Cystic Fibrosis (CF)Early Phase 1MODELNCT07569419
Proof of Principle Study for an Efficacy Trial of Linaclotide for Cystic Fibrosis
A Early Phase 1 study testing Linaclotide 290 micrograms in people with Cystic Fibrosis (CF), run by University of Nottingham at 1 site in United Kingdom.
Trial summary
Linaclotide is a medicine used to treat constipation and irritable bowel syndrome with constipation (IBS-C). It works by acting on the surface of the gut lining, where it increases the movement of salt and water into the bowel. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis (CF)
- What is being tested?
- Linaclotide 290 micrograms
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Mar 2026to Oct 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participant is willing and able to give informed consent for participation in the study
- Not currently taking any medications (except for selective serotonin reuptake inhibitors, low dose tricyclic antidepressants, antihistamines, and oral contraceptive pill).
- 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 rice pudding/blue dye meal, and rating stool frequency and appearance.
Who cannot join
- Contraindication to MRI scanning (i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury, unable to lie flat and relatively still for less than 5 minutes.)
- Pregnancy, lactating, or planning pregnancy during the investigation declared by candidate.
- History declared by the candidate of pre-existing gastrointestinal disorder that may affect bowel function.
- Reported history of previous resection of the oesophagus, stomach, or intestine (excluding appendix).
- Intestinal stoma.
- Any medical condition that may potentially compromise participation in the study e.g., known food intolerance to rice pudding, known contraindication to the oral administration of linaclotide or placebo.
Show all 14Show fewer
- Has a body mass index (BMI) value less than 18.5 or greater than 35.
- Will not agree to follow dietary and lifestyle restrictions required.
- Unable to stop drugs known to alter GI motility including mebeverine, opiates, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists for the duration of the study.
- Participants who are currently (or in the past 3 months) taking antibiotics or probiotics as these may impact GI function.
- Participation in night shift work the week prior to the study day. Night work is defined as working between midnight and 6.00 AM.
- Anyone who in the opinion of the investigator is unlikely to be able to comply with the protocol e.g., cognitive dysfunction, chaotic lifestyle related to substance abuse.
- Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance
- -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Sir Peter Mansfield Imaging Centre
Nottingham, NG7 2QX
Mahbuba Amhed, 0115 95 14747, Mahbuba.Ahmed@nottingham.ac.uk
About this study
Official title: A Randomised, Placebo-controlled Crossover Study Defining the Mode of Action of Linaclotide in Healthy Volunteers Using MRI
Linaclotide is a medicine used to treat constipation and irritable bowel syndrome with constipation (IBS-C). It works by acting on the surface of the gut lining, where it increases the movement of salt and water into the bowel. This softens stools, makes them easier to pass, and can also reduce gut pain
One advantage of linaclotide is that, unlike some natural substances in the gut, it is stable and can act throughout the intestine. Studies in animals show that it has the strongest effect in the upper small intestine, but it may act in other parts of the bowel as well. In people, however, it is not yet clear whether linaclotide mainly works in the small intestine or in the large intestine (colon). Knowing this is important, because it could help the investigators understand whether linaclotide might also be useful in other conditions, such as cystic fibrosis, where the gut does not handle fluid properly.
Read more
Linaclotide is taken as a capsule, but less than 1% is absorbed into the bloodstream. Instead, it stays in the gut, where it is broken down into smaller active parts. This means both the small intestine and colon may be exposed to its effects.
Until now, it has been hard to study this because traditional methods only measure one part of the gut at a time. A team at the University of Nottingham has developed MRI scanning methods that can safely and non-invasively measure water content in the small intestine and colon.
The aim of this pilot study is to use MRI in healthy volunteers to see exactly where linaclotide acts. This knowledge will help optimise future studies in conditions such as cystic fibrosis.
Read the detailed description
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In CF, defective CFTR may lead to various clinical effects on the gastrointestinal (GI) system; indeed, many CF patients report significant GI symptoms, with the most frequent being attributable to the lower GI tract, including bloating, flatulence, abdominal pain, and borborygmi. Moreover, constipation is another prevalent GI symptom in CF patients. It is estimated that 10-57% of CF patients report constipation symptoms, with an even higher prevalence (approximately 73%) in adults over the age of 30. Symptoms such as constipation are hypothesised to occur due to decreased luminal fluid content resulting from a reduction in anion flow, which ultimately leads to increased amounts of viscous mucus and slowed transit of intestinal contents. Presently, these GI symptoms in CF patients are often treated with laxatives and enemas, and in some cases surgical treatment, which can be uncomfortable and invasive, suggesting that alternative treatments are required.
Linaclotide, a drug approved for safe use across Europe and in the UK, is a synthetic analogue of uroguanylin that activates guanylate cyclase-C (GC-C) receptors located on the luminal surface of intestinal epithelial cells. Activation of GC-C increases intracellular cyclic guanosine monophosphate (cGMP), which stimulates cGMP-dependent protein kinase II (PKGII) and protein kinase A (PKA). Collectively, these kinases activate CFTR, leading to chloride and water secretion into the intestinal lumen. In parallel, elevated cGMP inhibits the sodium-hydrogen exchanger 3 (NHE3), thereby reducing sodium and water absorption. Together, these actions promote fluid secretion and accelerate intestinal transit, leading to linaclotide being commonly prescribed for the treatment of chronic idiopathic constipation and irritable bowel syndrome with chronic constipation (IBS-C).
Meta-analyses confirm linaclotide's clinical benefit in chronic idiopathic constipation and IBS-C; however, its role in CF remains uncertain, though anecdotal reports and animal models suggest therapeutic potential. Linaclotide has less than 1% systemic bioavailability and is degraded in the upper small bowel by carboxypeptidases to an active metabolite, with a small proportion of the administered dose recovered in stool, providing exposure throughout the small and large intestine. However, the primary site of action in humans remains undefined.
Traditional perfusion methods provide only segmental information, limiting assessment of the whole intestine. By contrast, magnetic resonance imaging (MRI) enables non-invasive evaluation of gastrointestinal water content across multiple regions. The Nottingham group has validated MRI techniques for quantifying small bowel water content and assessing colonic chyme hydration via T1 mapping. These methods have been successfully applied to study the effects of various pharmacological agents on gastrointestinal function.
Aim: To define the site of action of linaclotide in healthy volunteers using MRI. Identifying the regional effects of linaclotide will help optimise its future evaluation in CF patients. Based on clinical observations in constipation, stool effects emerge within seven days; however, the investigators hypothesise that small bowel changes occur within 1-2 hours of dosing. Therefore, a one-day pre-dosing regimen is expected to elicit a measurable effect on both the small bowel and colon while minimising participant burden.
Subjects will take 290ug linaclotide /placebo on the day prior to study day (day -1) and on the study day
- Conditions
- Cystic Fibrosis (CF)
- Being tested
- Linaclotide 290 micrograms, Lactose placebo pill
- Keywords
- linaclotide, cystic fibrosis, gastrointestinal, MRI
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linaclotide 290 microgramsDrug
290 mcg, 2 days dosing, oral capsule form
Lactose placebo pillDrug
Placebo form, oral capsules identical to linaclotide
| Study group | Role | What they receive |
|---|---|---|
| Linaclotide | Experimental | 290 mcg linaclotide across 2 days Receives: Drug: Linaclotide 290 micrograms |
| Placebo | Placebo comparator | Lactose placebo Receives: Drug: Lactose placebo pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Small bowel water content
Area under curve (AUC) 0-360 minutes Water content in small bowel as assessed by MRI (mL)
Measured: Baseline, and 0, 60, 120, 180, 240, 300, 360 minutes post-dose
Secondary outcomes (7)
Colon water content
Area under curve (AUC) 0-360 min Water content in the ascending colonic region as assessed by MRI (mL)
Measured: Baseline, and 0, 60, 120, 180, 240, 300, 360 minutes post-dose
Colonic regional segmental volumes
Total volume of regional colonic segments (ascending, transverse, descending, sigmorectal) as assessed by MRI (mL) at each time point.
Measured: Baseline, and 0, 60, 120, 180, 240, 300, 360 minutes post-dose
Changes in stool consistency
Stool consistency rated using Bristol stool scale (type 1-7; 7 being watery stool).
Measured: 2 days before intervention, 5 days post-intervention
Changes in whole gut transit time (WGTT)
Assessed by time to stool discolouration following administration of blue dye paste.
Measured: 1 day post-intervention
Gastrointestinal symptom rating
Assessing the severity of common gastrointestinal symptoms (flatulence / gas passage, diarrhoea / loose stool, bloating, abdominal pain) via Likert-type scale: 0 = not at all
- = mild (distinct but negligible)
- = moderate (annoying)
- = severe (disabling
Measured: 2 days pre-intervention and 5 days post-intervention
Changes in stool frequency
Frequency (per day) of bowel movements (number with exact time)
Measured: 2 days before starting intervention and for 5 days post intervention
Small bowel motility
Maximum motility score (A.U) of the small bowel as assessed by MRI
Measured: Baseline, and 0, 60, 120, 180, 240, 300, 360 minutes post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2026
- Study start9 Mar 2026
- Primary completionAug 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Cystic Fibrosis (CF)Studies 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
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robin Spiller, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07569419
- Sponsor's protocol ID
- FMHS-10-1025
- Acronym
- MODEL
- Status last verified
- Apr 2026
- First submitted
- 15 Dec 2025
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Wilkinson-Smith, V., Hoad, C., Atkinson, D., Marciani, L., Corsetti, M., Scott, S. M., Taylor, S., Gowland, P., & Spiller, R. (2021). O59 MRI methods to define colonic function in health and constipation. Gut, 70(Suppl 1), A32-A33. https://doi.org/10.1136/GUTJNL-2020-BSGCAMPUS.59
Stefano MA, Sandy NS, Zagoya C, Duckstein F, Ribeiro AF, Mainz JG, Lomazi EA. Diagnosing constipation in patients with cystic fibrosis applying ESPGHAN criteria. J Cyst Fibros. 2022 May;21(3):497-501. doi: 10.1016/j.jcf.2021.08.021. Epub 2021 Sep 9. No abstract available.
PubMed 34511390Stefano MA, Poderoso RE, Mainz JG, Ribeiro JD, Ribeiro AF, Lomazi EA. Prevalence of constipation in cystic fibrosis patients: a systematic review of observational studies. J Pediatr (Rio J). 2020 Nov-Dec;96(6):686-692. doi: 10.1016/j.jped.2020.03.004. Epub 2020 May 8.
PubMed 32389617Rubinstein S, Moss R, Lewiston N. Constipation and meconium ileus equivalent in patients with cystic fibrosis. Pediatrics. 1986 Sep;78(3):473-9.
PubMed 3748682McHugh DR, Cotton CU, Moss FJ, Vitko M, Valerio DM, Kelley TJ, Hao S, Jafri A, Drumm ML, Boron WF, Stern RC, McBennett K, Hodges CA. Linaclotide improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium/hydrogen exchanger 3. Am J Physiol Gastrointest Liver Physiol. 2018 Nov 1;315(5):G868-G878. doi: 10.1152/ajpgi.00261.2017. Epub 2018 Aug 17.
PubMed 30118317Marciani L, Wright J, Foley S, Hoad CL, Totman JJ, Bush D, Hartley C, Armstrong A, Manby P, Blackshaw E, Perkins AC, Gowland PA, Spiller RC. Effects of a 5-HT(3) antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2010 Sep;32(5):655-63. doi: 10.1111/j.1365-2036.2010.04395.x.
PubMed 20626735Marciani L, Garsed KC, Hoad CL, Fields A, Fordham I, Pritchard SE, Placidi E, Murray K, Chaddock G, Costigan C, Lam C, Jalanka-Tuovinen J, De Vos WM, Gowland PA, Spiller RC. Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI: comparison of split vs single dose. Neurogastroenterol Motil. 2014 Oct;26(10):1426-36. doi: 10.1111/nmo.12403. Epub 2014 Jul 24.
PubMed 25060551Luo M, Liu Y, Nikolovska K, Riederer B, Patrucco E, Hofmann F, Seidler U. cGMP-dependent kinase 2, Na+/H+ exchanger NHE3, and PDZ-adaptor NHERF2 co-assemble in apical membrane microdomains. Acta Physiol (Oxf). 2024 Apr;240(4):e14125. doi: 10.1111/apha.14125. Epub 2024 Mar 27.
PubMed 38533975Hayee B, Watson KL, Campbell S, Simpson A, Farrell E, Hutchings P, Macedo P, Perrin F, Whelan K, Elston C. A high prevalence of chronic gastrointestinal symptoms in adults with cystic fibrosis is detected using tools already validated in other GI disorders. United European Gastroenterol J. 2019 Aug;7(7):881-888. doi: 10.1177/2050640619841545.
PubMed 31428412Hannig G, Tchernychev B, Kurtz CB, Bryant AP, Currie MG, Silos-Santiago I. Guanylate cyclase-C/cGMP: an emerging pathway in the regulation of visceral pain. Front Mol Neurosci. 2014 Apr 16;7:31. doi: 10.3389/fnmol.2014.00031. eCollection 2014.
PubMed 24795564Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut. 2011 Feb;60(2):209-18. doi: 10.1136/gut.2010.227132.
PubMed 21205879Dellschaft N, Murray K, Ren Y, Marciani L, Gowland P, Spiller R, Hoad C. Assessing Water Content of the Human Colonic Chyme Using the MRI Parameter T1: A Key Biomarker of Colonic Function. Neurogastroenterol Motil. 2025 Apr;37(4):e14999. doi: 10.1111/nmo.14999. Epub 2025 Jan 10.
PubMed 39789944Dellschaft N, Hoad C, Marciani L, Gowland P, Spiller R. Small bowel water content assessed by MRI in health and disease: a collation of single-centre studies. Aliment Pharmacol Ther. 2022 Feb;55(3):327-338. doi: 10.1111/apt.16673. Epub 2021 Oct 30.
PubMed 34716925De Lisle RC, Borowitz D. The cystic fibrosis intestine. Cold Spring Harb Perspect Med. 2013 Sep 1;3(9):a009753. doi: 10.1101/cshperspect.a009753.
PubMed 23788646Corsetti M, Tack J. Linaclotide: A new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation. United European Gastroenterol J. 2013 Feb;1(1):7-20. doi: 10.1177/2050640612474446.
PubMed 24917937
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Placebo-controlled Crossover Study Defining the Mode of Action of Linaclotide in Healthy Volunteers Using MRI
- ClinicalTrials.gov ID
- NCT07569419
- Acronym / sponsor ID
- MODEL / FMHS-10-1025
- Conditions
- Cystic Fibrosis (CF)
- Keywords
- linaclotide, cystic fibrosis, gastrointestinal, MRI
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- 9 Mar 2026 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 6 May 2026 (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.
Linaclotide is a medicine used to treat constipation and irritable bowel syndrome with constipation (IBS-C). It works by acting on the surface of the gut lining, where it increases the movement of salt and water into the bowel. This softens stools, makes them easier to pass, and can also reduce gut pain
One advantage of linaclotide is that, unlike some natural substances in the gut, it is stable and can act throughout the intestine. Studies in animals show that it has the strongest effect in the upper small intestine, but it may act in other parts of the bowel as well. In people, however, it is not yet clear whether linaclotide mainly works in the small intestine or in the large intestine (colon). Knowing this is important, because it could help the investigators understand whether linaclotide might also be useful in other conditions, such as cystic fibrosis, where the gut does not handle fluid properly.
Linaclotide is taken as a capsule, but less than 1% is absorbed into the bloodstream. Instead, it stays in the gut, where it is broken down into smaller active parts. This means both the small intestine and colon may be exposed to its effects.
Until now, it has been hard to study this because traditional methods only measure one part of the gut at a time. A team at the University of Nottingham has developed MRI scanning methods that can safely and non-invasively measure water content in the small intestine and colon.
The aim of this pilot study is to use MRI in healthy volunteers to see exactly where linaclotide acts. This knowledge will help optimise future studies in conditions such as cystic fibrosis.
Detailed description
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In CF, defective CFTR may lead to various clinical effects on the gastrointestinal (GI) system; indeed, many CF patients report significant GI symptoms, with the most frequent being attributable to the lower GI tract, including bloating, flatulence, abdominal pain, and borborygmi. Moreover, constipation is another prevalent GI symptom in CF patients. It is estimated that 10-57% of CF patients report constipation symptoms, with an even higher prevalence (approximately 73%) in adults over the age of 30. Symptoms such as constipation are hypothesised to occur due to decreased luminal fluid content resulting from a reduction in anion flow, which ultimately leads to increased amounts of viscous mucus and slowed transit of intestinal contents. Presently, these GI symptoms in CF patients are often treated with laxatives and enemas, and in some cases surgical treatment, which can be uncomfortable and invasive, suggesting that alternative treatments are required.
Linaclotide, a drug approved for safe use across Europe and in the UK, is a synthetic analogue of uroguanylin that activates guanylate cyclase-C (GC-C) receptors located on the luminal surface of intestinal epithelial cells. Activation of GC-C increases intracellular cyclic guanosine monophosphate (cGMP), which stimulates cGMP-dependent protein kinase II (PKGII) and protein kinase A (PKA). Collectively, these kinases activate CFTR, leading to chloride and water secretion into the intestinal lumen. In parallel, elevated cGMP inhibits the sodium-hydrogen exchanger 3 (NHE3), thereby reducing sodium and water absorption. Together, these actions promote fluid secretion and accelerate intestinal transit, leading to linaclotide being commonly prescribed for the treatment of chronic idiopathic constipation and irritable bowel syndrome with chronic constipation (IBS-C).
Meta-analyses confirm linaclotide's clinical benefit in chronic idiopathic constipation and IBS-C; however, its role in CF remains uncertain, though anecdotal reports and animal models suggest therapeutic potential. Linaclotide has less than 1% systemic bioavailability and is degraded in the upper small bowel by carboxypeptidases to an active metabolite, with a small proportion of the administered dose recovered in stool, providing exposure throughout the small and large intestine. However, the primary site of action in humans remains undefined.
Traditional perfusion methods provide only segmental information, limiting assessment of the whole intestine. By contrast, magnetic resonance imaging (MRI) enables non-invasive evaluation of gastrointestinal water content across multiple regions. The Nottingham group has validated MRI techniques for quantifying small bowel water content and assessing colonic chyme hydration via T1 mapping. These methods have been successfully applied to study the effects of various pharmacological agents on gastrointestinal function.
Aim: To define the site of action of linaclotide in healthy volunteers using MRI. Identifying the regional effects of linaclotide will help optimise its future evaluation in CF patients. Based on clinical observations in constipation, stool effects emerge within seven days; however, the investigators hypothesise that small bowel changes occur within 1-2 hours of dosing. Therefore, a one-day pre-dosing regimen is expected to elicit a measurable effect on both the small bowel and colon while minimising participant burden.
Subjects will take 290ug linaclotide /placebo on the day prior to study day (day -1) and on the study day
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Linaclotide | Experimental | Drug: Linaclotide 290 micrograms290 mcg linaclotide across 2 days |
| Placebo | Placebo comparator | Drug: Lactose placebo pillLactose placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Participant is willing and able to give informed consent for participation in the study
- Not currently taking any medications (except for selective serotonin reuptake inhibitors, low dose tricyclic antidepressants, antihistamines, and oral contraceptive pill).
- 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 rice pudding/blue dye meal, and rating stool frequency and appearance.
Key exclusion criteria (14 listed)
- Contraindication to MRI scanning (i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury, unable to lie flat and relatively still for less than 5 minutes.)
- Pregnancy, lactating, or planning pregnancy during the investigation declared by candidate.
- History declared by the candidate of pre-existing gastrointestinal disorder that may affect bowel function.
- Reported history of previous resection of the oesophagus, stomach, or intestine (excluding appendix).
- Intestinal stoma.
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 |
|---|---|---|
| Linaclotide 290 micrograms290 mcg, 2 days dosing, oral capsule form | Drug | Linaclotide |
| Lactose placebo pillPlacebo form, oral capsules identical to linaclotide | Drug | Placebo |
Primary outcome
Small bowel water content
Time frame: Baseline, and 0, 60, 120, 180, 240, 300, 360 minutes post-dose
Area under curve (AUC) 0-360 minutes Water content in small bowel as assessed by MRI (mL)
7 secondary outcomes
Colon water content
Time frame: Baseline, and 0, 60, 120, 180, 240, 300, 360 minutes post-dose
Colonic regional segmental volumes
Time frame: Baseline, and 0, 60, 120, 180, 240, 300, 360 minutes post-dose
Changes in stool consistency
Time frame: 2 days before intervention, 5 days post-intervention
Changes in whole gut transit time (WGTT)
Time frame: 1 day post-intervention
Gastrointestinal symptom rating
Time frame: 2 days pre-intervention and 5 days post-intervention
Changes in stool frequency
Time frame: 2 days before starting intervention and for 5 days post intervention
Small bowel motility
Time frame: Baseline, and 0, 60, 120, 180, 240, 300, 360 minutes post-dose
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- BackgroundWilkinson-Smith, V., Hoad, C., Atkinson, D., Marciani, L., Corsetti, M., Scott, S. M., Taylor, S., Gowland, P., & Spiller, R. (2021). O59 MRI methods to define colonic function in health and constipation. Gut, 70(Suppl 1), A32-A33. https://doi.org/10.1136/GUTJNL-2020-BSGCAMPUS.59
- Background: PubMed 34511390Stefano MA, Sandy NS, Zagoya C, Duckstein F, Ribeiro AF, Mainz JG, Lomazi EA. Diagnosing constipation in patients with cystic fibrosis applying ESPGHAN criteria. J Cyst Fibros. 2022 May;21(3):497-501. doi: 10.1016/j.jcf.2021.08.021. Epub 2021 Sep 9. No abstract available.
- Background: PubMed 32389617Stefano MA, Poderoso RE, Mainz JG, Ribeiro JD, Ribeiro AF, Lomazi EA. Prevalence of constipation in cystic fibrosis patients: a systematic review of observational studies. J Pediatr (Rio J). 2020 Nov-Dec;96(6):686-692. doi: 10.1016/j.jped.2020.03.004. Epub 2020 May 8.
- Background: PubMed 3748682Rubinstein S, Moss R, Lewiston N. Constipation and meconium ileus equivalent in patients with cystic fibrosis. Pediatrics. 1986 Sep;78(3):473-9.
- Background: PubMed 30118317McHugh DR, Cotton CU, Moss FJ, Vitko M, Valerio DM, Kelley TJ, Hao S, Jafri A, Drumm ML, Boron WF, Stern RC, McBennett K, Hodges CA. Linaclotide improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium/hydrogen exchanger 3. Am J Physiol Gastrointest Liver Physiol. 2018 Nov 1;315(5):G868-G878. doi: 10.1152/ajpgi.00261.2017. Epub 2018 Aug 17.
- Background: PubMed 20626735Marciani L, Wright J, Foley S, Hoad CL, Totman JJ, Bush D, Hartley C, Armstrong A, Manby P, Blackshaw E, Perkins AC, Gowland PA, Spiller RC. Effects of a 5-HT(3) antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2010 Sep;32(5):655-63. doi: 10.1111/j.1365-2036.2010.04395.x.
- Background: PubMed 25060551Marciani L, Garsed KC, Hoad CL, Fields A, Fordham I, Pritchard SE, Placidi E, Murray K, Chaddock G, Costigan C, Lam C, Jalanka-Tuovinen J, De Vos WM, Gowland PA, Spiller RC. Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI: comparison of split vs single dose. Neurogastroenterol Motil. 2014 Oct;26(10):1426-36. doi: 10.1111/nmo.12403. Epub 2014 Jul 24.
- Background: PubMed 38533975Luo M, Liu Y, Nikolovska K, Riederer B, Patrucco E, Hofmann F, Seidler U. cGMP-dependent kinase 2, Na+/H+ exchanger NHE3, and PDZ-adaptor NHERF2 co-assemble in apical membrane microdomains. Acta Physiol (Oxf). 2024 Apr;240(4):e14125. doi: 10.1111/apha.14125. Epub 2024 Mar 27.
- Background: PubMed 31428412Hayee B, Watson KL, Campbell S, Simpson A, Farrell E, Hutchings P, Macedo P, Perrin F, Whelan K, Elston C. A high prevalence of chronic gastrointestinal symptoms in adults with cystic fibrosis is detected using tools already validated in other GI disorders. United European Gastroenterol J. 2019 Aug;7(7):881-888. doi: 10.1177/2050640619841545.
- Background: PubMed 24795564Hannig G, Tchernychev B, Kurtz CB, Bryant AP, Currie MG, Silos-Santiago I. Guanylate cyclase-C/cGMP: an emerging pathway in the regulation of visceral pain. Front Mol Neurosci. 2014 Apr 16;7:31. doi: 10.3389/fnmol.2014.00031. eCollection 2014.
- Background: PubMed 21205879Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut. 2011 Feb;60(2):209-18. doi: 10.1136/gut.2010.227132.
- Background: PubMed 39789944Dellschaft N, Murray K, Ren Y, Marciani L, Gowland P, Spiller R, Hoad C. Assessing Water Content of the Human Colonic Chyme Using the MRI Parameter T1: A Key Biomarker of Colonic Function. Neurogastroenterol Motil. 2025 Apr;37(4):e14999. doi: 10.1111/nmo.14999. Epub 2025 Jan 10.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Linaclotide 290 micrograms in people with Cystic Fibrosis (CF), 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 4 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 6 May 2026. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Josh Thorley, PhD (07342646598, josh.thorley@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Small bowel water content (time frame: Baseline, and 0, 60, 120, 180, 240, 300, 360 minutes post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07569419, which also lists 19 linked publications.
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 6 May 2026.