MRI Parameters as Biomarkers in Cystic Fibrosis (FEMPTO) (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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cystic Fibrosis (CF)
• Intervention / Treatment: Drug: Placebo; Drug: Linaclotide 290 micrograms

Detailed Description

Background: The recent James Lind Alliance priority setting listed "How can we relieve gastro-intestinal symptoms, such as stomach pain, bloating and nausea?" as number 3 priority despite treatment with CFTR modulators. The investigators have shown using magnetic resonance imaging (MRI) that pwCF have abnormal small bowel contents which empty more slowly into the colon. This is most likely due to impaired pancreatic, biliary and intestinal secretions leading to hyperviscosity of contents. Linaclotide is a drug which stimulates bicarbonate secretion in the small intestine which has been shown to accelerate transit in mice models of CF but not in patients. Its action would be predicted to reduce mucus viscosity and normalise small bowel contents and transit.

Aims: to perform a mechanistic pilot study using MRI to show that linaclotide normalises small bowel contents and transit times.

Methods: A randomised, placebo-controlled trial of linaclotide in pwCF. Linaclotide 290ug will be taken on the day before and on the MRI study day. Patients will then undergo serial MRI scanning for 6 hours following dosing at time T 0 , with a standard rice pudding meal at time T60 and a second 700kcal meal at T 300 minutes with the final scan at time T360minutes as the investigators have done previously. The investigators will measure small bowel water content (SBWC) as well as time for chyme to enter the colon (orocaecal transit time [OCTT]) and T1 ascending colon(T1AC), a measure of colonic water content. Primary endpoint: SBWC AUC 0-6hours . Secondary endpoints: change in SBWC after second meal from T300 to T360 ( ∆ SBWC), OCTT, T1 AC AUC 0-6 hours, bowel frequency and stool consistency on study day and the following 3 days.

Impact: If successful this will provide a mechanistic rationale for a full 12 week clinical study of linaclotide as adjunctive treatment for pwCF.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Abi Spicer, PhD; Phone Number: +44-7855 193162; Email: MS-fempto@nottingham.ac.uk

Study Locations

• United Kingdom
  • Gloucestershire
    • Nottingham, Gloucestershire, United Kingdom, NG7 2UH
      • Sir Peter Mansfield Imaging Centre
      • Contact: Abi Spicer, PhD; Phone Number: +447855 193162; Email: MS-fempto@nottingham.ac.uk
      • Contact: Robin Spiller, MD; Phone Number: +44-7824328319; Email: robin.spiller@nottingham.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; encapsulated lactose	Drug: Placebo; lactose 20mg
Active Comparator: linaclotide; linaclotide 290 ug over-encapsulated identical appearance to placebo	Drug: Linaclotide 290 micrograms; linaclotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Small Bowel Water Content AUC 0-6hours	Area under curve Small Bowel Water Content	from enrolment until study end at approximately 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Small Bowel Water Content (SBWC)	change in SBWC after second meal from T300 to T360 ( ∆ SBWC),	from enrolment until study end at approximately 4 weeks
Orocaecal transit time (OCTT)	Time from meal ingestion to appearance of head of meal in caecum	from enrolment until study end at approximately 4 weeks
T1 ascending colon	T1 ascending colon(T1AC), a measure of colonic water content.	from enrolment until study end at approximately 4 weeks

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Cystic Fibrosis Trust

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: August 5, 2026
• First Submitted That Met QC Criteria: August 18, 2026
• First Posted (Actual): August 21, 2026

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: MRI; cystic fibrosis; linaclotide
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis
• Other Study ID Numbers: FMHS 185-0526

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified information may be shared on request
• IPD Sharing Time Frame: May 2027 for 7 years
• IPD Sharing Access Criteria: Access via principle investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No