MRI Parameters as Biomarkers in Cystic Fibrosis (FEMPTO)

A Feasibility Study Evaluating MRI Parameters as Biomarkers of the Effect of a Secretagogue in Cystic Fibrosis (FEMPTO)

Cystic fibrosis (CF) is an inherited condition that affects several organs, including the gut. People with CF often experience uncomfortable digestive symptoms such as bloating, gas, abdominal pain, and constipation. The root cause is that the gut produces thicker-than-normal mucus, which slows things down and makes it harder for the bowel to work properly.

Current treatments such as laxatives, enemas, or surgery can be inconvenient and don't always work well. There is a real need for better options, and for a clearer understanding of how the CF gut behaves and responds to treatment.

This study will use MRI, a non-invasive imaging technique, to look at how fluid moves through the gut in adults with CF and the impact of linaclotide. Linaclotide is a licensed medication used to treat chronic constipation and irritable bowel syndrome. It works by encouraging the gut to release more fluid, helping things move more easily. It acts locally in the gut and is not absorbed into the bloodstream. Early research suggests it may help in CF in a way that does not rely on correcting the underlying genetic fault, making it a promising avenue to explore.

Participants will include people with different bowel habits, including those who tend towards constipation and those who tend towards diarrhoea. The scans will help researchers check whether certain MRI measurements can reliably detect changes in gut fluid and movement.

This is a feasibility study; its main objective is to test whether these MRI measurements are useful and practical, and support a sample size calculation, in future CF studies investigating linaclotide effects.

Inclusion Criteria:

• • Participant is willing and able to give informed consent for participation in the study.

  • Proven diagnosis of CF.
  • Aged between 18-60 years.
  • Ability to conform to the study protocol, including overnight fasting, dietary and lifestyle restriction, administering linaclotide and placebo intervention, MRI scanning, consuming the two study meals and blue muffins, and rating stool frequency and appearance.

Exclusion Criteria:

• Pregnant (current or planned during the study duration) or breastfeeding
• Currently taking regular medicines (i.e., pain relief medication like ibuprofen/paracetamol) apart from cystic fibrosis medicines (i.e., pancreatic enzyme replacement therapy (PERT) medication, CFTR modulators). There are some other medicines it is OK to take such as:
• Some antidepressants (SSRIs or low-dose tricyclics)
• Antihistamines (for allergies)
• The contraceptive pill
• Any resections (surgery) of the intestines, not including removal of the appendix
• Serious medical conditions including any other digestive disorder unrelated to CF.
• Taken a course of intravenous or oral antibiotics in the last 2 weeks (except prophylactic antibiotics such as azithromycin).
• Inability to stop opiates
• Inability to have MRI scans (this could be due to some metallic implants, pacemaker, history of metallic foreign body in your eye and penetrating eye injury)
• Night shift work during the week before study days
• BMI under 18.5 or above 35 kg/m2.
• Taken part in a CTIMP study in the last 4 weeks involving invasive procedures.
• currently has chronic diarrhoea symptoms.