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.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
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.
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- 適用できない
連絡先と場所
研究連絡先
研究連絡先
- 名前：Abi Spicer, PhD
- 電話番号：+44-7855 193162
- メール：MS-fempto@nottingham.ac.uk
研究場所
-
-
Gloucestershire
-
Nottingham、Gloucestershire、イギリス、NG7 2UH
- Sir Peter Mansfield Imaging Centre
-
コンタクト：
- Abi Spicer, PhD
- 電話番号：+447855 193162
- メール：MS-fempto@nottingham.ac.uk
-
コンタクト：
- Robin Spiller, MD
- 電話番号：+44-7824328319
- メール：robin.spiller@nottingham.ac.uk
-
-
参加基準
適格基準
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：トリプル
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
プラセボコンパレーター：Placebo
encapsulated lactose
|
lactose 20mg
|
|
アクティブコンパレータ：linaclotide
linaclotide 290 ug over-encapsulated identical appearance to placebo
|
linaclotide
|
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Small Bowel Water Content AUC 0-6hours
時間枠：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
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Small Bowel Water Content (SBWC)
時間枠：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)
時間枠：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
時間枠：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
|
協力者と研究者
協力者
協力者
研究記録日
主要日程の研究
研究開始 (推定)
研究開始
一次修了 (推定)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
その他の研究ID番号
- FMHS 185-0526
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有時間枠
IPD 共有アクセス基準
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- CSR
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。