
      lichen ruber lesions will have a disturbance of insulin-like growth factors 1 and 2 and hence
      a greater risk of malignant transformation, compared to patients with oral lichen ruber
      without diabetes and healthy patients without alterations in the oral mucosa.
Oral lichen ruber (OLR) in the diabetes mellitus patients has more aggressive clinical course
      in the form of atrophic-erosive and ulcerative lesions showing an increased tendency to
      malignant transformation. OLR epithelial cells show anomalies in both enzymatic activity and
      carbohydrate metabolism, which may be related to hormones regulating carbohydrate, insulin
      and insulin-like Growth Factors 1 and 2 (IGF-1 and IGF-2) metabolism. The role of
      insulin-like growth factors (IGFs) is of great importance in normal growth and cell
      development (cell proliferation, differentiation and apoptosis), and is involved in different
      aspects of cell transformation in malignant phenotype. A change in the expression of IGF1,
      IGF2 and IGF2R proteins is described in several types of malignant tumors including oral
      cancer. However, data on their role in the development of malignant lesions of the oral
      cavity are scarce, and the results are inconsistent. Our hypothesis is that patients with
      diabetes mellitus and oral lichen ruber lesions will have a disturbance of insulin-like
      growth factors 1 and 2 and hence a greater risk of malignant transformation, compared to
      patients with oral lichen ruber without diabetes and healthy patients without alterations in
      the oral mucosa.
observational model: Cohort
time perspective: Prospective
measure: Insulin like growth factors in patients with OLP and diabetes mellitus
time frame: 2014-2015
description: Evaluation of the Insulin-like growth factor 1 and 2 (IGF1 and IGF 2) in patients with oral lichen planus and diabetes mellitus
arm group label: oral lichen planus and diabetes mellitus
description: Histopathologically confirmed samples of oral lichen planus underwent immunohistochemical analysis of IGF1 and IGF2 expression. Blood glucose level was determined one day before taking biopsy.
arm group label: oral lichen planus
description: Histopathologically confirmed samples of oral lichen planus underwent immunohistochemical analysis of IGF1 and IGF2 expression. Blood glucose level was determined one day before taking biopsy.
arm group label: healthy mucosa
description: Samples of healthy mucosa underwent immunohistochemical analysis of IGF1 and IGF2 expression. Blood glucose level was determined one day before taking mucosa samples.
intervention type: Genetic
intervention name: comparative semiquantitative immunohistochemistry
arm group label: healthy mucosa
arm group label: oral lichen planus
arm group label: oral lichen planus and diabetes mellitus
Biopsy samples of oral mucosa
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
citation: Djiogue S, Nwabo Kamdje AH, Vecchio L, Kipanyula MJ, Farahna M, Aldebasi Y, Seke Etet PF. Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer. 2013 Jan 7;20(1):R1-R17. doi: 10.1530/ERC-12-0324. Print 2013 Feb.
PMID: 23207292
citation: Cohen DH, LeRoith D. Obesity, type 2 diabetes, and cancer: the insulin and IGF connection. Endocr Relat Cancer. 2012 Sep 5;19(5):F27-45. doi: 10.1530/ERC-11-0374. Print 2012 Oct.
PMID: 22593429
citation: Sarfstein R, Friedman Y, Attias-Geva Z, Fishman A, Bruchim I, Werner H. Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners. PLoS One. 2013 Apr 19;8(4):e61537. doi: 10.1371/journal.pone.0061537. Print 2013.
PMID: 23620761
responsible party type: Principal Investigator
investigator affiliation: University of Zagreb
investigator full name: Božana Lončar Brzak
investigator title: Asisstant Professor
mesh term: Lichen Planus, Oral
mesh term: Lichen Planus
mesh term: Diabetes Mellitus
sharing ipd: No