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/NCT05986045</url>
    </required_header>
    <id_info>
      <org_study_id>ENHANCE</org_study_id>
      <nct_id>NCT05986045</nct_id>
    </id_info>
    <brief_title>ENHANCE- Establishing Natural History in an Advanced New CF Care Era</brief_title>
    <official_title>Establishing Natural History in an Advanced New CF Care Era</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Royal College of Surgeons, Ireland</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University Hospital of Limerick</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Cork University Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University College Hospital Galway</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Belfast Health and Social Care Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>NHS Lothian</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Alder Hey Children's NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Manchester University NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Newcastle-upon-Tyne Hospitals NHS Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Cardiff and Vale University Health Board</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Royal Brompton &amp; Harefield NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Erasmus University Rotterdam</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Medizinische Hochschule Brandenburg Theodor Fontane</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Massachusetts General Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>The Hospital for Sick Children</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Teagasc</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Royal College of Surgeons, Ireland</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Measured outcomes for people with CF have improved dramatically over the last 20 years, even&#xD;
        prior to the widespread introduction of cystic fibrosis transmembrane conductance regulator&#xD;
        (CTFR) modulator treatments. The outlook for children with CF has improved significantly,&#xD;
        with longer predicted survival and a lower likelihood of morbidity. This has accelerated&#xD;
        recently. These changes have occurred within a short period of time, and there is much that&#xD;
        we now do not understand about disease progression in children with CF and how this differs&#xD;
        from children without CF. CF is an area which is fortunate to have well-developed and&#xD;
        successful disease registries. CF registries have provided significant amounts of very useful&#xD;
        data to guide improvement in treatment and outcomes over many decades. The power of&#xD;
        registries comes from the collection of a well-defined set of important outcome measures in&#xD;
        very large numbers of people over many years.&#xD;
  &#xD;
        The outcome measures collected routinely in clinical care, which form part of the registries,&#xD;
        are helpful in monitoring moderate-advances and symptomatic disease in people with CF. CF&#xD;
        registries however do not tend to collect tomography(CT) scores, lung clearance index(LCI) or&#xD;
        indeed repeated collection of biomarkers of disease activity such as sweat chloride which are&#xD;
        increasingly relevant in an era of modulator therapies and reducing burden of symptomatic&#xD;
        disease. We perceive an urgent need to complement registry data, cataloguing the changing&#xD;
        natural history if early childhood CF by proactively collecting and curating sensitive,&#xD;
        meaningful outcome data in a large cohort of children during this new era in Ireland and the&#xD;
        UK.&#xD;
  &#xD;
        The prevalence, presentation and natural history of disease manifestation of CF in young&#xD;
        children will change significantly in the next decade with advances in the understanding and&#xD;
        treatment of CF, including the use of therapies aimed at CFTR function. ENHANCE provides an&#xD;
        opportunity to study these changes in real-time and in ways that are relevant to the CF&#xD;
        community.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">September 30, 2028</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2028</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>1. The incidence, prevalence and progression of structural lung disease</measure>
      <time_frame>60 Months</time_frame>
      <description>Spirometry-controlled Computed Tomography</description>
    </primary_outcome>
    <primary_outcome>
      <measure>2. The long-term natural history of pulmonary function and ventilation homogeneity.</measure>
      <time_frame>60 Months</time_frame>
      <description>Spirometry, Multiple Breath Washout</description>
    </primary_outcome>
    <primary_outcome>
      <measure>3. The incidence, prevalence and longitudinal progression of CF liver disease.</measure>
      <time_frame>60 Months</time_frame>
      <description>Liver Ultrasound, Liver Function Tests</description>
    </primary_outcome>
    <primary_outcome>
      <measure>4. The prevalence, natural history and progression of exocrine pancreatic dysfunction</measure>
      <time_frame>60 Months</time_frame>
      <description>Faecal Elastase Analysis</description>
    </primary_outcome>
    <primary_outcome>
      <measure>5. The longitudinal natural history of gastrointestinal symptoms, inflammation and the gut microbiome compared to a healthy control population</measure>
      <time_frame>60 Months</time_frame>
      <description>Microbiome Analysis, Identification of inflammatory markers, Abdominal Symptom Scores</description>
    </primary_outcome>
    <primary_outcome>
      <measure>6. The longitudinal natural history of annual sweat chloride levels in infants and children of different ages, the influence of different treatments on this and its association with other outcomes</measure>
      <time_frame>60 Months</time_frame>
      <description>Sweat chloride</description>
    </primary_outcome>
    <primary_outcome>
      <measure>7. The longitudinal natural history of mental health outcomes in children with CF compared to controls.</measure>
      <time_frame>60 Months</time_frame>
      <description>Mental Health Quality Of Life Questionnaires</description>
    </primary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Anticipated">550</enrollment>
    <condition>Cystic Fibrosis</condition>
    <arm_group>
      <arm_group_label>Cohort 1</arm_group_label>
      <description>Newborn infants diagnosed with Cystic Fibrosis at newborn screening</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort 2</arm_group_label>
      <description>Children with previous diagnosis of Cystic Fibrosis up to 5 years of age</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <description>Newborn infants without cystic fibrosis</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Quality of Life</intervention_name>
      <description>ENHANCE will collect natural history on all children with cystic fibrosis who are enrolled over a 5 year period</description>
      <arm_group_label>Cohort 1</arm_group_label>
      <arm_group_label>Cohort 2</arm_group_label>
      <arm_group_label>Control</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          All participants with CF will be invited to participate in ENHANCE. We will ensure a&#xD;
          presentative mix of mutation groups, sex, ages, ethnicity and location in all cohorts. We&#xD;
          will target recruitment to cohorts 1 and 2 based on the following split of mutations: 50%&#xD;
          F508del homozygous(FF), 20%heterozygous for F508del and a minimum function mutation(FMF),&#xD;
          20% heterozygous for F508del and a residual function/gating mutation or gating/other&#xD;
          mutation and 10% with no currently treatable mutation(NON).&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Children with CF attending one of the study centres and fulling one of the following:&#xD;
  &#xD;
            -  Newborn infant diagnoses with cystic fibrosis through newborn screening (excludes&#xD;
               children with an uncertain diagnosis), or having 2 documented CF disease causing&#xD;
               mutations.&#xD;
  &#xD;
            -  Children with CF (sweat chloride&gt;60mmol/L or 2 CF disease causing mutations) aged 0-6&#xD;
               at study initiation&#xD;
  &#xD;
            -  Healthy control infants without CF&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Children or their parents not willing or able to complete with study procedures or&#xD;
               assessments.&#xD;
  &#xD;
            -  Co-morbidities in groups 1 and 2, unrelated to CF, that in the opinion of the&#xD;
               investigator would substantially impact on study measurements and unduly affect the&#xD;
               veracity of the outcome data, for example a diagnosis of inflammatory bowel disease or&#xD;
               extreme prematurity.&#xD;
  &#xD;
            -  Children in the control group who are carriers of CFTR mutations or have chronic&#xD;
               medical or GI/Liver conditions that in the opinion of the investigator would unduly&#xD;
               affect the veracity of the outcome data.&#xD;
  &#xD;
            -  We will not exclude someone who subsequently joins a CF Investigational drug trial if&#xD;
               they are happy to continue, but if possible, will time their annual ENHANCE data&#xD;
               collection to fall outside the time period of any experimental study drug&#xD;
               administration&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Month</minimum_age>
      <maximum_age>5 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Paul McNally</last_name>
      <role>Principal Investigator</role>
      <affiliation>RCSI</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Karen Lester, PhD</last_name>
      <phone>(01) 4096500</phone>
      <email>karenlester@rcsi.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Rachel Cregan, MSc</last_name>
      <phone>(01) 4096500</phone>
      <email>rachelcregan@rcsi.com</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>August 3, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 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>Cystic Fibrosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05986045
  org study id: ENHANCE
  nct id: NCT05986045
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Measured outcomes for people with CF have improved dramatically over the last 20 years, even
        prior to the widespread introduction of cystic fibrosis transmembrane conductance regulator
        (CTFR) modulator treatments. The outlook for children with CF has improved significantly,
        with longer predicted survival and a lower likelihood of morbidity. This has accelerated
        recently. These changes have occurred within a short period of time, and there is much that
        we now do not understand about disease progression in children with CF and how this differs
        from children without CF. CF is an area which is fortunate to have well-developed and
        successful disease registries. CF registries have provided significant amounts of very useful
        data to guide improvement in treatment and outcomes over many decades. The power of
        registries comes from the collection of a well-defined set of important outcome measures in
        very large numbers of people over many years.
  
        The outcome measures collected routinely in clinical care, which form part of the registries,
        are helpful in monitoring moderate-advances and symptomatic disease in people with CF. CF
        registries however do not tend to collect tomography(CT) scores, lung clearance index(LCI) or
        indeed repeated collection of biomarkers of disease activity such as sweat chloride which are
        increasingly relevant in an era of modulator therapies and reducing burden of symptomatic
        disease. We perceive an urgent need to complement registry data, cataloguing the changing
        natural history if early childhood CF by proactively collecting and curating sensitive,
        meaningful outcome data in a large cohort of children during this new era in Ireland and the
        UK.
  
        The prevalence, presentation and natural history of disease manifestation of CF in young
        children will change significantly in the next decade with advances in the understanding and
        treatment of CF, including the use of therapies aimed at CFTR function. ENHANCE provides an
        opportunity to study these changes in real-time and in ways that are relevant to the CF
        community.
  observational model: Case-Control
  time perspective: Prospective
  measure: 1. The incidence, prevalence and progression of structural lung disease
  time frame: 60 Months
  description: Spirometry-controlled Computed Tomography
  measure: 2. The long-term natural history of pulmonary function and ventilation homogeneity.
  time frame: 60 Months
  description: Spirometry, Multiple Breath Washout
  measure: 3. The incidence, prevalence and longitudinal progression of CF liver disease.
  time frame: 60 Months
  description: Liver Ultrasound, Liver Function Tests
  measure: 4. The prevalence, natural history and progression of exocrine pancreatic dysfunction
  time frame: 60 Months
  description: Faecal Elastase Analysis
  measure: 5. The longitudinal natural history of gastrointestinal symptoms, inflammation and the gut microbiome compared to a healthy control population
  time frame: 60 Months
  description: Microbiome Analysis, Identification of inflammatory markers, Abdominal Symptom Scores
  measure: 6. The longitudinal natural history of annual sweat chloride levels in infants and children of different ages, the influence of different treatments on this and its association with other outcomes
  time frame: 60 Months
  description: Sweat chloride
  measure: 7. The longitudinal natural history of mental health outcomes in children with CF compared to controls.
  time frame: 60 Months
  description: Mental Health Quality Of Life Questionnaires
  arm group label: Cohort 1
  description: Newborn infants diagnosed with Cystic Fibrosis at newborn screening
  arm group label: Cohort 2
  description: Children with previous diagnosis of Cystic Fibrosis up to 5 years of age
  arm group label: Control
  description: Newborn infants without cystic fibrosis
  intervention type: Other
  intervention name: Quality of Life
  description: ENHANCE will collect natural history on all children with cystic fibrosis who are enrolled over a 5 year period
  arm group label: Cohort 1
  arm group label: Cohort 2
  arm group label: Control
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 1 Month
  maximum age: 5 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Paul McNally
  role: Principal Investigator
  affiliation: RCSI
  last name: Karen Lester, PhD
  phone: (01) 4096500
  email: karenlester@rcsi.com
  last name: Rachel Cregan, MSc
  phone: (01) 4096500
  email: rachelcregan@rcsi.com
  responsible party type: Sponsor
  mesh term: Cystic Fibrosis
  sharing ipd: No