<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/NCT03282903</url>
  </required_header>
  <id_info>
    <org_study_id>16/WM/0152</org_study_id>
    <secondary_id>IRAS183889</secondary_id>
    <nct_id>NCT03282903</nct_id>
  </id_info>
  <brief_title>The PRognostic Effect of Environmental Factors in Crohn's and Colitis</brief_title>
  <acronym>PREdiCCt</acronym>
  <official_title>The PRognostic Effect of Environmental Factors in Crohn's and Colitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Edinburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Aberdeen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Wellcome Trust Sanger Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>NHS Lothian</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chief Scientist Office of the Scottish Government</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Crohn's and Colitis in Childhood</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cure Crohn's and Colitis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Edinburgh and Lothain Health Fund (Lothian Health Board)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Edinburgh</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>
      The PREdiCCt Study:&#xD;
&#xD;
      This is a major study that is now being launched. This is the first study of its kind and is&#xD;
      specifically directed toward understanding how environmental factors and the gut&#xD;
      microorganisms influence IBD flare and recovery. For the PREdiCCt study, the investigators&#xD;
      hope to recruit 3100 people in remission from Crohn's disease or ulcerative colitis (illness&#xD;
      under control) from 28 inflammatory bowel disease clinics across the UK.&#xD;
&#xD;
      The investigators hope to conduct the study in the following stages;-&#xD;
&#xD;
        1. Patients with Crohn's disease, ulcerative colitis or inflammatory bowel disease&#xD;
           unclassified (IBDU) in clinical remission (under control) will be approached in&#xD;
           gastroenterology clinics across the country and invited to take part in the PREdiCCt&#xD;
           study. Alternatively they will express their interest in the study after seeing PREdiCCt&#xD;
           promotional leaflets/posters/videos/social media.&#xD;
&#xD;
        2. Participants will attend a clinic visit for routine tests and also to complete several&#xD;
           questionnaires with a research nurse.&#xD;
&#xD;
        3. At home over the next week participants will complete detailed questionnaires assessing&#xD;
           their environment and diet. Participants will also collect a stool and saliva sample and&#xD;
           send this to our laboratories (the investigators have developed easy ways of doing this&#xD;
           reliably by post). The stool sample is to analyse the microorganisms in the&#xD;
           participant's gut and the saliva is used to analyse their DNA. In addition to this the&#xD;
           participants are asked to complete a 4-day weighed food diary. The food diary is sent to&#xD;
           the University of Aberdeen for analysis.&#xD;
&#xD;
        4. Investigators will then follow patients' progress over 24 months. They will be asked to&#xD;
           complete a short questionnaire every month with a longer questionnaire after 12 months&#xD;
           and culminating in a final questionnaire 24 months after their initial clinic visit.&#xD;
&#xD;
        5. If a participant experiences a flare, investigators will collect an additional stool&#xD;
           sample; but most importantly investigators will look to see how the environmental and&#xD;
           microorganism factors recorded at the beginning differ for those that flare up versus&#xD;
           those that don't.&#xD;
&#xD;
      What investigators hope to achieve;-&#xD;
&#xD;
        1. Finding out the environmental and dietary factors for patients to avoid because they&#xD;
           trigger flare.&#xD;
&#xD;
        2. Finding out behaviours for patients to adopt because they bring about remission.&#xD;
&#xD;
        3. Finding out what the microorganisms that predict flare look like.&#xD;
&#xD;
        4. Gaining information which helps future studies aimed at finding better diets for IBD&#xD;
           sufferers.&#xD;
&#xD;
        5. Developing ways of gathering information online from IBD patients about their well-being&#xD;
           that doctors can routinely use.&#xD;
&#xD;
      The investigators have assembled expert doctors, epidemiologists, microbiologists, nutrition&#xD;
      scientists, and bioinformaticians. These experts will use the systems the investigators have&#xD;
      put in place to make sure PREdiCCt succeeds. It will yield a lot of new information to help&#xD;
      sufferers right away; but the information will also help to kick start many important future&#xD;
      studies that will bring us ever closer to a cure for Crohn's disease and ulcerative colitis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      Inflammatory bowel disease (IBD) is a common cause of chronic ill-health among young people&#xD;
      in the UK (prevalence estimated at 1 in 200 for adults and 1 in 2000 for children, with a&#xD;
      peak incidence in the second and third decades of life)1-2. The major forms of IBD, namely&#xD;
      Crohn's disease (CD) and ulcerative colitis (UC), all too often confer a lifetime of&#xD;
      unpleasant, intrusive and potentially dangerous burden of intestinal inflammation on&#xD;
      individuals. Typical symptoms include abdominal pain, diarrhoea, weight loss, and lethargy.&#xD;
      These adversely affect schooling, work attainment, psycho-social well-being and sexual health&#xD;
      3-4. IBD costs the NHS £720 million per year, based on an average per patient cost of £3,000;&#xD;
      of which half of the costs are directly attributable to relapsing patients 5. Healthcare&#xD;
      expenditure focus in IBD is shifting from hospitalisation and surgery to medical therapy 6.&#xD;
      However, existing treatment modalities remain limited by lack of efficacy, unacceptable&#xD;
      toxicity and poor patient acceptability. Major surgical intervention is frequently required&#xD;
      (&gt;50% in CD; ~20% in UC), with a high risk of disease recurrence, and there is an increased&#xD;
      risk of cancer (in CD), with the highest incidence of colon cancer observed in those patients&#xD;
      with poorly controlled disease 7. Nevertheless, there is a wide spectrum of disease severity.&#xD;
      Around one third of patients will follow a relatively quiescent disease course 8.&#xD;
      Understanding who gets severe, progressive disease and why, is an urgent research priority.&#xD;
      Accurate prediction of these patients will enable precise, tailored intervention early in the&#xD;
      disease course. This should reduce the substantial morbidity and costs associated with IBD.&#xD;
&#xD;
      Genetics, Environment and the Microbiota and Disease Natural History.&#xD;
&#xD;
      Genetic factors play a modest role in defining disease location and extent but not disease&#xD;
      behaviour 9-12. There is very limited evidence about the gut microbiota in disease&#xD;
      progression, although emerging data support a potential role in treatment response. We cannot&#xD;
      alter our genes and, despite intense interest in modifying the gut microbiota (e.g. faecal&#xD;
      transplantation) there is only limited clinically data to support this 13-14. However, it is&#xD;
      within our control to change what we eat and to therefore potentially modify our gut&#xD;
      microbiota to a more favourable phenotype. Patients suspect this should be part of the&#xD;
      answer: one of the commonest questions in the clinic is, &quot;What should I eat?&quot; Established&#xD;
      clinical strategies include the use of exclusive enteral nutrition (EEN) to induce remission&#xD;
      in CD, and a low fibre diet to alleviate obstructive symptoms in stricturing disease 15.&#xD;
      However, beyond this there is presently very limited data to support any on-going specific&#xD;
      dietary strategy for the vast majority of patients with IBD 16. Multiple lines of emerging&#xD;
      evidence in animal models suggest that diets high in natural plant fibres favour an&#xD;
      anti-inflammatory gut milieu, via alterations in the gut microbiota, measurable by&#xD;
      short-chain fatty acid (SCFA) concentrations in stool 17. Dietary fibre may protect against&#xD;
      the development of IBD, through several mechanisms, through its conversion to acetate,&#xD;
      butyrate and propionate (the major SCFAs). Firstly, butyrate is the main energy source for&#xD;
      colonocytes and is associated with the maintenance of the intestinal epithelium 18. Secondly,&#xD;
      SCFAs have immunomodulatory roles including inhibition of the transcription factor NF-KB and&#xD;
      are the only known ligands of G-protein-coupled receptor, GPR43, which limits the&#xD;
      inflammatory response 19-20. Interestingly, the fermentation of fibre is dependent on gut&#xD;
      microbiota, such as Bacteroidetes species, which are deficient in patients with IBD 21. The&#xD;
      individual source of fibre may also be important. In the US Nurses' Health Study of 170,776&#xD;
      women with 3,317,425 person-years of follow-up over 26 years there were 269 incident cases of&#xD;
      Crohn's disease diagnosed and 338 cases of ulcerative colitis 22. For the latter illness,&#xD;
      there were no associations with either total dietary fibre intake or fibre from any specific&#xD;
      food groups. However, for Crohn's disease the highest quintile of energy-adjusted cumulative&#xD;
      average dietary fibre intake, namely 24.3 g/day, was associated with a 41% reduction in risk&#xD;
      compared with the lowest quintile (hazard ratio (HR) =0.59, 95% confidence interval&#xD;
      (CI=)=0.39-0.90). This reduction was associated with the fibre content from fruits (highest&#xD;
      vs. lowest quintile HR=0.57, 95% CI=0.38-0.85) with no associations detected between fibre&#xD;
      from vegetables, cereals or legumes.&#xD;
&#xD;
      These are important issues; the lack of data means patients may resort to untested and&#xD;
      potentially harmful 'fad' diets 16. More pressingly, this is potentially a novel therapeutic&#xD;
      approach to both induce and maintain prolonged remission. Interventional studies in cases and&#xD;
      controls will be necessary, but first further data are required from observational&#xD;
      epidemiological studies to inform which 'interventions' are indicated and/or justified.&#xD;
&#xD;
      Rationale for the Study&#xD;
&#xD;
      It is presently very hard to predict which IBD patients in remission will flare and when.&#xD;
      Scant data are available to advise patients on any substantial lifestyle measure they can&#xD;
      adopt to help prevent or retard future disease from flaring. Potential areas of direct&#xD;
      relevance to patients are aspects of habitual diet, regular exercise, sleep and stress,&#xD;
      including that from major life events. It is hypothesised that there are multiple factors in&#xD;
      habitual diet that are associated with increased risk of disease flare, including reduced&#xD;
      levels of dietary fibre, high levels of n-6 PUFAs, low levels of n-3 PUFAs and dietary&#xD;
      emulsifiers. High levels of regular physical activity are also hypothesised to reduce the&#xD;
      rates of disease flare. These dietary aspects and facets in concert with other lifestyle&#xD;
      factors may contribute in part to the intestinal dysbiosis associated with flare, where the&#xD;
      investigators anticipate seeing a reduction in microbial diversity.&#xD;
&#xD;
      The major aim of this study is to identify the environmental and gut microbiota factors that&#xD;
      predispose to disease flare and influence disease outcomes in IBD. Further, the investigators&#xD;
      aim to build intelligent predictive models of disease behaviour and prognosis combining&#xD;
      phenotypic, environmental and biological data inputs of direct clinical utility.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 1, 2016</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">March 16, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical flare</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Patients will be asked to answer a monthly follow up, providing details of their IBD over the last month. A clinical flare will be determined by a patient answering &quot;no&quot; to the following question in the monthly follow up:&#xD;
&quot;Do you think your disease has been well controlled in the past 1 month?&quot;</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hard clinical flare</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Clinical flare (primary outcome) plus commencement of any new medication; altered dosing of existing medication for the treatment of IBD flare, with an increase in CRP (&gt;5mg/L) and / or faecal calprotectin (&gt;200mcg/g).</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">3100</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <condition>Crohn Disease</condition>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Crohn's disease patients</arm_group_label>
    <description>1550 Crohn's disease patients who are symptomatically controlled.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ulcerative Colitis patients</arm_group_label>
    <description>1550 Ulcerative Colitis patients who are symptomatically controlled.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Stool sample (for microbiome analysis) Saliva sample (for genomic analysis) Blood sample (for&#xD;
      biochemical, haematological and genomic analysis)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        IBD patients with a confirmed diagnosis of Crohn's Disease, Ulcerative Colitis or IBD&#xD;
        unspecified, who are in clinical remission, &gt;6 since diagnosis, &gt;2 months since any change&#xD;
        in therapy for Crohn's disease, ulcerative colitis or IBDU, aged 6 or over at study entry&#xD;
        and who informed consent can be obtained from (or parent/guardian).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Confirmed Crohn's disease or ulcerative colitis or IBDU (Lennard-Jones/Porto criteria).&#xD;
&#xD;
        Clinical remission (see definition Section 3.2 of protocol) &gt;6 months since diagnosis with&#xD;
        Crohn's disease, ulcerative colitis or IBDU &gt;2 months since any change in therapy for&#xD;
        Crohn's disease, ulcerative colitis or IBDU Aged six years or over at study entry Written&#xD;
        informed consent obtained from patient or parent / guardian&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Patient unwilling to take part in all aspects of the study Unable to obtain written&#xD;
        informed consent Systemic corticosteroids (oral or intravenous) within the last two months&#xD;
        Thiopurines / methotrexate / biologic therapy started in the preceding two months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Charlie Lees</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Edinburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aberdeen Royal Infirmary</name>
      <address>
        <city>Aberdeen</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bronglais General Hospital</name>
      <address>
        <city>Aberystwyth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Lanarkshire</name>
      <address>
        <city>Airdrie</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ulster Hospital</name>
      <address>
        <city>Belfast</city>
        <zip>BT16 1RH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bristol Royal Infirmary</name>
      <address>
        <city>Bristol</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Suffolk NHS Foundation Trust</name>
      <address>
        <city>Bury Saint Edmunds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge Addenbrooke's Hospital</name>
      <address>
        <city>Cambridge</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glangwili General Hospital</name>
      <address>
        <city>Carmarthen</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Coventry &amp; Warwickshire</name>
      <address>
        <city>Coventry</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Darlington Memorial Hospital</name>
      <address>
        <city>Darlington</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ninewells Hospital</name>
      <address>
        <city>Dundee</city>
        <zip>DD2 1UB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastbourne General Hospital</name>
      <address>
        <city>Eastbourne</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western General Hospital</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH4 2XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hospital for Sick Children,Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH9 1LF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Devon and Exeter Hospital</name>
      <address>
        <city>Exeter</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Gateshead</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glasgow Royal Infirmary</name>
      <address>
        <city>Glasgow</city>
        <zip>G4 0SF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth University Hospital</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hospital for Children, Glasgow</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Withybush General Hospital</name>
      <address>
        <city>Haverfordwest</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Raigmore Hospital</name>
      <address>
        <city>Inverness</city>
        <zip>IV2 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kettering General Hospital NHS Foundation Trust</name>
      <address>
        <city>Kettering</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth King's Lynn</name>
      <address>
        <city>King's Lynn</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kingston Hospital</name>
      <address>
        <city>Kingston Upon Thames</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Fife</name>
      <address>
        <city>Kirkcaldy</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Forth Valley</name>
      <address>
        <city>Larbert</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Liverpool and Broadgreen University Hospitals NHS Trust</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John's Hospital</name>
      <address>
        <city>Livingston</city>
        <zip>EH54 6PP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's and St Thomas' NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Free Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal London Hospital (Barts Health)</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newcastle Royal Victoria Hospital</name>
      <address>
        <city>Newcastle</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust</name>
      <address>
        <city>Nottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Berkshire Hospital</name>
      <address>
        <city>Reading</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salford Royal Hospital</name>
      <address>
        <city>Salford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandwell and West Birmingham Hospitals NHS Trust</name>
      <address>
        <city>Sandwell</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Buckinghamshire Healthcare NHS Trust</name>
      <address>
        <city>Stoke Mandeville</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Musgrove Park Hospital</name>
      <address>
        <city>Taunton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pinderfield General Hospital</name>
      <address>
        <city>Wakefield</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Warrington and Halton NHS FT</name>
      <address>
        <city>Warrington</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hampshire Hospital</name>
      <address>
        <city>Winchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>October 5, 2021</last_update_submitted>
  <last_update_submitted_qc>October 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2021</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>Crohn Disease</mesh_term>
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Anonymised data will be shared with collaborators to allow analysis.&#xD;
Only aggregate level data will be published.</ipd_description>
  </patient_data>
  <!-- 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/NCT03282903
org study id: 16/WM/0152
secondary id: IRAS183889
nct id: NCT03282903
lead sponsor: 
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has dmc: No
is fda regulated drug: No
is fda regulated device: No
The PREdiCCt Study:

      This is a major study that is now being launched. This is the first study of its kind and is
      specifically directed toward understanding how environmental factors and the gut
      microorganisms influence IBD flare and recovery. For the PREdiCCt study, the investigators
      hope to recruit 3100 people in remission from Crohn's disease or ulcerative colitis (illness
      under control) from 28 inflammatory bowel disease clinics across the UK.

      The investigators hope to conduct the study in the following stages;-

        1. Patients with Crohn's disease, ulcerative colitis or inflammatory bowel disease
           unclassified (IBDU) in clinical remission (under control) will be approached in
           gastroenterology clinics across the country and invited to take part in the PREdiCCt
           study. Alternatively they will express their interest in the study after seeing PREdiCCt
           promotional leaflets/posters/videos/social media.

        2. Participants will attend a clinic visit for routine tests and also to complete several
           questionnaires with a research nurse.

        3. At home over the next week participants will complete detailed questionnaires assessing
           their environment and diet. Participants will also collect a stool and saliva sample and
           send this to our laboratories (the investigators have developed easy ways of doing this
           reliably by post). The stool sample is to analyse the microorganisms in the
           participant's gut and the saliva is used to analyse their DNA. In addition to this the
           participants are asked to complete a 4-day weighed food diary. The food diary is sent to
           the University of Aberdeen for analysis.

        4. Investigators will then follow patients' progress over 24 months. They will be asked to
           complete a short questionnaire every month with a longer questionnaire after 12 months
           and culminating in a final questionnaire 24 months after their initial clinic visit.

        5. If a participant experiences a flare, investigators will collect an additional stool
           sample; but most importantly investigators will look to see how the environmental and
           microorganism factors recorded at the beginning differ for those that flare up versus
           those that don't.

      What investigators hope to achieve;-

        1. Finding out the environmental and dietary factors for patients to avoid because they
           trigger flare.

        2. Finding out behaviours for patients to adopt because they bring about remission.

        3. Finding out what the microorganisms that predict flare look like.

        4. Gaining information which helps future studies aimed at finding better diets for IBD
           sufferers.

        5. Developing ways of gathering information online from IBD patients about their well-being
           that doctors can routinely use.

      The investigators have assembled expert doctors, epidemiologists, microbiologists, nutrition
      scientists, and bioinformaticians. These experts will use the systems the investigators have
      put in place to make sure PREdiCCt succeeds. It will yield a lot of new information to help
      sufferers right away; but the information will also help to kick start many important future
      studies that will bring us ever closer to a cure for Crohn's disease and ulcerative colitis.
Background

      Inflammatory bowel disease (IBD) is a common cause of chronic ill-health among young people
      in the UK (prevalence estimated at 1 in 200 for adults and 1 in 2000 for children, with a
      peak incidence in the second and third decades of life)1-2. The major forms of IBD, namely
      Crohn's disease (CD) and ulcerative colitis (UC), all too often confer a lifetime of
      unpleasant, intrusive and potentially dangerous burden of intestinal inflammation on
      individuals. Typical symptoms include abdominal pain, diarrhoea, weight loss, and lethargy.
      These adversely affect schooling, work attainment, psycho-social well-being and sexual health
      3-4. IBD costs the NHS £720 million per year, based on an average per patient cost of £3,000;
      of which half of the costs are directly attributable to relapsing patients 5. Healthcare
      expenditure focus in IBD is shifting from hospitalisation and surgery to medical therapy 6.
      However, existing treatment modalities remain limited by lack of efficacy, unacceptable
      toxicity and poor patient acceptability. Major surgical intervention is frequently required
      (>50% in CD; ~20% in UC), with a high risk of disease recurrence, and there is an increased
      risk of cancer (in CD), with the highest incidence of colon cancer observed in those patients
      with poorly controlled disease 7. Nevertheless, there is a wide spectrum of disease severity.
      Around one third of patients will follow a relatively quiescent disease course 8.
      Understanding who gets severe, progressive disease and why, is an urgent research priority.
      Accurate prediction of these patients will enable precise, tailored intervention early in the
      disease course. This should reduce the substantial morbidity and costs associated with IBD.

      Genetics, Environment and the Microbiota and Disease Natural History.

      Genetic factors play a modest role in defining disease location and extent but not disease
      behaviour 9-12. There is very limited evidence about the gut microbiota in disease
      progression, although emerging data support a potential role in treatment response. We cannot
      alter our genes and, despite intense interest in modifying the gut microbiota (e.g. faecal
      transplantation) there is only limited clinically data to support this 13-14. However, it is
      within our control to change what we eat and to therefore potentially modify our gut
      microbiota to a more favourable phenotype. Patients suspect this should be part of the
      answer: one of the commonest questions in the clinic is, "What should I eat?" Established
      clinical strategies include the use of exclusive enteral nutrition (EEN) to induce remission
      in CD, and a low fibre diet to alleviate obstructive symptoms in stricturing disease 15.
      However, beyond this there is presently very limited data to support any on-going specific
      dietary strategy for the vast majority of patients with IBD 16. Multiple lines of emerging
      evidence in animal models suggest that diets high in natural plant fibres favour an
      anti-inflammatory gut milieu, via alterations in the gut microbiota, measurable by
      short-chain fatty acid (SCFA) concentrations in stool 17. Dietary fibre may protect against
      the development of IBD, through several mechanisms, through its conversion to acetate,
      butyrate and propionate (the major SCFAs). Firstly, butyrate is the main energy source for
      colonocytes and is associated with the maintenance of the intestinal epithelium 18. Secondly,
      SCFAs have immunomodulatory roles including inhibition of the transcription factor NF-KB and
      are the only known ligands of G-protein-coupled receptor, GPR43, which limits the
      inflammatory response 19-20. Interestingly, the fermentation of fibre is dependent on gut
      microbiota, such as Bacteroidetes species, which are deficient in patients with IBD 21. The
      individual source of fibre may also be important. In the US Nurses' Health Study of 170,776
      women with 3,317,425 person-years of follow-up over 26 years there were 269 incident cases of
      Crohn's disease diagnosed and 338 cases of ulcerative colitis 22. For the latter illness,
      there were no associations with either total dietary fibre intake or fibre from any specific
      food groups. However, for Crohn's disease the highest quintile of energy-adjusted cumulative
      average dietary fibre intake, namely 24.3 g/day, was associated with a 41% reduction in risk
      compared with the lowest quintile (hazard ratio (HR) =0.59, 95% confidence interval
      (CI=)=0.39-0.90). This reduction was associated with the fibre content from fruits (highest
      vs. lowest quintile HR=0.57, 95% CI=0.38-0.85) with no associations detected between fibre
      from vegetables, cereals or legumes.

      These are important issues; the lack of data means patients may resort to untested and
      potentially harmful 'fad' diets 16. More pressingly, this is potentially a novel therapeutic
      approach to both induce and maintain prolonged remission. Interventional studies in cases and
      controls will be necessary, but first further data are required from observational
      epidemiological studies to inform which 'interventions' are indicated and/or justified.

      Rationale for the Study

      It is presently very hard to predict which IBD patients in remission will flare and when.
      Scant data are available to advise patients on any substantial lifestyle measure they can
      adopt to help prevent or retard future disease from flaring. Potential areas of direct
      relevance to patients are aspects of habitual diet, regular exercise, sleep and stress,
      including that from major life events. It is hypothesised that there are multiple factors in
      habitual diet that are associated with increased risk of disease flare, including reduced
      levels of dietary fibre, high levels of n-6 PUFAs, low levels of n-3 PUFAs and dietary
      emulsifiers. High levels of regular physical activity are also hypothesised to reduce the
      rates of disease flare. These dietary aspects and facets in concert with other lifestyle
      factors may contribute in part to the intestinal dysbiosis associated with flare, where the
      investigators anticipate seeing a reduction in microbial diversity.

      The major aim of this study is to identify the environmental and gut microbiota factors that
      predispose to disease flare and influence disease outcomes in IBD. Further, the investigators
      aim to build intelligent predictive models of disease behaviour and prognosis combining
      phenotypic, environmental and biological data inputs of direct clinical utility.
observational model: Cohort
time perspective: Prospective
measure: Clinical flare
time frame: Up to 2 years
description: Patients will be asked to answer a monthly follow up, providing details of their IBD over the last month. A clinical flare will be determined by a patient answering "no" to the following question in the monthly follow up:
"Do you think your disease has been well controlled in the past 1 month?"
measure: Hard clinical flare
time frame: Up to 2 years
description: Clinical flare (primary outcome) plus commencement of any new medication; altered dosing of existing medication for the treatment of IBD flare, with an increase in CRP (>5mg/L) and / or faecal calprotectin (>200mcg/g).
arm group label: Crohn's disease patients
description: 1550 Crohn's disease patients who are symptomatically controlled.
arm group label: Ulcerative Colitis patients
description: 1550 Ulcerative Colitis patients who are symptomatically controlled.
Stool sample (for microbiome analysis) Saliva sample (for genomic analysis) Blood sample (for
      biochemical, haematological and genomic analysis)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: No
last name: Charlie Lees
role: Principal Investigator
affiliation: University of Edinburgh
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country: United Kingdom
responsible party type: Sponsor
mesh term: Crohn Disease
mesh term: Colitis
mesh term: Inflammatory Bowel Diseases
sharing ipd: No
ipd description: Anonymised data will be shared with collaborators to allow analysis.
Only aggregate level data will be published.