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.
Обзор исследования
Статус
Условия
Вмешательство/лечение
Подробное описание
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.
Тип исследования
Регистрация (Оцененный)
Фаза
- Непригодный
Контакты и местонахождение
Контакты исследования
- Имя: Abi Spicer, PhD
- Номер телефона: +44-7855 193162
- Электронная почта: MS-fempto@nottingham.ac.uk
Места учебы
-
-
Gloucestershire
-
Nottingham, Gloucestershire, Соединенное Королевство, NG7 2UH
- Sir Peter Mansfield Imaging Centre
-
Контакт:
- Abi Spicer, PhD
- Номер телефона: +447855 193162
- Электронная почта: MS-fempto@nottingham.ac.uk
-
Контакт:
- Robin Spiller, MD
- Номер телефона: +44-7824328319
- Электронная почта: robin.spiller@nottingham.ac.uk
-
-
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
Принимает здоровых добровольцев
Описание
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.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Фундаментальная наука
- Распределение: Рандомизированный
- Интервенционная модель: Назначение кроссовера
- Маскировка: Тройной
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Плацебо Компаратор: Placebo
encapsulated lactose
|
lactose 20mg
|
|
Активный компаратор: linaclotide
linaclotide 290 ug over-encapsulated identical appearance to placebo
|
linaclotide
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Small Bowel Water Content AUC 0-6hours
Временное ограничение: from enrolment until study end at approximately 4 weeks
|
Area under curve Small Bowel Water Content
|
from enrolment until study end at approximately 4 weeks
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Change in Small Bowel Water Content (SBWC)
Временное ограничение: from enrolment until study end at approximately 4 weeks
|
change in SBWC after second meal from T300 to T360 ( ∆ SBWC),
|
from enrolment until study end at approximately 4 weeks
|
|
Orocaecal transit time (OCTT)
Временное ограничение: from enrolment until study end at approximately 4 weeks
|
Time from meal ingestion to appearance of head of meal in caecum
|
from enrolment until study end at approximately 4 weeks
|
|
T1 ascending colon
Временное ограничение: from enrolment until study end at approximately 4 weeks
|
T1 ascending colon(T1AC), a measure of colonic water content.
|
from enrolment until study end at approximately 4 weeks
|
Соавторы и исследователи
Спонсор
Соавторы
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- FMHS 185-0526
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Описание плана IPD
Сроки обмена IPD
Критерии совместного доступа к IPD
Совместное использование IPD Поддерживающий тип информации
- STUDY_PROTOCOL
- КСО
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .