Gut Research Advancing a Mechanistic and Personalised Understanding of Symptoms in Cystic Fibrosis: The GRAMPUS-CF Strategic Research Centre
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- Identification of distinct phenotypes of gastrointestinal symptoms in people with cystic fibrosis
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
- •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.
结局指标
主要结局
Identification of distinct phenotypes of gastrointestinal symptoms in people with cystic fibrosis
时间窗: 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
次要结局
- 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 metabolome(through study completion (measured at baseline, 6 and 12 months))
- Association of clusters (primary outcome) with blood markers of gut permeability(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 Magnetic Resonance Imaging metrics(During procedure)