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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Abi Spicer, PhD
- Telefonní číslo: +44-7855 193162
- E-mail: MS-fempto@nottingham.ac.uk
Studijní místa
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-
Gloucestershire
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Nottingham, Gloucestershire, Spojené království, NG7 2UH
- Sir Peter Mansfield Imaging Centre
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Kontakt:
- Abi Spicer, PhD
- Telefonní číslo: +447855 193162
- E-mail: MS-fempto@nottingham.ac.uk
-
Kontakt:
- Robin Spiller, MD
- Telefonní číslo: +44-7824328319
- E-mail: robin.spiller@nottingham.ac.uk
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-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
Přijímá zdravé dobrovolníky
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Základní věda
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Trojnásobný
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Komparátor placeba: Placebo
encapsulated lactose
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lactose 20mg
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Aktivní komparátor: linaclotide
linaclotide 290 ug over-encapsulated identical appearance to placebo
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linaclotide
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Small Bowel Water Content AUC 0-6hours
Časové okno: from enrolment until study end at approximately 4 weeks
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Area under curve Small Bowel Water Content
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from enrolment until study end at approximately 4 weeks
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Change in Small Bowel Water Content (SBWC)
Časové okno: from enrolment until study end at approximately 4 weeks
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change in SBWC after second meal from T300 to T360 ( ∆ SBWC),
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from enrolment until study end at approximately 4 weeks
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Orocaecal transit time (OCTT)
Časové okno: from enrolment until study end at approximately 4 weeks
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Time from meal ingestion to appearance of head of meal in caecum
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from enrolment until study end at approximately 4 weeks
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T1 ascending colon
Časové okno: from enrolment until study end at approximately 4 weeks
|
T1 ascending colon(T1AC), a measure of colonic water content.
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from enrolment until study end at approximately 4 weeks
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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- FMHS 185-0526
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Popis plánu IPD
Časový rámec sdílení IPD
Kritéria přístupu pro sdílení IPD
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- CSR
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