Ignite Creation Date:
2025-12-24 @ 11:32 PM
Ignite Modification Date:
2025-12-25 @ 9:20 PM
Study NCT ID:
NCT05934656
Status:
RECRUITING
Last Update Posted:
2023-08-07
First Post:
2023-05-30
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Understanding Gut Symptoms in People With Cystic Fibrosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003550', 'term': 'Cystic Fibrosis'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D003248', 'term': 'Constipation'}, {'id': 'D008286', 'term': 'Malabsorption Syndromes'}], 'ancestors': [{'id': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D007232', 'term': 'Infant, Newborn, Diseases'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012817', 'term': 'Signs and Symptoms, Digestive'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077272', 'term': 'Latent Class Analysis'}], 'ancestors': [{'id': 'D016000', 'term': 'Cluster Analysis'}, {'id': 'D013223', 'term': 'Statistics as Topic'}, {'id': 'D004812', 'term': 'Epidemiologic Methods'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D000465', 'term': 'Algorithms'}, {'id': 'D055641', 'term': 'Mathematical Concepts'}, {'id': 'D017531', 'term': 'Health Care Evaluation Mechanisms'}, {'id': 'D011787', 'term': 'Quality of Health Care'}, {'id': 'D017530', 'term': 'Health Care Quality, Access, and Evaluation'}, {'id': 'D011634', 'term': 'Public Health'}, {'id': 'D004778', 'term': 'Environment and Public Health'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'Stool samples frozen pre-analysis\n\nWhole blood samples for the analysis of peripheral blood mononuclear cells (PBMC).\n\nPBMCs will be stored at -80oC.\n\nSerum samples stored at -80oC.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 350}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-06-26', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-08', 'completionDateStruct': {'date': '2026-03-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-08-02', 'studyFirstSubmitDate': '2023-05-30', 'studyFirstSubmitQcDate': '2023-06-28', 'lastUpdatePostDateStruct': {'date': '2023-08-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-07-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-09-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Identification of distinct phenotypes of gastrointestinal symptoms in people with cystic fibrosis', 'timeFrame': 'Baseline', 'description': 'Latent class analysis will be used to determine symptom clusters (phenotypes). This will depend on the scores on the CF-Abd and Patient Assessment of Constipation symptom (PAC-SYM) questionnaires.\n\nCF-Abd includes 28 items rated on a 6-poin. The scoring scale is between 0 and 100 with higher values for increasing frequency and/or severity of symptoms.\n\nPAC-SYM includes 12 items rated on a 5-point (0-4) Likert scale. The global score is the mean of all 12 items. Higher score indicates worse symptoms.\n\nThese, together with the data from the dietary questionnaire (Intake24) will be used in the latent class analysis to determine symptom clusters'}], 'secondaryOutcomes': [{'measure': 'Association of clusters (primary outcome) with stool inflammatory markers', 'timeFrame': 'through study completion (measured at baseline, 6 and 12 months)', 'description': 'Association of clusters (primary outcome) with stool inflammatory markers to explore possible mechanisms: Faecal calprotectin and faecal cytokines'}, {'measure': 'Association of clusters (primary outcome) with stool elastase', 'timeFrame': 'through study completion (measured at baseline, 6 and 12 months)', 'description': 'Association of clusters (primary outcome) with stool elastase (a marker of pancreatic exocrine function) to explore possible mechanisms'}, {'measure': 'Association of clusters (primary outcome) with stool fat', 'timeFrame': 'through study completion (measured at baseline, 6 and 12 months)', 'description': 'Association of clusters (primary outcome) with stool fat to explore possible mechanisms.'}, {'measure': 'Association of clusters (primary outcome) with faecal microbiome', 'timeFrame': 'through study completion (measured at baseline, 6 and 12 months)', 'description': 'Association of clusters (primary outcome) with faecal microbiome to explore possible mechanisms.'}, {'measure': 'Association of clusters (primary outcome) with faecal metabolome', 'timeFrame': 'through study completion (measured at baseline, 6 and 12 months)', 'description': 'Association of clusters (primary outcome) with faecal metabolome to explore possible mechanisms'}, {'measure': 'Association of clusters (primary outcome) with blood markers of gut permeability', 'timeFrame': 'through study completion (measured at baseline, 6 and 12 months)', 'description': 'Association of clusters (primary outcome) with blood markers of gut permeability to explore possible mechanisms.'}, {'measure': 'Association of clusters (primary outcome) with Magnetic Resonance Imaging metrics', 'timeFrame': 'During procedure', 'description': 'Association of clusters (primary outcome) with Magnetic Resonance Imaging metrics to explore possible mechanisms: small bowel water content, orocaecal transit time, colonic volume and motility'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Gastrointestinal symptoms', 'Gastrointestinal transit', 'Gastrointestinal microbiome', 'Inflammation', 'Magnetic Resonance Imaging', 'Oro-caecal transit time', 'Small bowel water', 'Colonic volume', 'Stool microbiome', 'Diet', 'Phenotypes', 'Biomarkers', 'Diet quality', 'Dietary indices', 'Bloating', 'Constipation', 'Malabsorption', 'Latent class analysis'], 'conditions': ['Cystic Fibrosis', 'Gastrointestinal Dysfunction']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'https://www.cysticfibrosis.org.uk/the-work-we-do/research/gut-research-advancing-a-mechanistic-and-personalised-understanding-of', 'label': 'The Cystic Fibrosis Trust Strategic Research Centres'}]}, 'descriptionModule': {'briefSummary': 'Although chest infections affect wellbeing and survival in cystic fibrosis (CF), most people with CF also have difficulty digesting food and must take medication for this. In spite of this treatment, two thirds of people with CF miss school or work because of tummy symptoms (pain, bloating and wind). In some cases these symptoms become severe leading to bowel obstruction and hospital admission. Long term, people with CF have a greater risk of bowel cancer. The investigators asked people with CF and health professionals to suggest the most important questions for research. Treatment of gut symptoms was in their top 10 list. Current treatments are often ineffective because the investigators do not fully understand why symptoms occur. GRAMPUS-CF SRC will describe accurately the categories of gut symptoms in CF and find out why they occur. The investigators will do this using magnetic resonance imaging (MRI) scans and tests which give a detailed description of the germs in the bowel or which measure inflammation. The investigators will also study the effects of diet, using a questionnaire. The investigators will link these results together, using advanced statistics to find the factors causing gut symptoms. The investigators will then identify treatments which are likely to be helpful. In future work the investigators will test these in clinical trials.', 'detailedDescription': "This is a multicentre longitudinal observational study Study.\n\nHypothesis 1 - Distinct phenotypes of gut symptoms in CF can be defined, using symptom questionnaires.\n\nHypothesis 2 - These phenotypes will be characterised by differences in mechanism, elucidated by MRI physiology, gut microbiome, inflammatory markers and dietary factors.\n\nHypothesis 3 - Integration of mechanistic data will identify pathways which can be targeted by new and repurposed therapeutics, dietary modifications and biomarkers to identify those patients likely to benefit.\n\nStudy Design Tiered study (3 groups), using latent class analysis to characterise phenotypes of CF gut symptoms, from clinical and questionnaire data.\n\nNo control group. The investigators will conduct a longitudinal study comprising nested groups A to C of the study population, with progressively more detailed mechanistic investigations.\n\nGroup A will complete a CF-specific measure of gut symptoms (CFAbd-Score) and a generic constipation scoring using the 'Patient Assessment of Constipation-Symptoms' (PAC-SYM) and a dietary questionnaire (Intake24). Participants will provide questionnaire data at 3 time points, 6 months apart (baseline, 6 and 12 months).\n\nGroup B will have stool and blood for microbiome, inflammatory mediators and faecal fat. Participants will provide stool and blood samples at 3 time points, 6 months apart (baseline, 6 and 12 months).\n\nGroup C will have gut MRI and exploratory studies of inflammation (immune gene expression and micro RNA analysis). Participants will spend approximately 6 hours in the MRI scanning suite on a single day.\n\nGroup A - 300 adults \\& 50 children. Group B - 100 adults \\& 20 children (group B participants will be drawn from group A).\n\nGroup C - 40 adults \\& 10 children (group C participants will be drawn from group B).\n\nTotal final enrolment 300 adults \\& 50 children"}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '6 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Children aged 6-15 years old and adults aged over 16 years old with cystic fibrosis', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Confirmed diagnosis of cystic fibrosis (clinical features of CF combined with either a genotype known to be associated with CF or a diagnostic sweat chloride).\n2. For participants enrolled in group A via the mobile phone app, self-reported diagnosis will be accepted.\n3. Adult patients will be aged 16 years and over and attend the Nottingham or Leeds CF Centres.\n4. Paediatric patients will be aged 6-15 years and attend the Nottingham CF Centre.\n5. Capacity to consent, or to understand the requirements of the study where parent or guardian consent is needed.\n6. English-speaking (the panel of questionnaires the investigators will use has so far been validated only in English).\n\nExclusion Criteria:\n\nEXCLUSIONS TO PARTICIPATION IN ANY PART OF THE STUDY\n\n1. Self-reported diagnosis of an additional gastrointestinal condition e.g. inflammatory bowel disease, coeliac disease or gastrointestinal cancer.\n2. Patients from Leeds previously enrolled in the IGLOO-CF Study\\* \\* Data from the IGLOO-CF Study will form the validation dataset for the latent class analysis in GRAMPUS-CF.\n\nEXCLUSIONS TO PARTICIPATION IN GROUP C (MRI SCANS)\n\n1. Measurement of Forced Expiratory Volume in 1 second (FEV1) of \\<40% predicted using Global Lung Initiative criteria, according to clinical records.\n2. Contra-indication to MRI scanning, such as embedded metal, pacemaker.\n3. Unable to stop medications directly prescribed to alter bowel habit, such as laxatives of anti-diarrhoeals, on the study day.\n4. Previous resection of any part of the gastro-intestinal tract apart from appendicectomy or cholecystectomy. Surgical relief of distal intestinal obstruction syndrome or neonatal ileus will be permitted unless clinical records show excision of intestine \\>20cm in length.\n5. Intestinal stoma\n6. Diagnosis of inflammatory bowel disease or coeliac disease confirmed by biopsy\n7. Gastrointestinal malignancy\n8. Unable to comply with dietary restrictions required for the study\n9. Pregnancy - tests are available at the Sir Peter Mansfield Imaging Centre if participants are unsure.'}, 'identificationModule': {'nctId': 'NCT05934656', 'acronym': 'GRAMPUS-CF SRC', 'briefTitle': 'Understanding Gut Symptoms in People With Cystic Fibrosis', 'organization': {'class': 'OTHER', 'fullName': 'University of Nottingham'}, 'officialTitle': 'Gut Research Advancing a Mechanistic and Personalised Understanding of Symptoms in Cystic Fibrosis: The GRAMPUS-CF Strategic Research Centre', 'orgStudyIdInfo': {'id': 'SRC 023'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'People with cystic fibrosis', 'description': 'People with confirmed diagnosis aged over six year old', 'interventionNames': ['Other: Latent class analysis']}], 'interventions': [{'name': 'Latent class analysis', 'type': 'OTHER', 'description': 'The investigators will conduct a longitudinal study comprising nested groups A to C of the study population, with progressively more detailed mechanistic investigations. No control group.\n\nGroup A will complete a CF-specific measure of gut symptoms (CFAbd-Score), a generic constipation score (PAC-SYM) and 24 hour dietary recall (Intake24).\n\nGroup B will have stool and blood for microbiome, inflammatory mediators and faecal fat.\n\nGroup C will have gut MRI and exploratory studies of inflammation.', 'armGroupLabels': ['People with cystic fibrosis']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'NG7 2UH', 'city': 'Nottingham', 'state': 'Nottinghamshire', 'status': 'RECRUITING', 'country': 'United Kingdom', 'contacts': [{'name': 'Darren Sills', 'role': 'CONTACT', 'email': 'darren.sills1@nottingham.ac.uk', 'phone': '07817933762'}], 'facility': 'Nottingham University Hospitals Trust', 'geoPoint': {'lat': 52.9536, 'lon': -1.15047}}], 'centralContacts': [{'name': 'Darren J Sills', 'role': 'CONTACT', 'email': 'darren.sills1@nottingham.ac.uk', 'phone': '0115 8230612'}, {'name': 'GRAMPUS-CF', 'role': 'CONTACT', 'email': 'grampuscf@nottingham.ac.uk'}], 'overallOfficials': [{'name': 'Alan Smyth', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Nottingham'}]}, 'ipdSharingStatementModule': {'timeFrame': 'Applications will be considered from the time that our own data analysis is complete (expected to be 31/12/26), for a maximum of 7 years after study completion.', 'ipdSharing': 'YES', 'description': 'Applications will be considered for access to study data, with no participant identifiers.', 'accessCriteria': "Requests should be addressed to the chief investigator via the study email address (grampuscf@nottingham.ac.uk). Requests will be assessed on a case-by-case basis.\n\nApplications should state the research question being addressed and include a link to the researcher's published protocol. This will be reviewed by the research team and a final decision to share data will be the responsibility of the chief investigator. Data sharing is specifically mentioned in the participant information sheet and consent for this has been obtained."}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Nottingham', 'class': 'OTHER'}, 'collaborators': [{'name': 'Cystic Fibrosis Trust', 'class': 'OTHER'}, {'name': 'Motilent', 'class': 'UNKNOWN'}, {'name': 'Nottingham Trent University', 'class': 'OTHER'}, {'name': 'Vanderbilt University Medical Center', 'class': 'OTHER'}, {'name': 'University of Leeds', 'class': 'OTHER'}, {'name': 'Brandenburg Medical School Theodor Fontane', 'class': 'OTHER'}, {'name': 'University of Glasgow', 'class': 'OTHER'}, {'name': 'National Institute for Health Research, United Kingdom', 'class': 'OTHER_GOV'}, {'name': 'University of Birmingham', 'class': 'OTHER'}, {'name': 'Northumbria University', 'class': 'OTHER'}, {'name': 'Imperial College London', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}