xml: <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/NCT06032325</url>
    </required_header>
    <id_info>
      <org_study_id>1010</org_study_id>
      <nct_id>NCT06032325</nct_id>
    </id_info>
    <brief_title>Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 As Biomarkers of AKI in Children With DKA</brief_title>
    <acronym>AKI</acronym>
    <official_title>Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 As Biomarkers of Acute Kidney Injury in Children With Diabetic Ketoacidosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Assiut University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Assiut 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>
        Type 1 diabetes mellitus (T1DM) is a common, chronic, metabolic disorder that has significant&#xD;
        consequences for physical and emotional development . The incidence of TIDM is steadily&#xD;
        increasing in nearly all parts of the world by about 2-5% per year . Diabetic ketoacidosis&#xD;
        (DKA) is the most serious complication of TIDM and results from metabolic abnormalities due&#xD;
        to a severe deficiency of insulin or insulin effectiveness. Similar to diabetes, DKA has an&#xD;
        increasing incidence and more frequently occurs in children.&#xD;
  &#xD;
        DKA occurs in 20-40% of children with new-onset diabetes and in children with known diabetes&#xD;
        who omit insulin doses or who do not successfully manage during intercurrent illness (1).&#xD;
        Although the inpatient mortality rates of DKA are generally very low (5, 6) ,DKA is the&#xD;
        leading with TIDM (7). DKA is associated with numerous acid-base, hydration and electrolyte&#xD;
        derangements. Accompanied by both volume depletion and subsequent massive fluid-rehydration&#xD;
        treatment upon presentation, children with DKA potentially have a high risk for acute kidney&#xD;
        injury (AKI). For decades, nonconsensual definitions of AKI were used, making it difficult to&#xD;
        obtain an accurate evaluation of the epidemiological studies&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Type 1 diabetes mellitus (T1DM) is a common, chronic, metabolic disorder that has significant&#xD;
        consequences for physical and emotional development. The incidence of TIDM is steadily&#xD;
        increasing in nearly all parts of the world by about 2-5% per year. Diabetic ketoacidosis&#xD;
        (DKA) is the most serious complication of TIDM and results from metabolic abnormalities due&#xD;
        to a severe deficiency of insulin or insulin effectiveness. Similar to diabetes, DKA has an&#xD;
        increasing incidence and more frequently occurs in children .&#xD;
  &#xD;
        DKA occurs in 20-40% of children with new-onset diabetes and in children with known diabetes&#xD;
        who omit insulin doses or who do not successfully manage during intercurrent illness .&#xD;
        Although the inpatient mortality rates of DKA are generally very low ,DKA is the leading with&#xD;
        TIDM. DKA is associated with numerous acid-base, hydration and electrolyte derangements.&#xD;
        Accompanied by both volume depletion and subsequent massive fluid-rehydration treatment upon&#xD;
        presentation, children with DKA potentially have a high risk for acute kidney injury (AKI).&#xD;
        For decades, nonconsensual definitions of AKI were used, making it difficult to obtain an&#xD;
        accurate evaluation of the epidemiological studies During the last decade, three definitions&#xD;
        of AKI have been developed, and it is now possible to identify patients at high risk of AKI.&#xD;
        A recent study revealed that a high proportion of children with DKA develop AKI. However, AKI&#xD;
        remains poorly reported in children with DKA . Therefore, this study aimed to investigate the&#xD;
        clinical characteristics and risk factors for AKI in children with DKA, and to find the risk&#xD;
        factors of AKI on admission.&#xD;
  &#xD;
        Diabetic kidney disease (DKD) is the leading cause of end-stage kidneydisease (ESKD) and&#xD;
        dialysis in the developed world. DKD is characterizednot only by glomerular disease but also&#xD;
        tubulointerstitial injury with tubular basement membrane thickening, tubular&#xD;
        hypertrophy,epithelial-mesenchymal transition, glycogen accumulation andinterstitial&#xD;
        inflammation. Although glomerular changes in diabeteshave received significant attention from&#xD;
        researchers and clinicians,tubulointerstitial injury is known to better associate with kidney&#xD;
        dysfunction. In fact, tubular proteinuria may precede microalbuminuriain type 1 diabetes&#xD;
        (T1D), suggesting that tubular damage may be anearly injury pattern of DKD.4 High glucose&#xD;
        states, such as DKA, havebeen shown to induce proximal tubular degeneration and&#xD;
        interstitialfibrosis in both mice and humans.&#xD;
  &#xD;
        More than one third of T1D youth enrolled in the SEARCH forDiabetes in Youth study had&#xD;
        diabetic ketoacidosis (DKA) at diagnosisand in another Colorado-based study, about 55% of&#xD;
        youth with newdiagnosis of T1D presented with DKA, which is more frequent thanwhat has been&#xD;
        reported in international registries. Although acutekidney injury (AKI) secondary to&#xD;
        dehydration is a well-recognizedcomplication of DKA, tubular injury attributed to DKA is&#xD;
        poorlydescribed.5 Pathophysiologic pathways in early DKD are thought toinvolve elevated serum&#xD;
        uric acid (SUA) and vasopressin, which are also implicated in DKA. Indeed, elevated SUA and&#xD;
        vasopressin concentrationshave both shown to induce tubulointerstitial injury.&#xD;
  &#xD;
        If DKA at diagnosis of T1D in youth is associated withtubulopathy, interventions that&#xD;
        preserve tubular health may mitigatekidney damage. Targeted early interventions are&#xD;
        especially importantas development of tubular injury may confer increased risk of&#xD;
        chronickidney disease (CKD) and ESKD in the setting of DKA and AKI.&#xD;
  &#xD;
        Accordingly, our study sought to assess the extent of tubular injury in DKA by characterizing&#xD;
        the trajectories of tubular injury biomarkersover 3 months in youth with T1D diagnosed with&#xD;
        DKA and to examinethe relationship of vasopressin and SUA in the hypothesized tubularinjury.&#xD;
        Acute kidney injury is usually diagnosed with serialmeasurements of creatinine, cystatin C&#xD;
        and estimated glomerular filtrationrate (eGFR) Since these parameters are influenced by&#xD;
        iatrogenicfactors relevant to DKA care (e.g., intravenous hydration andinsulin) and are not&#xD;
        specific for tubulointerstitial injury, we also measuredthe following tubular injury markers:&#xD;
        neutrophil gelatinaseassociatedlipocalin (NGAL), kidney injury molecule 1 (KIM-1),chitinase&#xD;
        3-like 1 (YKL-40), interleukin 18 (IL-18), and monocytechemoattractant protein-1 (MCP-1).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">December 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 1, 2024</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Other</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <target_duration>1 Month</target_duration>
    <primary_outcome>
      <measure>biomarkers</measure>
      <time_frame>1 years</time_frame>
      <description>To assess Neutrophil Gelatinase associated Lipocalin and Kidney Injury Molecule-1 as biomarkers of acute kidney injury in children with Diabetic Ketoacidosis</description>
    </primary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">48</enrollment>
    <condition>Diabetes Mellitius</condition>
    <arm_group>
      <arm_group_label>Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1</arm_group_label>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Neutrophil Gelatinase and Kidney Injury Molecule-1</intervention_name>
      <description>To assess Neutrophil Gelatinase associated Lipocalin and Kidney Injury Molecule-1 as biomarkers of acute kidney injury in children with Diabetic Ketoacidosis</description>
      <arm_group_label>Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          - All patients with diabetic ketoacidosis below 18 years&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  All patients with diabetic ketoacidosis below 18 years whether first time or recurrent&#xD;
               ketoacidosis with either increase in serum creatinine more than or equal 0.3 mg/dl&#xD;
               within 48hrs or to more than or equal 1.5 times or more baseline within 7 days or&#xD;
               urine output less than 0.5 mL/kg/h for 6 hours.(22)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with known renal disease before first attack of diabetic ketoacidosis&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Year</minimum_age>
      <maximum_age>18 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <link>
      <url>https://pubmed.ncbi.nlm.nih.gov/26049401/</url>
      <description>Related Info</description>
    </link>
    <reference>
      <citation>Bjornstad P, Lanaspa MA, Ishimoto T, Kosugi T, Kume S, Jalal D, Maahs DM, Snell-Bergeon JK, Johnson RJ, Nakagawa T. Fructose and uric acid in diabetic nephropathy. Diabetologia. 2015 Sep;58(9):1993-2002. doi: 10.1007/s00125-015-3650-4. Epub 2015 Jun 7.</citation>
      <PMID>26049401</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 22, 2023</study_first_submitted>
    <study_first_submitted_qc>September 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Assiut University</investigator_affiliation>
      <investigator_full_name>Bassem Eldaba Hosny Fares</investigator_full_name>
      <investigator_title>resident</investigator_title>
    </responsible_party>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 As Biomarkers of AKI in Children With DKA</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06032325
  org study id: 1010
  nct id: NCT06032325
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Type 1 diabetes mellitus (T1DM) is a common, chronic, metabolic disorder that has significant
        consequences for physical and emotional development . The incidence of TIDM is steadily
        increasing in nearly all parts of the world by about 2-5% per year . Diabetic ketoacidosis
        (DKA) is the most serious complication of TIDM and results from metabolic abnormalities due
        to a severe deficiency of insulin or insulin effectiveness. Similar to diabetes, DKA has an
        increasing incidence and more frequently occurs in children.
  
        DKA occurs in 20-40% of children with new-onset diabetes and in children with known diabetes
        who omit insulin doses or who do not successfully manage during intercurrent illness (1).
        Although the inpatient mortality rates of DKA are generally very low (5, 6) ,DKA is the
        leading with TIDM (7). DKA is associated with numerous acid-base, hydration and electrolyte
        derangements. Accompanied by both volume depletion and subsequent massive fluid-rehydration
        treatment upon presentation, children with DKA potentially have a high risk for acute kidney
        injury (AKI). For decades, nonconsensual definitions of AKI were used, making it difficult to
        obtain an accurate evaluation of the epidemiological studies
  Type 1 diabetes mellitus (T1DM) is a common, chronic, metabolic disorder that has significant
        consequences for physical and emotional development. The incidence of TIDM is steadily
        increasing in nearly all parts of the world by about 2-5% per year. Diabetic ketoacidosis
        (DKA) is the most serious complication of TIDM and results from metabolic abnormalities due
        to a severe deficiency of insulin or insulin effectiveness. Similar to diabetes, DKA has an
        increasing incidence and more frequently occurs in children .
  
        DKA occurs in 20-40% of children with new-onset diabetes and in children with known diabetes
        who omit insulin doses or who do not successfully manage during intercurrent illness .
        Although the inpatient mortality rates of DKA are generally very low ,DKA is the leading with
        TIDM. DKA is associated with numerous acid-base, hydration and electrolyte derangements.
        Accompanied by both volume depletion and subsequent massive fluid-rehydration treatment upon
        presentation, children with DKA potentially have a high risk for acute kidney injury (AKI).
        For decades, nonconsensual definitions of AKI were used, making it difficult to obtain an
        accurate evaluation of the epidemiological studies During the last decade, three definitions
        of AKI have been developed, and it is now possible to identify patients at high risk of AKI.
        A recent study revealed that a high proportion of children with DKA develop AKI. However, AKI
        remains poorly reported in children with DKA . Therefore, this study aimed to investigate the
        clinical characteristics and risk factors for AKI in children with DKA, and to find the risk
        factors of AKI on admission.
  
        Diabetic kidney disease (DKD) is the leading cause of end-stage kidneydisease (ESKD) and
        dialysis in the developed world. DKD is characterizednot only by glomerular disease but also
        tubulointerstitial injury with tubular basement membrane thickening, tubular
        hypertrophy,epithelial-mesenchymal transition, glycogen accumulation andinterstitial
        inflammation. Although glomerular changes in diabeteshave received significant attention from
        researchers and clinicians,tubulointerstitial injury is known to better associate with kidney
        dysfunction. In fact, tubular proteinuria may precede microalbuminuriain type 1 diabetes
        (T1D), suggesting that tubular damage may be anearly injury pattern of DKD.4 High glucose
        states, such as DKA, havebeen shown to induce proximal tubular degeneration and
        interstitialfibrosis in both mice and humans.
  
        More than one third of T1D youth enrolled in the SEARCH forDiabetes in Youth study had
        diabetic ketoacidosis (DKA) at diagnosisand in another Colorado-based study, about 55% of
        youth with newdiagnosis of T1D presented with DKA, which is more frequent thanwhat has been
        reported in international registries. Although acutekidney injury (AKI) secondary to
        dehydration is a well-recognizedcomplication of DKA, tubular injury attributed to DKA is
        poorlydescribed.5 Pathophysiologic pathways in early DKD are thought toinvolve elevated serum
        uric acid (SUA) and vasopressin, which are also implicated in DKA. Indeed, elevated SUA and
        vasopressin concentrationshave both shown to induce tubulointerstitial injury.
  
        If DKA at diagnosis of T1D in youth is associated withtubulopathy, interventions that
        preserve tubular health may mitigatekidney damage. Targeted early interventions are
        especially importantas development of tubular injury may confer increased risk of
        chronickidney disease (CKD) and ESKD in the setting of DKA and AKI.
  
        Accordingly, our study sought to assess the extent of tubular injury in DKA by characterizing
        the trajectories of tubular injury biomarkersover 3 months in youth with T1D diagnosed with
        DKA and to examinethe relationship of vasopressin and SUA in the hypothesized tubularinjury.
        Acute kidney injury is usually diagnosed with serialmeasurements of creatinine, cystatin C
        and estimated glomerular filtrationrate (eGFR) Since these parameters are influenced by
        iatrogenicfactors relevant to DKA care (e.g., intravenous hydration andinsulin) and are not
        specific for tubulointerstitial injury, we also measuredthe following tubular injury markers:
        neutrophil gelatinaseassociatedlipocalin (NGAL), kidney injury molecule 1 (KIM-1),chitinase
        3-like 1 (YKL-40), interleukin 18 (IL-18), and monocytechemoattractant protein-1 (MCP-1).
  observational model: Other
  time perspective: Prospective
  measure: biomarkers
  time frame: 1 years
  description: To assess Neutrophil Gelatinase associated Lipocalin and Kidney Injury Molecule-1 as biomarkers of acute kidney injury in children with Diabetic Ketoacidosis
  arm group label: Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1
  intervention type: Diagnostic Test
  intervention name: Neutrophil Gelatinase and Kidney Injury Molecule-1
  description: To assess Neutrophil Gelatinase associated Lipocalin and Kidney Injury Molecule-1 as biomarkers of acute kidney injury in children with Diabetic Ketoacidosis
  arm group label: Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 1 Year
  maximum age: 18 Years
  healthy volunteers: No
  url: https://pubmed.ncbi.nlm.nih.gov/26049401/
  description: Related Info
  citation: Bjornstad P, Lanaspa MA, Ishimoto T, Kosugi T, Kume S, Jalal D, Maahs DM, Snell-Bergeon JK, Johnson RJ, Nakagawa T. Fructose and uric acid in diabetic nephropathy. Diabetologia. 2015 Sep;58(9):1993-2002. doi: 10.1007/s00125-015-3650-4. Epub 2015 Jun 7.
  PMID: 26049401
  responsible party type: Principal Investigator
  investigator affiliation: Assiut University
  investigator full name: Bassem Eldaba Hosny Fares
  investigator title: resident
  sharing ipd: No
  ipd description: Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 As Biomarkers of AKI in Children With DKA