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/NCT06006468</url>
    </required_header>
    <id_info>
      <org_study_id>CRF525</org_study_id>
      <nct_id>NCT06006468</nct_id>
    </id_info>
    <brief_title>Evaluating ImmuNe Changes in the Evolution of Pre Type 1 Diabetes With Adult ONset</brief_title>
    <acronym>INCEPTiON</acronym>
    <official_title>Evaluating ImmuNe Changes in the Evolution of Pre Type 1 Diabetes With Adult Onset</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Royal Devon and Exeter NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Exeter</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Royal Devon and Exeter NHS Foundation Trust</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>
        Little is known about how type 1 diabetes or coeliac disease develop in adults. Studies&#xD;
        following children at risk of type 1 diabetes from birth have shown that the marker of type 1&#xD;
        diabetes autoimmunity (antibodies against the insulin producing cells in the pancreas&#xD;
        (Glutamic Acid Decarboxylase Autoantibodies (GADA), Insulin Autoantibodies (IAA), Zinc&#xD;
        Transporter 8 Autoantibodies (ZnT8), Anti-tyrosine phosphatase-like insulinoma antigen 2&#xD;
        (IA-2))) can develop many years before glucose levels are raised and diabetes is diagnosed.&#xD;
        In adults, it is unclear when antibodies develop in relation to high blood glucose levels and&#xD;
        the diagnosis of type 1 diabetes.&#xD;
  &#xD;
        Similarly in coeliac disease it is unclear to what degree Tissue transglutaminase&#xD;
        autoantibodies (TTG) in adults proceed the development of clinically diagnosed disease.&#xD;
  &#xD;
        The investigators will use samples collected and stored in The Exeter 10,000 volunteer&#xD;
        research bank (https://exetercrfnihr.org/about/exeter-10000/) and so no new sample collection&#xD;
        is required. This includes ~8000 participants with no history of coeliac disease or diabetes&#xD;
        at recruitment. The investigators wish to determine prevalence of autoantibodies in the&#xD;
        background adult population split by the highest genetic risk for type 1 diabetes and&#xD;
        separately coeliac disease compared to a control population with lower genetic risk for these&#xD;
        conditions. The investigators will also evaluate the proportion of these identified cases&#xD;
        progressing to clinically diagnosed disease.&#xD;
  &#xD;
        The aim of this study is to investigate evidence of autoimmunity prior to disease development&#xD;
        and generate pilot data for the validity of screening based on genetic predisposition for&#xD;
        type 1 diabetes and coeliac disease.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Detecting the early stages of type 1 diabetes in children is possible and has positive&#xD;
        implications for clinical care.&#xD;
  &#xD;
        Studies following children at risk of type 1 diabetes from birth have shown that islet&#xD;
        autoantibodies against (Glutamic Acid Decarboxylase (GADA), Insulin (IAA), Zinc Transporter 8&#xD;
        (ZnT8), Anti-tyrosine phosphatase-like insulinoma antigen 2 (IA-2))) can develop many years&#xD;
        before diabetes is diagnosed. This makes islet-autoantibodies an excellent biomarker of early&#xD;
        disease with the development of multiple (≥2) positive islet-autoantibodies marking the first&#xD;
        stage of type 1 diabetes. Many studies in children have looked at strategies for increasing&#xD;
        islet autoantibody detection given the high numbers needed to test if screening at the whole&#xD;
        population level. This includes targeting for autoantibody testing those with a type 1&#xD;
        diabetes: family history and/or raised genetic risk. Identifying type 1 diabetes early&#xD;
        matters as it can reduce the proportion of cases presenting with severe symptoms including&#xD;
        with diabetic ketoacidosis. This is coupled to recent FDA approval of Teplizumab therapy&#xD;
        aiming to slow down the progression of early type 1 diabetes.&#xD;
  &#xD;
        Little is known about the early development or early case detection of type 1 diabetes in&#xD;
        adults despite representing the majority of all cases. Despite the potential benefits of&#xD;
        pre-clinical type 1 diabetes detection in children very little is known about the stages of&#xD;
        development of type 1 diabetes in adults. Therefore as noted in a recent Type 1 Diabetes&#xD;
        research Steering Committee meeting &quot;The optimal strategies for identification of at-risk&#xD;
        adults needs to be studied&quot;. This is despite over half of all type 1 diabetes cases&#xD;
        developing in adults. Our recent work examining adult-onset type 1 diabetes at presentation&#xD;
        suggests that when adult-onset type 1 diabetes cases are defined robustly, characteristics&#xD;
        include high type 1 diabetes genetic risk, rapid progression of C-peptide loss and high&#xD;
        (&gt;90%) rates of islet autoantibody positivity. Of these adult autoantibody positive cases&#xD;
        ~60% were multi-autoantibody positive. Previous literature suggesting type 1 diabetes is a&#xD;
        more benign disease in older adults likely reflects the increasingly recognised&#xD;
        misclassification of clinically defined type 1 diabetes cases in this age group.&#xD;
  &#xD;
        The high rates of islet autoantibodies at diagnosis and associated high genetic risk in&#xD;
        adult-onset type 1 diabetes cases suggests targeted screening for early disease in this age&#xD;
        group, using these biomarkers as undertaken in children, is a possibility. Studies recruiting&#xD;
        first degree relatives of individuals have included adults (typically up to 45 years of age)&#xD;
        showing detection of individuals at risk of type 1 diabetes is possible, even if progression&#xD;
        from stage 1 to clinical disease appears reduced with increasing age at autoantibody&#xD;
        detection. However, as in children, the majority of type 1 diabetes cases in adults develop&#xD;
        in those without a family history of the disease and therefore genetic risk guided screening&#xD;
        offers an attractive alternative strategy but research into the validity of this approach is&#xD;
        lacking.&#xD;
  &#xD;
        Little is known about early Coeliac disease development in adults. Coeliac disease is&#xD;
        similarly increasingly recognised in adults but the early development of the disease is&#xD;
        unclear. Development of coeliac disease is associated with raised genetic risk which can be&#xD;
        captured by a coeliac genetic risk score. Recognition of coeliac disease is difficult&#xD;
        particularly in adults and early detection has been suggested to be associated with improved&#xD;
        outcomes.&#xD;
  &#xD;
        Datasets with genetics and stored samples allow pragmatic insights into the feasibility of&#xD;
        targeted screening for early adult-onset type 1 diabetes and coeliac disease.&#xD;
  &#xD;
        The investigators will use samples collected and stored in The Exeter 10,000 adult volunteer&#xD;
        research bank (https://exetercrfnihr.org/about/exeter-10000/) which includes ∼8000&#xD;
        participants with no history of diabetes at recruitment (a median 10 years ago (minimum 3&#xD;
        years since recruitment)). This will allow islet autoantibody measurement without the need&#xD;
        for additional sample collection. All participants have genotype data available and have&#xD;
        given permission for the Exeter 10,000 team to prospectively access their health records.&#xD;
        This dataset allows a pragmatic and cost-effective assessment of using genetic predisposition&#xD;
        to type 1 diabetes and coeliac disease to guide islet-autoantibody/ tissue-transglutaminase&#xD;
        testing in adults. This will provide vital pilot data which can help guide future screening&#xD;
        strategies for detecting pre-clinical type 1 diabetes and coeliac disease in adults.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">February 1, 2023</start_date>
    <completion_date type="Anticipated">December 2023</completion_date>
    <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Other</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Number of multi-islet autoantibody positive participants</measure>
      <time_frame>through sample analysis, approx 6 months</time_frame>
      <description>≥2 positive islet autoantibodies (GAD, IA-2, ZNT8, IAA) between genetic risk groups for type 1 diabetes</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of islet autoantibody positive participants</measure>
      <time_frame>through sample analysis, approx 6 months</time_frame>
      <description>≥1 positive islet autoantibodies (GAD, IA-2, ZNT8, IAA) between genetic risk groups for type 1 diabetes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of multi-islet autoantibody positive participants developing Diabetes</measure>
      <time_frame>through study follow up an average of 10 years</time_frame>
      <description>number of cases developing type 1 diabetes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with positive Tissue transglutaminase autoantibodies</measure>
      <time_frame>through sample analysis, approx 6 months</time_frame>
      <description>Number of positive Tissue transglutaminase autoantibody in genetic risk groups for coeliac disease</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants developing Coeliac disease</measure>
      <time_frame>through study follow up an average of 10 years</time_frame>
      <description>number of cases developing Coeliac disease</description>
    </secondary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Actual">2250</enrollment>
    <condition>Type 1 Diabetes</condition>
    <condition>Type 1 Diabetes Mellitus Maturity Onset</condition>
    <arm_group>
      <arm_group_label>Genetic risk of Type 1 diabetes</arm_group_label>
      <description>750 individuals with the highest type 1 diabetes genetic risk</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Genetic risk of coeliac disease</arm_group_label>
      <description>750 individuals with the highest coeliac disease genetic risk</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Controls</arm_group_label>
      <description>750 individuals with Neutral type 1 diabetes and coeliac disease genetic risk</description>
    </arm_group>
    <intervention>
      <intervention_type>Genetic</intervention_type>
      <intervention_name>High genetic risk for type 1 diabetes</intervention_name>
      <description>in individuals without diabetes comparison of prevalence of islet auto antibodies between individuals at high genetic risk of type 1 diabetes versus controls</description>
      <arm_group_label>Controls</arm_group_label>
      <arm_group_label>Genetic risk of Type 1 diabetes</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Genetic</intervention_type>
      <intervention_name>High gentic risk for Coeliac disease</intervention_name>
      <description>in individuals without Coeliac disease comparison of prevalence of anti tissue transglutaminase antibodies between individuals at high genetic risk of coeliac disease versus controls</description>
      <arm_group_label>Controls</arm_group_label>
      <arm_group_label>Genetic risk of coeliac disease</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          This study will use samples and data from the Exeter 10,000 cohort, a research bank of&#xD;
          adult volunteers (https://exetercrfnihr.org/about/exeter-10000/). Stored serum samples are&#xD;
          available (allowing islet autoantibody measurement) for all participants including ∼8000&#xD;
          participants with no history of diabetes at recruitment (a median 10 years ago (minimum 3&#xD;
          years since recruitment)). Additionally all participants have genotype data available and&#xD;
          have given permission to the research team to prospectively access their health records.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Exeter 10,000 study participants with stored serum samples&#xD;
  &#xD;
            -  Consent for samples &amp; data to be used in further research.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Diagnosed with diabetes at time of original sample collection&#xD;
  &#xD;
            -  Diagnosed with coeliac disease at time of original sample collection&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Richard Oram, Dr</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Exeter &amp; Royal Devon University Healthcare NHS Foundation Trust</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>NIHR Exeter Clinical Research Facility (Royal Devon University Healthcare NHS Foundation Trust)</name>
        <address>
          <city>Exeter</city>
          <state>Devon</state>
          <zip>EX2 5DW</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
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    <verification_date>February 2023</verification_date>
    <study_first_submitted>June 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Diabetes Mellitus</mesh_term>
      <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
      <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Extend data available through external application process to university of Exeter</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/NCT06006468
  org study id: CRF525
  nct id: NCT06006468
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Little is known about how type 1 diabetes or coeliac disease develop in adults. Studies
        following children at risk of type 1 diabetes from birth have shown that the marker of type 1
        diabetes autoimmunity (antibodies against the insulin producing cells in the pancreas
        (Glutamic Acid Decarboxylase Autoantibodies (GADA), Insulin Autoantibodies (IAA), Zinc
        Transporter 8 Autoantibodies (ZnT8), Anti-tyrosine phosphatase-like insulinoma antigen 2
        (IA-2))) can develop many years before glucose levels are raised and diabetes is diagnosed.
        In adults, it is unclear when antibodies develop in relation to high blood glucose levels and
        the diagnosis of type 1 diabetes.
  
        Similarly in coeliac disease it is unclear to what degree Tissue transglutaminase
        autoantibodies (TTG) in adults proceed the development of clinically diagnosed disease.
  
        The investigators will use samples collected and stored in The Exeter 10,000 volunteer
        research bank (https://exetercrfnihr.org/about/exeter-10000/) and so no new sample collection
        is required. This includes ~8000 participants with no history of coeliac disease or diabetes
        at recruitment. The investigators wish to determine prevalence of autoantibodies in the
        background adult population split by the highest genetic risk for type 1 diabetes and
        separately coeliac disease compared to a control population with lower genetic risk for these
        conditions. The investigators will also evaluate the proportion of these identified cases
        progressing to clinically diagnosed disease.
  
        The aim of this study is to investigate evidence of autoimmunity prior to disease development
        and generate pilot data for the validity of screening based on genetic predisposition for
        type 1 diabetes and coeliac disease.
  Detecting the early stages of type 1 diabetes in children is possible and has positive
        implications for clinical care.
  
        Studies following children at risk of type 1 diabetes from birth have shown that islet
        autoantibodies against (Glutamic Acid Decarboxylase (GADA), Insulin (IAA), Zinc Transporter 8
        (ZnT8), Anti-tyrosine phosphatase-like insulinoma antigen 2 (IA-2))) can develop many years
        before diabetes is diagnosed. This makes islet-autoantibodies an excellent biomarker of early
        disease with the development of multiple (≥2) positive islet-autoantibodies marking the first
        stage of type 1 diabetes. Many studies in children have looked at strategies for increasing
        islet autoantibody detection given the high numbers needed to test if screening at the whole
        population level. This includes targeting for autoantibody testing those with a type 1
        diabetes: family history and/or raised genetic risk. Identifying type 1 diabetes early
        matters as it can reduce the proportion of cases presenting with severe symptoms including
        with diabetic ketoacidosis. This is coupled to recent FDA approval of Teplizumab therapy
        aiming to slow down the progression of early type 1 diabetes.
  
        Little is known about the early development or early case detection of type 1 diabetes in
        adults despite representing the majority of all cases. Despite the potential benefits of
        pre-clinical type 1 diabetes detection in children very little is known about the stages of
        development of type 1 diabetes in adults. Therefore as noted in a recent Type 1 Diabetes
        research Steering Committee meeting "The optimal strategies for identification of at-risk
        adults needs to be studied". This is despite over half of all type 1 diabetes cases
        developing in adults. Our recent work examining adult-onset type 1 diabetes at presentation
        suggests that when adult-onset type 1 diabetes cases are defined robustly, characteristics
        include high type 1 diabetes genetic risk, rapid progression of C-peptide loss and high
        (>90%) rates of islet autoantibody positivity. Of these adult autoantibody positive cases
        ~60% were multi-autoantibody positive. Previous literature suggesting type 1 diabetes is a
        more benign disease in older adults likely reflects the increasingly recognised
        misclassification of clinically defined type 1 diabetes cases in this age group.
  
        The high rates of islet autoantibodies at diagnosis and associated high genetic risk in
        adult-onset type 1 diabetes cases suggests targeted screening for early disease in this age
        group, using these biomarkers as undertaken in children, is a possibility. Studies recruiting
        first degree relatives of individuals have included adults (typically up to 45 years of age)
        showing detection of individuals at risk of type 1 diabetes is possible, even if progression
        from stage 1 to clinical disease appears reduced with increasing age at autoantibody
        detection. However, as in children, the majority of type 1 diabetes cases in adults develop
        in those without a family history of the disease and therefore genetic risk guided screening
        offers an attractive alternative strategy but research into the validity of this approach is
        lacking.
  
        Little is known about early Coeliac disease development in adults. Coeliac disease is
        similarly increasingly recognised in adults but the early development of the disease is
        unclear. Development of coeliac disease is associated with raised genetic risk which can be
        captured by a coeliac genetic risk score. Recognition of coeliac disease is difficult
        particularly in adults and early detection has been suggested to be associated with improved
        outcomes.
  
        Datasets with genetics and stored samples allow pragmatic insights into the feasibility of
        targeted screening for early adult-onset type 1 diabetes and coeliac disease.
  
        The investigators will use samples collected and stored in The Exeter 10,000 adult volunteer
        research bank (https://exetercrfnihr.org/about/exeter-10000/) which includes ∼8000
        participants with no history of diabetes at recruitment (a median 10 years ago (minimum 3
        years since recruitment)). This will allow islet autoantibody measurement without the need
        for additional sample collection. All participants have genotype data available and have
        given permission for the Exeter 10,000 team to prospectively access their health records.
        This dataset allows a pragmatic and cost-effective assessment of using genetic predisposition
        to type 1 diabetes and coeliac disease to guide islet-autoantibody/ tissue-transglutaminase
        testing in adults. This will provide vital pilot data which can help guide future screening
        strategies for detecting pre-clinical type 1 diabetes and coeliac disease in adults.
  observational model: Other
  time perspective: Retrospective
  measure: Number of multi-islet autoantibody positive participants
  time frame: through sample analysis, approx 6 months
  description: ≥2 positive islet autoantibodies (GAD, IA-2, ZNT8, IAA) between genetic risk groups for type 1 diabetes
  measure: Number of islet autoantibody positive participants
  time frame: through sample analysis, approx 6 months
  description: ≥1 positive islet autoantibodies (GAD, IA-2, ZNT8, IAA) between genetic risk groups for type 1 diabetes
  measure: Number of multi-islet autoantibody positive participants developing Diabetes
  time frame: through study follow up an average of 10 years
  description: number of cases developing type 1 diabetes
  measure: Number of participants with positive Tissue transglutaminase autoantibodies
  time frame: through sample analysis, approx 6 months
  description: Number of positive Tissue transglutaminase autoantibody in genetic risk groups for coeliac disease
  measure: Number of participants developing Coeliac disease
  time frame: through study follow up an average of 10 years
  description: number of cases developing Coeliac disease
  arm group label: Genetic risk of Type 1 diabetes
  description: 750 individuals with the highest type 1 diabetes genetic risk
  arm group label: Genetic risk of coeliac disease
  description: 750 individuals with the highest coeliac disease genetic risk
  arm group label: Controls
  description: 750 individuals with Neutral type 1 diabetes and coeliac disease genetic risk
  intervention type: Genetic
  intervention name: High genetic risk for type 1 diabetes
  description: in individuals without diabetes comparison of prevalence of islet auto antibodies between individuals at high genetic risk of type 1 diabetes versus controls
  arm group label: Controls
  arm group label: Genetic risk of Type 1 diabetes
  intervention type: Genetic
  intervention name: High gentic risk for Coeliac disease
  description: in individuals without Coeliac disease comparison of prevalence of anti tissue transglutaminase antibodies between individuals at high genetic risk of coeliac disease versus controls
  arm group label: Controls
  arm group label: Genetic risk of coeliac disease
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Richard Oram, Dr
  role: Principal Investigator
  affiliation: University of Exeter & Royal Devon University Healthcare NHS Foundation Trust
  facility: 
  country: United Kingdom
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  PMID: 25665818
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  PMID: 36674702
  responsible party type: Sponsor
  mesh term: Diabetes Mellitus
  mesh term: Diabetes Mellitus, Type 1
  mesh term: Diabetes Mellitus, Type 2
  sharing ipd: No
  ipd description: Extend data available through external application process to university of Exeter