Cystic FibrosisGRAMPUS-CF SRCNCT05934656
Understanding Gut Symptoms in People With Cystic Fibrosis
An observational study of Cystic Fibrosis and Gastrointestinal Dysfunction, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystic Fibrosis, Gastrointestinal Dysfunction
- What is being tested?
- Latent class analysis
- How many people
- 350 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 26 Jun 2023to 31 Mar 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Children aged 6-15 years old and adults aged over 16 years old with cystic fibrosis
Who may be able to join
- 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).
- For participants enrolled in group A via the mobile phone app, self-reported diagnosis will be accepted.
- Adult patients will be aged 16 years and over and attend the Nottingham or Leeds CF Centres.
- Paediatric patients will be aged 6-15 years and attend the Nottingham CF Centre.
- Capacity to consent, or to understand the requirements of the study where parent or guardian consent is needed.
- English-speaking (the panel of questionnaires the investigators will use has so far been validated only in English).
Who cannot join
- EXCLUSIONS TO PARTICIPATION IN ANY PART OF THE STUDY
- Self-reported diagnosis of an additional gastrointestinal condition e.g. inflammatory bowel disease, coeliac disease or gastrointestinal cancer.
- 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.
- EXCLUSIONS TO PARTICIPATION IN GROUP C (MRI SCANS)
- Measurement of Forced Expiratory Volume in 1 second (FEV1) of <40% predicted using Global Lung Initiative criteria, according to clinical records.
- Contra-indication to MRI scanning, such as embedded metal, pacemaker.
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- Unable to stop medications directly prescribed to alter bowel habit, such as laxatives of anti-diarrhoeals, on the study day.
- 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.
- Intestinal stoma
- Diagnosis of inflammatory bowel disease or coeliac disease confirmed by biopsy
- Gastrointestinal malignancy
- Unable to comply with dietary restrictions required for the study
- Pregnancy - tests are available at the Sir Peter Mansfield Imaging Centre if participants are unsure.
Trial locations and contacts
1 site in 1 country.
GRAMPUS-CF contact
United Kingdom1 site, 1 recruiting
- Recruiting
Nottingham University Hospitals Trust
Nottingham, Nottinghamshire, NG7 2UH
Darren Sills, 07817933762, darren.sills1@nottingham.ac.uk
About this study
Official title: Gut Research Advancing a Mechanistic and Personalised Understanding of Symptoms in Cystic Fibrosis: The GRAMPUS-CF Strategic Research Centre
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.
Read the detailed description
This is a multicentre longitudinal observational study Study.
Hypothesis 1 - Distinct phenotypes of gut symptoms in CF can be defined, using symptom questionnaires.
Hypothesis 2 - These phenotypes will be characterised by differences in mechanism, elucidated by MRI physiology, gut microbiome, inflammatory markers and dietary factors.
Hypothesis 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.
Study Design Tiered study (3 groups), using latent class analysis to characterise phenotypes of CF gut symptoms, from clinical and questionnaire data.
No 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.
Group 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).
Group 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).
Group 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.
Group A - 300 adults \& 50 children. Group B - 100 adults \& 20 children (group B participants will be drawn from group A).
Group C - 40 adults \& 10 children (group C participants will be drawn from group B).
Total final enrolment 300 adults \& 50 children
- Conditions
- Cystic Fibrosis, Gastrointestinal Dysfunction
- Being tested
- Latent class analysis
- 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
- Medical subject headings
- Cystic Fibrosis, Inflammation, Constipation, Malabsorption Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Latent class analysisOther
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.
Group A will complete a CF-specific measure of gut symptoms (CFAbd-Score), a generic constipation score (PAC-SYM) and 24 hour dietary recall (Intake24).
Group B will have stool and blood for microbiome, inflammatory mediators and faecal fat.
Group C will have gut MRI and exploratory studies of inflammation.
| Study group | Role | What they receive |
|---|---|---|
| People with cystic fibrosis | People with confirmed diagnosis aged over six year old Receives: Other: Latent class analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of distinct phenotypes of gastrointestinal symptoms in people with cystic fibrosis
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.
CF-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.
PAC-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.
These, together with the data from the dietary questionnaire (Intake24) will be used in the latent class analysis to determine symptom clusters
Measured: Baseline
Secondary outcomes (7)
Association of clusters (primary outcome) with stool inflammatory markers
Association of clusters (primary outcome) with stool inflammatory markers to explore possible mechanisms: Faecal calprotectin and faecal cytokines
Measured: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with stool elastase
Association of clusters (primary outcome) with stool elastase (a marker of pancreatic exocrine function) to explore possible mechanisms
Measured: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with stool fat
Association of clusters (primary outcome) with stool fat to explore possible mechanisms.
Measured: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with faecal microbiome
Association of clusters (primary outcome) with faecal microbiome to explore possible mechanisms.
Measured: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with faecal metabolome
Association of clusters (primary outcome) with faecal metabolome to explore possible mechanisms
Measured: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with blood markers of gut permeability
Association of clusters (primary outcome) with blood markers of gut permeability to explore possible mechanisms.
Measured: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with Magnetic Resonance Imaging metrics
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
Measured: During procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2023
- Study start26 Jun 2023
- Primary completion30 Sep 2025 (estimated)
- Study completion31 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- Cystic Fibrosis Trust, Motilent, Nottingham Trent University, Vanderbilt University Medical Center, University of Leeds, Brandenburg Medical School Theodor Fontane, University of Glasgow, National Institute for Health Research, United Kingdom, University of Birmingham, Northumbria University, Imperial College London
- Responsible party
- Sponsor
- Investigators
- Alan Smyth, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05934656
- Sponsor's protocol ID
- SRC 023
- Acronym
- GRAMPUS-CF SRC
- Status last verified
- Aug 2023
- First submitted
- 30 May 2023
- Last updated
- 7 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Applications will be considered for access to study data, with no participant identifiers.
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut Research Advancing a Mechanistic and Personalised Understanding of Symptoms in Cystic Fibrosis: The GRAMPUS-CF Strategic Research Centre
- ClinicalTrials.gov ID
- NCT05934656
- Acronym / sponsor ID
- GRAMPUS-CF SRC / SRC 023
- Conditions
- Cystic Fibrosis, Gastrointestinal Dysfunction
- Keywords
- Gastrointestinal symptoms, Gastrointestinal transit, Gastrointestinal microbiome, Inflammation, Magnetic Resonance Imaging, Oro-caecal transit time, Small bowel water, Colonic volume
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- Cystic Fibrosis Trust, Motilent, Nottingham Trent University, Vanderbilt University Medical Center, University of Leeds, Brandenburg Medical School Theodor Fontane, University of Glasgow, National Institute for Health Research, United Kingdom, University of Birmingham, Northumbria University, Imperial College London
- Study start
- 26 Jun 2023 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 31 Mar 2026 (estimated)
- First posted
- 7 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicentre longitudinal observational study Study.
Hypothesis 1 - Distinct phenotypes of gut symptoms in CF can be defined, using symptom questionnaires.
Hypothesis 2 - These phenotypes will be characterised by differences in mechanism, elucidated by MRI physiology, gut microbiome, inflammatory markers and dietary factors.
Hypothesis 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.
Study Design Tiered study (3 groups), using latent class analysis to characterise phenotypes of CF gut symptoms, from clinical and questionnaire data.
No 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.
Group 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).
Group 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).
Group 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.
Group A - 300 adults \& 50 children. Group B - 100 adults \& 20 children (group B participants will be drawn from group A).
Group C - 40 adults \& 10 children (group C participants will be drawn from group B).
Total final enrolment 300 adults \& 50 children
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| People with cystic fibrosis | – | Other: Latent class analysisPeople with confirmed diagnosis aged over six year old |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children aged 6-15 years old and adults aged over 16 years old with cystic fibrosis
Key inclusion criteria (6 listed)
- 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).
- For participants enrolled in group A via the mobile phone app, self-reported diagnosis will be accepted.
- Adult patients will be aged 16 years and over and attend the Nottingham or Leeds CF Centres.
- Paediatric patients will be aged 6-15 years and attend the Nottingham CF Centre.
- Capacity to consent, or to understand the requirements of the study where parent or guardian consent is needed.
Key exclusion criteria (13 listed)
- EXCLUSIONS TO PARTICIPATION IN ANY PART OF THE STUDY
- Self-reported diagnosis of an additional gastrointestinal condition e.g. inflammatory bowel disease, coeliac disease or gastrointestinal cancer.
- 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.
- EXCLUSIONS TO PARTICIPATION IN GROUP C (MRI SCANS)
- Measurement of Forced Expiratory Volume in 1 second (FEV1) of <40% predicted using Global Lung Initiative criteria, according to clinical records.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Latent class analysisThe 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. Group A will complete a CF-specific measure of gut symptoms (CFAbd-Score), a generic constipation score (PAC-SYM) and 24 hour dietary recall (Intake24). Group B will have stool and blood for microbiome, inflammatory mediators and faecal fat. Group C will have gut MRI and exploratory studies of inflammation. | Other | People with cystic fibrosis |
Primary outcome
Identification of distinct phenotypes of gastrointestinal symptoms in people with cystic fibrosis
Time frame: Baseline
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. CF-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. PAC-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. These, together with the data from the dietary questionnaire (Intake24) will be used in the latent class analysis to determine symptom clusters
7 secondary outcomes
Association of clusters (primary outcome) with stool inflammatory markers
Time frame: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with stool elastase
Time frame: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with stool fat
Time frame: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with faecal microbiome
Time frame: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with faecal metabolome
Time frame: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with blood markers of gut permeability
Time frame: through study completion (measured at baseline, 6 and 12 months)
Association of clusters (primary outcome) with Magnetic Resonance Imaging metrics
Time frame: During procedure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2023.
- The Cystic Fibrosis Trust Strategic Research CentresLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Applications will be considered for access to study data, with no participant identifiers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GRAMPUS-CF contact
Alan Smyth principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis and Gastrointestinal Dysfunction, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Darren J Sills (0115 8230612, darren.sills1@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of distinct phenotypes of gastrointestinal symptoms in people with cystic fibrosis (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2023.