Understanding Gut Symptoms in People With Cystic Fibrosis

NCT05934656 | Recruiting

• 1 other identifier: SRC 023
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 1

Brief 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). 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.

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; Stool microbiome; Diet; Phenotypes; Biomarkers; Diet quality; Dietary indices; Bloating; Constipation; Malabsorption; Latent class analysis

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline

Secondary Outcomes (7)

• Association of clusters (primary outcome) with stool inflammatory markers

  through study completion (measured at baseline, 6 and 12 months)

• Association of clusters (primary outcome) with stool elastase

  through study completion (measured at baseline, 6 and 12 months)

• Association of clusters (primary outcome) with stool fat

  through study completion (measured at baseline, 6 and 12 months)

• Association of clusters (primary outcome) with faecal microbiome

  through study completion (measured at baseline, 6 and 12 months)

• Association of clusters (primary outcome) with faecal metabolome

  through study completion (measured at baseline, 6 and 12 months)

Study Arms (1)

People with cystic fibrosis

People with confirmed diagnosis aged over six year old

Other: Latent class analysis

Interventions

Latent class analysis OTHER

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.

People with cystic fibrosis

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Children aged 6-15 years old and adults aged over 16 years old with cystic fibrosis

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• University of Nottingham: lead
• Cystic Fibrosis Trust: collaborator
• Motilent: collaborator
• Nottingham Trent University: collaborator
• Vanderbilt University Medical Center: collaborator
• University of Leeds: collaborator
• Brandenburg Medical School Theodor Fontane: collaborator
• University of Glasgow: collaborator
• National Institute for Health Research, United Kingdom: collaborator
• University of Birmingham: collaborator
• Northumbria University: collaborator
• Imperial College London: collaborator

Study Sites (1)

Nottingham University Hospitals Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

RECRUITING

Related Links

• The Cystic Fibrosis Trust Strategic Research Centres

Biospecimen

Retention: SAMPLES WITHOUT DNA

Stool samples frozen pre-analysis Whole blood samples for the analysis of peripheral blood mononuclear cells (PBMC). PBMCs will be stored at -80oC. Serum samples stored at -80oC.

MeSH Terms

Conditions

Cystic Fibrosis; Inflammation; Constipation; Malabsorption Syndromes

Interventions

Latent Class Analysis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Signs and Symptoms; Intestinal Diseases; Gastrointestinal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cluster Analysis; Statistics as Topic; Epidemiologic Methods; Investigative Techniques; Algorithms; Mathematical Concepts; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Alan Smyth

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Darren J Sills

CONTACT

0115 8230612; darren.sills1@nottingham.ac.uk

GRAMPUS-CF

CONTACT

grampuscf@nottingham.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2023
• First Posted: July 7, 2023
• Study Start: June 26, 2023
• Primary Completion: September 30, 2025
• Study Completion: March 31, 2026
• Last Updated: August 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: 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.
• Access Criteria: 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. Applications 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.

Locations

GB (1)