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/NCT05980221</url>
    </required_header>
    <id_info>
      <org_study_id>RRK6813</org_study_id>
      <nct_id>NCT05980221</nct_id>
    </id_info>
    <brief_title>The Development of a Metabolomic Test to Diagnose and Quantify Pancreatic Exocrine Insufficiency (The DETECTION Study)</brief_title>
    <acronym>DETECTION</acronym>
    <official_title>The Development of a Metabolomic Test to Diagnose and Quantify Pancreatic Exocrine Insufficiency (The DETECTION Study)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital Birmingham NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Pancreatic Cancer UK</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University Hospital Birmingham 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>
        DETECTION. The development of a metabolomic test to diagnose and quantify pancreatic exocrine&#xD;
        insufficiency.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Pancreatic exocrine insufficiency (PEI) is prevalent and progressive among patients with&#xD;
        pancreatic cancer, treatment with pancreatic enzyme replacement therapy (PERT) has been&#xD;
        proven to reduce gastrointestinal symptoms, improve quality of life and survival and is&#xD;
        therefore recommended in NICE guidelines. Despite this, most patients with PEI do not receive&#xD;
        PERT.&#xD;
  &#xD;
        One cause for under treatment is lack of a well-tolerated and accurate diagnostic test that&#xD;
        can provide quick results. The current, most widely used test, the faecal elastase stool&#xD;
        test, has low accuracy, particularly after surgery, and results take several days.&#xD;
        Furthermore, the test cannot help with dosing of PERT.&#xD;
  &#xD;
        Metabolomics can be used to quantify metabolites in blood. These metabolites are directly&#xD;
        influenced by normal digestion and absorption of food, for example blood lipid levels are&#xD;
        very different in the fed and fasted states. This program of work will give a standard meal&#xD;
        to healthy controls and patients with PEI and screen their blood before and after a test&#xD;
        meal. Differences in the metabolic profile will be used to develop a 'fingerprint' of PEI&#xD;
        based upon one metabolite or a combination of metabolites.&#xD;
  &#xD;
        The ultimate goal is to develop a simple blood test that can be used outside of specialist&#xD;
        centres that is acceptable to patients, can accurately diagnose PEI and can guide treatment&#xD;
        with PERT.&#xD;
  &#xD;
        This body of work aims to investigate the metabolome of patients with PEI (of different&#xD;
        causes), PEI will be defined in the different cohorts by a multimodel approach with the 13C&#xD;
        MTGT as primary reference test and FE-1 and PEI-Q used as supporting tests.&#xD;
  &#xD;
        A test meal will be given to fasted participants alongside baseline blood samples and breath&#xD;
        samples. Patients will then have blood and breath taken hourly for 6 hours. Blood samples&#xD;
        will be spun and frozen for batch metabolomic analysis.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 24, 2020</start_date>
    <completion_date type="Anticipated">October 2024</completion_date>
    <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>Investigating the metabolome of patients with PEI in the fasted and fed state. Prospective, single centre, observational study</intervention_model_description>
      <primary_purpose>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Metabolome</measure>
      <time_frame>1 year after study completion</time_frame>
      <description>metabolomic fingerprint of patient with PEI in the fed and fasted state Bloods are taken in the fed and fasted state, after centrifugation, the plasma is then frozen at -80. Samples will then be analysed using untargeted liquid chromatography mass spectrometry, after which the raw data will be processed using the open-source software XCMS. The resultant metabolite features in the samples will be compared between healthy and diseased (PEI) cohorts to identify features specific to exocrine insufficiency.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>PEI status using 13CMTGT in comparison to the metabolome</measure>
      <time_frame>1 year after study completion</time_frame>
      <description>breath test (13CMTGT). 13C labelled fatty test meal ingested, exhaled breath samples eveyr hour up to 6 hours, the cumulative percent dose of 13C recovered will then be used as a marker for PEI, diagnostic under 29%</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PEI status using FE-1 in comparison to the metabolome</measure>
      <time_frame>1 year after study completion</time_frame>
      <description>FE-1. Faecal elastase, diagnostic &lt;200</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PEI status using PEIQ in comparison to the metabolome</measure>
      <time_frame>1 year after study completion</time_frame>
      <description>PEI-Q: Pancreatic exocrine insufficiency questionnaire (symptomatic assessment of PEI). &gt;1.8 severe PEI, 1.4-1.8 moderate PEI, 0.6-1.4 mild PEI</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Response of the fed and fasted metabolome to PERT</measure>
      <time_frame>1 year after study completion</time_frame>
      <description>Investigation of the metabolome in response to PERT low dose and high dose. The metabolomic profile indicative of PEI will then be assessed in a repeat cohort of patients that reattend twice on low dose and then high dose PERT. Bloods will be taken as for the main trial, in the fed and fasted state and the metabolomic profile (determined by the main cohort) will assessed using targeted liquid chromatography mass spectrometry to investigate whether it is altered by PERT (pancreatic exocrine replacement therapy)</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Pancreatic Exocrine Insufficiency</condition>
    <arm_group>
      <arm_group_label>Pancreatic cancer (main cohort)</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>investigation of PEI and the metabolome of patients with pancreatic cancer in the fed and fasted state</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sub-study cohorts: Chronic pancreatitis, cystic fibrosis, NET patients on SSAs</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>investigation of PEI and the metabolome of patients with other causes of PEI in the fed and fasted state</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dosing arm</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Investigation metabolome of patients pre and post initiation of PERT as part of their PEI care</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Metabolomics</intervention_name>
      <description>Plasma samples taken for the investigation of the metabolome</description>
      <arm_group_label>Dosing arm</arm_group_label>
      <arm_group_label>Pancreatic cancer (main cohort)</arm_group_label>
      <arm_group_label>Sub-study cohorts: Chronic pancreatitis, cystic fibrosis, NET patients on SSAs</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>13C MTGT</intervention_name>
      <description>sequential breath samples taken for investigation of PEI (reference test)</description>
      <arm_group_label>Dosing arm</arm_group_label>
      <arm_group_label>Pancreatic cancer (main cohort)</arm_group_label>
      <arm_group_label>Sub-study cohorts: Chronic pancreatitis, cystic fibrosis, NET patients on SSAs</arm_group_label>
      <other_name>13C MTG breath test</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria: (for main pancreatic cancer cohort)&#xD;
  &#xD;
            -  PDAC&#xD;
  &#xD;
            -  PEI (as defined by breath test)&#xD;
  &#xD;
            -  Tolerating oral diet Inclusion Criteria: (for CF cohort)&#xD;
  &#xD;
            -  CF&#xD;
  &#xD;
            -  PEI (as defined by breath test)&#xD;
  &#xD;
            -  Tolerating oral diet Inclusion Criteria: (for CP cohort)&#xD;
  &#xD;
            -  CP&#xD;
  &#xD;
            -  PEI (as defined by breath test)&#xD;
  &#xD;
            -  Tolerating oral diet&#xD;
  &#xD;
          Exclusion Criteria (all arms):&#xD;
  &#xD;
            -  No other GI conditions&#xD;
  &#xD;
            -  For each arm no evidence of the other arm conditions&#xD;
  &#xD;
            -  For health controls, no history of CP, CF or pancreatic cancer&#xD;
  &#xD;
            -  No GI surgery (except pancreatic resection in the pancreatic cancer cohort)&#xD;
  &#xD;
            -  Unable to consent&#xD;
  &#xD;
            -  Unable to travel to UHB for testing&#xD;
  &#xD;
            -  Prognosis &lt; 2months&#xD;
  &#xD;
            -  Performance status 2+&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>16 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Keith Roberts, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Hospital Birmingham NHS Foundation Trust</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Sarah Powell-Brett, MBChB</last_name>
      <phone>07887754856</phone>
      <email>sarah.powell-brett1@nhs.net</email>
    </overall_contact>
    <location>
      <facility>
        <name>University Hospitals Birmingham NHS Foundation Trust</name>
        <address>
          <city>Birmingham</city>
          <country>United Kingdom</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Sarah Powell-Brett, MBChB</last_name>
        <phone>078877754856</phone>
        <email>sarah.powell-brett1@nhs.net</email>
      </contact>
      <contact_backup>
        <last_name>Keith Roberts, PhD</last_name>
        <email>keith.roberts@uhb.nhs.uk</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>May 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University Hospital Birmingham NHS Foundation Trust</investigator_affiliation>
      <investigator_full_name>Keith John Roberts</investigator_full_name>
      <investigator_title>Consultant HPB and transplant surgeon</investigator_title>
    </responsible_party>
    <keyword>exocrine insufficiency</keyword>
    <keyword>pancreatic cancer</keyword>
    <keyword>metabolomics</keyword>
    <keyword>metabolites</keyword>
    <keyword>chronic pancreatitis</keyword>
    <keyword>cystic fibrosis</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Exocrine Pancreatic Insufficiency</mesh_term>
    </condition_browse>
    <!-- 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/NCT05980221
  org study id: RRK6813
  nct id: NCT05980221
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  DETECTION. The development of a metabolomic test to diagnose and quantify pancreatic exocrine
        insufficiency.
  Pancreatic exocrine insufficiency (PEI) is prevalent and progressive among patients with
        pancreatic cancer, treatment with pancreatic enzyme replacement therapy (PERT) has been
        proven to reduce gastrointestinal symptoms, improve quality of life and survival and is
        therefore recommended in NICE guidelines. Despite this, most patients with PEI do not receive
        PERT.
  
        One cause for under treatment is lack of a well-tolerated and accurate diagnostic test that
        can provide quick results. The current, most widely used test, the faecal elastase stool
        test, has low accuracy, particularly after surgery, and results take several days.
        Furthermore, the test cannot help with dosing of PERT.
  
        Metabolomics can be used to quantify metabolites in blood. These metabolites are directly
        influenced by normal digestion and absorption of food, for example blood lipid levels are
        very different in the fed and fasted states. This program of work will give a standard meal
        to healthy controls and patients with PEI and screen their blood before and after a test
        meal. Differences in the metabolic profile will be used to develop a 'fingerprint' of PEI
        based upon one metabolite or a combination of metabolites.
  
        The ultimate goal is to develop a simple blood test that can be used outside of specialist
        centres that is acceptable to patients, can accurately diagnose PEI and can guide treatment
        with PERT.
  
        This body of work aims to investigate the metabolome of patients with PEI (of different
        causes), PEI will be defined in the different cohorts by a multimodel approach with the 13C
        MTGT as primary reference test and FE-1 and PEI-Q used as supporting tests.
  
        A test meal will be given to fasted participants alongside baseline blood samples and breath
        samples. Patients will then have blood and breath taken hourly for 6 hours. Blood samples
        will be spun and frozen for batch metabolomic analysis.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: Investigating the metabolome of patients with PEI in the fasted and fed state. Prospective, single centre, observational study
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: Metabolome
  time frame: 1 year after study completion
  description: metabolomic fingerprint of patient with PEI in the fed and fasted state Bloods are taken in the fed and fasted state, after centrifugation, the plasma is then frozen at -80. Samples will then be analysed using untargeted liquid chromatography mass spectrometry, after which the raw data will be processed using the open-source software XCMS. The resultant metabolite features in the samples will be compared between healthy and diseased (PEI) cohorts to identify features specific to exocrine insufficiency.
  measure: PEI status using 13CMTGT in comparison to the metabolome
  time frame: 1 year after study completion
  description: breath test (13CMTGT). 13C labelled fatty test meal ingested, exhaled breath samples eveyr hour up to 6 hours, the cumulative percent dose of 13C recovered will then be used as a marker for PEI, diagnostic under 29%
  measure: PEI status using FE-1 in comparison to the metabolome
  time frame: 1 year after study completion
  description: FE-1. Faecal elastase, diagnostic <200
  measure: PEI status using PEIQ in comparison to the metabolome
  time frame: 1 year after study completion
  description: PEI-Q: Pancreatic exocrine insufficiency questionnaire (symptomatic assessment of PEI). >1.8 severe PEI, 1.4-1.8 moderate PEI, 0.6-1.4 mild PEI
  measure: Response of the fed and fasted metabolome to PERT
  time frame: 1 year after study completion
  description: Investigation of the metabolome in response to PERT low dose and high dose. The metabolomic profile indicative of PEI will then be assessed in a repeat cohort of patients that reattend twice on low dose and then high dose PERT. Bloods will be taken as for the main trial, in the fed and fasted state and the metabolomic profile (determined by the main cohort) will assessed using targeted liquid chromatography mass spectrometry to investigate whether it is altered by PERT (pancreatic exocrine replacement therapy)
  arm group label: Pancreatic cancer (main cohort)
  arm group type: Other
  description: investigation of PEI and the metabolome of patients with pancreatic cancer in the fed and fasted state
  arm group label: Sub-study cohorts: Chronic pancreatitis, cystic fibrosis, NET patients on SSAs
  arm group type: Other
  description: investigation of PEI and the metabolome of patients with other causes of PEI in the fed and fasted state
  arm group label: Dosing arm
  arm group type: Other
  description: Investigation metabolome of patients pre and post initiation of PERT as part of their PEI care
  intervention type: Diagnostic Test
  intervention name: Metabolomics
  description: Plasma samples taken for the investigation of the metabolome
  arm group label: Dosing arm
  arm group label: Pancreatic cancer (main cohort)
  arm group label: Sub-study cohorts: Chronic pancreatitis, cystic fibrosis, NET patients on SSAs
  intervention type: Diagnostic Test
  intervention name: 13C MTGT
  description: sequential breath samples taken for investigation of PEI (reference test)
  arm group label: Dosing arm
  arm group label: Pancreatic cancer (main cohort)
  arm group label: Sub-study cohorts: Chronic pancreatitis, cystic fibrosis, NET patients on SSAs
  other name: 13C MTG breath test
  criteria: 
  gender: All
  minimum age: 16 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Keith Roberts, PhD
  role: Principal Investigator
  affiliation: University Hospital Birmingham NHS Foundation Trust
  last name: Sarah Powell-Brett, MBChB
  phone: 07887754856
  email: sarah.powell-brett1@nhs.net
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: United Kingdom
  responsible party type: Principal Investigator
  investigator affiliation: University Hospital Birmingham NHS Foundation Trust
  investigator full name: Keith John Roberts
  investigator title: Consultant HPB and transplant surgeon
  mesh term: Exocrine Pancreatic Insufficiency