<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/NCT03833310</url>
  </required_header>
  <id_info>
    <org_study_id>vosrd</org_study_id>
    <nct_id>NCT03833310</nct_id>
  </id_info>
  <brief_title>Novel Biomarkers in Inflammatory Bowel Disease</brief_title>
  <official_title>Novel Biomarkers in Diagnosis of Inflammatory Bowel Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The inflammatory bowel diseases represent a heterogeneous group of chronic , relapsing-&#xD;
      inflammatory disorders of the gastrointestinal tract. Crohn's disease and ulcerative colitis&#xD;
      are the two major clinical forms.The global incidence and prevalence of the inflammatory&#xD;
      bowel diseases has increased over the last 2-4 decades . Despite the great progress in&#xD;
      understanding the pathogenesis of these diseases, their etiology remains unclear .&#xD;
      Considerable effort has been devoted to the development of an accurate ,noninvasive&#xD;
      biomarkers that have increased diagnostic sensitivity and specificity .&#xD;
&#xD;
      Osteoprotegerin is a member of the Tumor Necrosis Factor Receptor superfamily of proteins.&#xD;
      Osteoprotegerin is of particular importance in bone metabolism, inflammation , tumorigenesis,&#xD;
      and other processes where cell differentiation, survival, and death are controlled.&#xD;
      Osteoprotegerin activates inflammation in the gut by stimulating immune cells, cytokines, and&#xD;
      the Necrosis factor-κappaB pathway .&#xD;
&#xD;
      Soluble Receptor activator of nuclear factor kappa-Β ligand is known as a type II membrane&#xD;
      protein and as a member of tumor necrosis factor superfamily . Soluble Receptor activator of&#xD;
      nuclear factor kappa-Β ligand has been identified to affect the immune system and a binding&#xD;
      partner of ( Osteoprotegerin ), and controls cell proliferation.The interactions between&#xD;
      Osteoprotegerin and Soluble Receptor activator of nuclear factor kappa-Β ligand, Soluble&#xD;
      Receptor activator of nuclear factor kappa-Β have relevance to inflammatory pathways. Soluble&#xD;
      Receptor activator of nuclear factor kappa-Β ligand- Soluble Receptor activator of nuclear&#xD;
      factor kappa-Β ligand binding activates pathways that contribute to the survival of&#xD;
      T-lymphocytes and dendritic cells .&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The inflammatory bowel diseases represent a heterogeneous group of chronic ,&#xD;
      relapsing-remitting inflammatory disorders of the gastrointestinal tract, and Crohn's disease&#xD;
      and ulcerative colitis are among the two major clinical forms The global incidence and&#xD;
      prevalence of The inflammatory bowel diseases has increased over the last 2-4 decades, likely&#xD;
      because of the adoption of a more &quot;western&quot; lifestyle as well as improved detection and&#xD;
      awareness . Despite the great progress in understanding the pathogenesis of these diseases,&#xD;
      their etiology remains unclear. Genetic, immune, and environmental factors are thought to&#xD;
      play a key role .&#xD;
&#xD;
      In the case of Crohn's disease , chronic inﬂammation can be localized in every&#xD;
      gastrointestinal tract segment and involves the full thickness of the intestinal wall. In&#xD;
      contrast ,in ulcerative colitis , mucosa and submucosa membranes of the large intestine are&#xD;
      usually involved The illness starts in the rectum and generally extends proximally through&#xD;
      the whole colon. . Both diseases differ in the localization and size of the segment involved.&#xD;
      There are also differences in clinical image, laboratory test results, and different&#xD;
      characteristics of complications. The course and grade of disease activity depend on many&#xD;
      factors, such as environmental influences , genetic features, changes in the intestinal&#xD;
      microbiota ecosystem, and immune factors .&#xD;
&#xD;
      The correct diagnosis of non-specific inflammatory bowel diseases as well as the&#xD;
      determination of disease activity, risk stratification , and prediction of response to&#xD;
      therapy still relies on a multidisciplinary approach based on clinical, laboratory,&#xD;
      endoscopic, and histologic examination . However, considerable effort has been devoted to the&#xD;
      development of an accurate panel of noninvasive bio markers that have increased diagnostic&#xD;
      sensitivity and specificity .&#xD;
&#xD;
      Osteoprotegerin , also known as is a member of the Tumor Necrosis Factor Receptor superfamily&#xD;
      of proteins. Osteoprotegerin is involved in many biological processes: its role is of&#xD;
      particular importance in bone metabolism, inflammation , tumorigenesis, and other processes&#xD;
      where cell differentiation, survival, and death are controlled. Osteoprotegerin was detected&#xD;
      in serum, mucosal biopsies, and in the stool .&#xD;
&#xD;
      The Osteoprotegerin gene is located on chromosome 8q23- 24.17. The mature OPG protein&#xD;
      contains 380 amino acids and consists of seven domains. The ﬁrst four domains (D1-D4) contain&#xD;
      cysteine-rich structures at the N terminus which are required for the inhibition of&#xD;
      osteoclast differentiation. The ﬁfth and the sixth domain (D5 and D6) are death-domains and&#xD;
      may be important in cytotoxic signals. The seventh domain, a C terminus heparin-binding site,&#xD;
      is involved in dimer osteoprotegerin formation .&#xD;
&#xD;
      Osteoprotegerin can be produced by a wide range of cell types, including osteoblasts, B&#xD;
      lymphocytes, dendritic cells, bone marrow stromal cells, epithelial cells, and&#xD;
      monocytes/macrophages. Osteoprotegerin activates and/or perpetuates inflammation in the gut&#xD;
      by stimulating immune cells, cytokines, and the Necrosis factor-kappa B pathway .&#xD;
&#xD;
      On the other hand, soluble Receptor activator of nuclear factor kappa-Β ligand , also known&#xD;
      as tumor necrosis factor ligand. soluble Receptor activator of nuclear factor kappa-Β ligand&#xD;
      is known as a type II membrane protein and as a member of tumor necrosis factor superfamily.&#xD;
&#xD;
      Soluble Receptor activator of nuclear factor kappa-Β ligand has been identified to affect the&#xD;
      immune system and control bone regeneration and remodeling, a binding partner of , and&#xD;
      controls cell proliferation. it is expressed in several tissues and organs including:&#xD;
      skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoblast, mammary&#xD;
      gland epithelial cells, prostate and pancreas. Variation in concentration levels of soluble&#xD;
      Receptor activator of nuclear factor kappa-Β ligand throughout several organs reconfirms the&#xD;
      importance of in tissue soluble Receptor activator of nuclear factor kappa-Β ligand growth&#xD;
      (particularly bone growth) and immune functions within the body .&#xD;
&#xD;
      The interactions between ,Osteoprotegerin,soluble Receptor activator of nuclear factor&#xD;
      kappa-Β ligand and soluble Receptor activator of nuclear factor kappa-Β also have relevance&#xD;
      to inflammatory pathways. - soluble binding Receptor activator of nuclear factor kappa-Β&#xD;
      binding activates several pathways that contribute to the survival of T-lymphocytes and&#xD;
      dendritic cells .&#xD;
&#xD;
      In addition, Osteoprotegerin is synthesized by dendritic and B-lymphocytes whereas soluble&#xD;
      Receptor activator of nuclear factor kappa-Β ligand is mainly produced by T-lymphocytes.&#xD;
      Moreover, soluble Receptor activator of nuclear factor kappa-Β ligand and various cytokines&#xD;
      e.g. Tumor Necrosis Factor α induce the synthesis of osteoprotegerin from immune cells. In&#xD;
      turn, the interruption of soluble Receptor activator of nuclear factor kappa-Β - soluble&#xD;
      Receptor activator of nuclear factor kappa-Β ligand ligation by osteoprotegerin down&#xD;
      regulates T-lymphocyte and dendritic activity, thereby modulating inﬂammatory responses .&#xD;
&#xD;
      Calprotectin is a group of protein heterocomplexes.These proteins are expressed mainly in&#xD;
      neutrophil and monocyte cytosols. Calprotectin stands for 60% of the circulating neutrophil&#xD;
      cytosolic proteins, and is also present in monocytes and macrophages as well as in the tissue&#xD;
      eosinophils of the ileum. Peripheral blood monocytes expose calprotectin both intra- and&#xD;
      extracellularly, but neutrophils only intracellularly. Calprotectin shows antibacterial,&#xD;
      antifungal, immunomodulatory, and antiproliferative action. Moreover, it potentially is a&#xD;
      chemotactic factor for neutrophils. Calprotectin concentration in serum increases in&#xD;
      disorders with an increase in neutrophil action. Neutrophils possess the ability to&#xD;
      transmigrate the intestinal wall; that way calprotectin may be present in the stool. It has&#xD;
      been shown that calprotectin concentration markedly increases in bowel disorders, such as&#xD;
      (Crohn's disease ulcerative Colitis, and colonic neoplasia).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">January 1, 2021</start_date>
  <completion_date type="Anticipated">January 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>level of Osteoprotegerin and sRANKL in newly diagnosed patients with inflammatory bowel disease</measure>
    <time_frame>2 years</time_frame>
    <description>measuring level of Osteoprotegerin and sRANKL in newly diagnosed patients with inflammatory bowel disease then it will measured again after treated with infliximab</description>
  </primary_outcome>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Osteoprotegerin marker in serum in inflammatory bowel disease</intervention_name>
    <description>I will measure Osteoprotegerin and Soluble Receptor activator of nuclear factor kappa-Β ligand markers in serum of patient with inflammatory bowel disease</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      serum specimen from patient with inflammatory bowel disease after diagnosis and healthy&#xD;
      persons .second sample taking 3month after received treatment&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        After standardized work-up with clinical, endoscopic, histopathologicial and, when&#xD;
        applicable, radiological evaluation, all patients will met the generally accepted&#xD;
        international diagnostic criteria of inflamatory bowel diseaes .The healthy controls&#xD;
        consisted of an age- and gender-matched (negative for IBD). This group did not show&#xD;
        evidence or familial history of IBD or any other immune mediated disorders&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly diagnosed patients (untreated) by clinical and endoscopic examination and not&#xD;
             received treatment .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients have autoimmune diseases&#xD;
&#xD;
          -  patients with cancer&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>nesma gamal, demonstrator</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>ragaa salama, professor</last_name>
    <phone>01063492008</phone>
    <email>ragaa_2002@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Amira Abdel Hamid Kamal Mohamed</last_name>
    <phone>01068345861</phone>
    <email>Amira_Kamel222@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Assuit Medical University</name>
      <address>
        <city>Assiut</city>
        <country>Egypt</country>
      </address>
    </facility>
    <contact>
      <last_name>nesma gamal, demonsterator</last_name>
      <phone>0</phone>
      <email>nesmagamal1@yahoo.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Assuit Medical University</name>
      <address>
        <city>Assiut</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 7, 2019</study_first_posted>
  <last_update_submitted>May 8, 2020</last_update_submitted>
  <last_update_submitted_qc>May 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Nesma Gamal</investigator_full_name>
    <investigator_title>principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</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/NCT03833310
org study id: vosrd
nct id: NCT03833310
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The inflammatory bowel diseases represent a heterogeneous group of chronic , relapsing-
      inflammatory disorders of the gastrointestinal tract. Crohn's disease and ulcerative colitis
      are the two major clinical forms.The global incidence and prevalence of the inflammatory
      bowel diseases has increased over the last 2-4 decades . Despite the great progress in
      understanding the pathogenesis of these diseases, their etiology remains unclear .
      Considerable effort has been devoted to the development of an accurate ,noninvasive
      biomarkers that have increased diagnostic sensitivity and specificity .

      Osteoprotegerin is a member of the Tumor Necrosis Factor Receptor superfamily of proteins.
      Osteoprotegerin is of particular importance in bone metabolism, inflammation , tumorigenesis,
      and other processes where cell differentiation, survival, and death are controlled.
      Osteoprotegerin activates inflammation in the gut by stimulating immune cells, cytokines, and
      the Necrosis factor-κappaB pathway .

      Soluble Receptor activator of nuclear factor kappa-Β ligand is known as a type II membrane
      protein and as a member of tumor necrosis factor superfamily . Soluble Receptor activator of
      nuclear factor kappa-Β ligand has been identified to affect the immune system and a binding
      partner of ( Osteoprotegerin ), and controls cell proliferation.The interactions between
      Osteoprotegerin and Soluble Receptor activator of nuclear factor kappa-Β ligand, Soluble
      Receptor activator of nuclear factor kappa-Β have relevance to inflammatory pathways. Soluble
      Receptor activator of nuclear factor kappa-Β ligand- Soluble Receptor activator of nuclear
      factor kappa-Β ligand binding activates pathways that contribute to the survival of
      T-lymphocytes and dendritic cells .
The inflammatory bowel diseases represent a heterogeneous group of chronic ,
      relapsing-remitting inflammatory disorders of the gastrointestinal tract, and Crohn's disease
      and ulcerative colitis are among the two major clinical forms The global incidence and
      prevalence of The inflammatory bowel diseases has increased over the last 2-4 decades, likely
      because of the adoption of a more "western" lifestyle as well as improved detection and
      awareness . Despite the great progress in understanding the pathogenesis of these diseases,
      their etiology remains unclear. Genetic, immune, and environmental factors are thought to
      play a key role .

      In the case of Crohn's disease , chronic inﬂammation can be localized in every
      gastrointestinal tract segment and involves the full thickness of the intestinal wall. In
      contrast ,in ulcerative colitis , mucosa and submucosa membranes of the large intestine are
      usually involved The illness starts in the rectum and generally extends proximally through
      the whole colon. . Both diseases differ in the localization and size of the segment involved.
      There are also differences in clinical image, laboratory test results, and different
      characteristics of complications. The course and grade of disease activity depend on many
      factors, such as environmental influences , genetic features, changes in the intestinal
      microbiota ecosystem, and immune factors .

      The correct diagnosis of non-specific inflammatory bowel diseases as well as the
      determination of disease activity, risk stratification , and prediction of response to
      therapy still relies on a multidisciplinary approach based on clinical, laboratory,
      endoscopic, and histologic examination . However, considerable effort has been devoted to the
      development of an accurate panel of noninvasive bio markers that have increased diagnostic
      sensitivity and specificity .

      Osteoprotegerin , also known as is a member of the Tumor Necrosis Factor Receptor superfamily
      of proteins. Osteoprotegerin is involved in many biological processes: its role is of
      particular importance in bone metabolism, inflammation , tumorigenesis, and other processes
      where cell differentiation, survival, and death are controlled. Osteoprotegerin was detected
      in serum, mucosal biopsies, and in the stool .

      The Osteoprotegerin gene is located on chromosome 8q23- 24.17. The mature OPG protein
      contains 380 amino acids and consists of seven domains. The ﬁrst four domains (D1-D4) contain
      cysteine-rich structures at the N terminus which are required for the inhibition of
      osteoclast differentiation. The ﬁfth and the sixth domain (D5 and D6) are death-domains and
      may be important in cytotoxic signals. The seventh domain, a C terminus heparin-binding site,
      is involved in dimer osteoprotegerin formation .

      Osteoprotegerin can be produced by a wide range of cell types, including osteoblasts, B
      lymphocytes, dendritic cells, bone marrow stromal cells, epithelial cells, and
      monocytes/macrophages. Osteoprotegerin activates and/or perpetuates inflammation in the gut
      by stimulating immune cells, cytokines, and the Necrosis factor-kappa B pathway .

      On the other hand, soluble Receptor activator of nuclear factor kappa-Β ligand , also known
      as tumor necrosis factor ligand. soluble Receptor activator of nuclear factor kappa-Β ligand
      is known as a type II membrane protein and as a member of tumor necrosis factor superfamily.

      Soluble Receptor activator of nuclear factor kappa-Β ligand has been identified to affect the
      immune system and control bone regeneration and remodeling, a binding partner of , and
      controls cell proliferation. it is expressed in several tissues and organs including:
      skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoblast, mammary
      gland epithelial cells, prostate and pancreas. Variation in concentration levels of soluble
      Receptor activator of nuclear factor kappa-Β ligand throughout several organs reconfirms the
      importance of in tissue soluble Receptor activator of nuclear factor kappa-Β ligand growth
      (particularly bone growth) and immune functions within the body .

      The interactions between ,Osteoprotegerin,soluble Receptor activator of nuclear factor
      kappa-Β ligand and soluble Receptor activator of nuclear factor kappa-Β also have relevance
      to inflammatory pathways. - soluble binding Receptor activator of nuclear factor kappa-Β
      binding activates several pathways that contribute to the survival of T-lymphocytes and
      dendritic cells .

      In addition, Osteoprotegerin is synthesized by dendritic and B-lymphocytes whereas soluble
      Receptor activator of nuclear factor kappa-Β ligand is mainly produced by T-lymphocytes.
      Moreover, soluble Receptor activator of nuclear factor kappa-Β ligand and various cytokines
      e.g. Tumor Necrosis Factor α induce the synthesis of osteoprotegerin from immune cells. In
      turn, the interruption of soluble Receptor activator of nuclear factor kappa-Β - soluble
      Receptor activator of nuclear factor kappa-Β ligand ligation by osteoprotegerin down
      regulates T-lymphocyte and dendritic activity, thereby modulating inﬂammatory responses .

      Calprotectin is a group of protein heterocomplexes.These proteins are expressed mainly in
      neutrophil and monocyte cytosols. Calprotectin stands for 60% of the circulating neutrophil
      cytosolic proteins, and is also present in monocytes and macrophages as well as in the tissue
      eosinophils of the ileum. Peripheral blood monocytes expose calprotectin both intra- and
      extracellularly, but neutrophils only intracellularly. Calprotectin shows antibacterial,
      antifungal, immunomodulatory, and antiproliferative action. Moreover, it potentially is a
      chemotactic factor for neutrophils. Calprotectin concentration in serum increases in
      disorders with an increase in neutrophil action. Neutrophils possess the ability to
      transmigrate the intestinal wall; that way calprotectin may be present in the stool. It has
      been shown that calprotectin concentration markedly increases in bowel disorders, such as
      (Crohn's disease ulcerative Colitis, and colonic neoplasia).
observational model: Case-Control
time perspective: Prospective
measure: level of Osteoprotegerin and sRANKL in newly diagnosed patients with inflammatory bowel disease
time frame: 2 years
description: measuring level of Osteoprotegerin and sRANKL in newly diagnosed patients with inflammatory bowel disease then it will measured again after treated with infliximab
intervention type: Diagnostic Test
intervention name: Osteoprotegerin marker in serum in inflammatory bowel disease
description: I will measure Osteoprotegerin and Soluble Receptor activator of nuclear factor kappa-Β ligand markers in serum of patient with inflammatory bowel disease
serum specimen from patient with inflammatory bowel disease after diagnosis and healthy
      persons .second sample taking 3month after received treatment
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 15 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: nesma gamal, demonstrator
role: Principal Investigator
affiliation: Assiut University
last name: ragaa salama, professor
phone: 01063492008
email: ragaa_2002@yahoo.com
last name: Amira Abdel Hamid Kamal Mohamed
phone: 01068345861
email: Amira_Kamel222@yahoo.com
facility: 
contact: 
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Nesma Gamal
investigator title: principal investigator
mesh term: Intestinal Diseases
mesh term: Inflammatory Bowel Diseases