Cytosponge for Gastric Intestinal Metaplasia

Study Overview
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Brief Summary
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Gastric cancer has a very poor prognosis. The disease is often diagnosed at a late stage, when curative treatment options are limited or ineffective. There is a condition that predisposes to gastric cancer, known in medical terms as Gastric intestinal metaplasia (GIM). This pre-cancerous condition can be diagnosed with an endoscopic camera test, but it often very subtle and can be missed at routine endoscopy. There is evidence that about 7% of gastric cancers are missed at previous endoscopy. The Cytosponge-trefoil factor 3 (TFF-3) is a pill on a string combined to a molecular biomarker which could help early diagnosis of gastric cancer and GIM. Cytosponge-TFF3 has been showed in previous research to be useful to diagnose Barrett's oesophagus, a condition of the food pipe similar to GIM. The aim of this study is to investigate the utility of the Cytosponge in combination with molecular biomakers to diagnose GIM

Detailed Description
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This is a case-control study whose goal is to compare the non-endoscopic test (Cytosponge-TFF3) to standard endoscopy to diagnose gastric intestinal metaplasia (GIM), a precursor lesion for gastric cancer. The main objective of the study is to determine the sensitivity and specificity of the Cytosponge-TFF3 to detect gastric intestinal metaplasia (GIM) affecting the proximal stomach. In parallel to this clinical study, a experimental study will be carried out aimed at evaluating the utility of molecular biomarkers to refine/improve the diagnostic accuracy of the Cytosponge test. The hypothesis is that the non-invasive Cytosponge, in combination with molecular biomarkers, can accurately detect GIM to the same extent as conventional, but more invasive, endoscopic procedures. Patients will be invited to participate in the study if they are due their surveillance endoscopy, because they have the disease of interest (GIM or GC; cases) or have been referred for an upper endoscopy for abdominal complaint (controls). On the day of the endoscopy the patient will swallow the Cytosponge under supervision of a trained research nurse prior to the endoscopic procedure. The participant will also provide information on demographics, clinical exposures (alcohol, tobacco, drugs), have measurements of weight and height taken and they will also complete a validated gastrointestinal symptoms questionnaire. A blood sample will be taken from the cannula used for the sedatives or through venepuncture. The patients will then undergo their planned endoscopy with additional sampling of gastric juice (suctioned through the endoscope) and some additional research biopsies in addition to a standardized clinical protocol to diagnose GIM. The above research procedures will be performed prior and during the endoscopy. No further research procedures will follow afterwards beyond the day of the endoscopy. The aim is to develop a non-invasive test which can be used to screen patients at risk for GIM to allow early detection and treatment of pre-cancerous gastric lesions and ultimately reduce the number of patients dying of gastric cancer.

Official Title
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An Investigation on Cytosponge and Molecular Biomarkers to Identify Patients With Gastric Intestinal Metaplasia (GIM)

Conditions
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Gastric Cancer, Gastric Intestinal Metaplasia, Gastric Atrophy

Intervention / Treatment
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* Device: Cytosponge-TFF3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any participant 18 years and above clinically fit for an endoscopy with GIM of the proximal stomach confirmed on previous biopsies or gastric adenocarcinoma of intestinal type (cases) Any participant 18 years and above clinically fit for an endoscopy with upper GI symptoms leading to referral for endoscopy (controls) Ability to provide informed consent Exclusion Criteria: Individuals with a diagnosis of an oro-pharynx, oesophageal or gastro-oesophageal tumour (T2 staging and above), or symptoms of dysphagia. Patients with previous diagnosis of Barrett's oesophagus oesophageal varices, stricture or requiring dilatation of the oesophagus. Patients unable to stop anticoagulation therapy/medication timely before the procedure (heparin or tinzaparin, apixaban, rivaroxaban, dabigatran, edoxaban; 48 hours, warfarin; 5 days, clopidogrel; 7 days) Individuals who have had a myocardial infarction or any cardiac event less than six months ago. Individuals who have had a cerebrovascular event < 6 months ago where their swallowing has been affected Patients who have had previous treatments such as Photodynamic therapy (PDT), Radiofrequency ablation or Argon Plasma Coagulation for dysplastic Barrett's oesophagus Participants who are unable to provide informed consent. Participants under age 18. NB - Endoscopy is generally avoided in pregnant women and therefore it is unlikely that any pregnant women will be included although pregnancy would not be an absolute contraindication. Pregnancy/ pregnancy test will not be recorded as part of the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>This will include patients with: existing diagnosis of proximal GIM undergoing endoscopic surveillance a new diagnosis of proximal GIM requiring repeat endoscopy a historical diagnosis of GIM retrieved from the pathology records through retrospective analysis and lost in follow up gastric adenocarcinoma from upper GI multidisciplinary meeting. | Device: Cytosponge-TFF3<br>* Cytosponge is a less invasive procedure than endoscopy and consists of an expandable, spherical mesh, which is attached to a string and contained within a soluble capsule. Five minutes after swallowing (once the capsule has dissolved), the spherical mesh, which measures around 3cm in diameter can be retrieved by pulling on the string. Upon retrieval the Cytosponge scrapes against the surface of the top of the stomach and oesophagus and collect epithelial cells. The Cytosponge sample is then placed into a preservative fluid and the specimen is processed for molecular tests. Trefoil Factor 3 (TFF3) is a protein that is expressed in intestinal type epithelia of the gastrointestinal tract. TFF3 is the best biomarker, which can be coupled to the Cytosponge to diagnose intestinal metaplasia.<br>* Other names: Blood sampling;|
| Controls<br>Controls will be patients with no known premalignant conditions of the upper GI tract and fit to undergo an upper endoscopy. They will be recruited via standard referral routes for upper GI endoscopy due to upper GI symptoms via standard referral routes. Individuals must be able to provide informed consent. | Device: Cytosponge-TFF3<br>* Cytosponge is a less invasive procedure than endoscopy and consists of an expandable, spherical mesh, which is attached to a string and contained within a soluble capsule. Five minutes after swallowing (once the capsule has dissolved), the spherical mesh, which measures around 3cm in diameter can be retrieved by pulling on the string. Upon retrieval the Cytosponge scrapes against the surface of the top of the stomach and oesophagus and collect epithelial cells. The Cytosponge sample is then placed into a preservative fluid and the specimen is processed for molecular tests. Trefoil Factor 3 (TFF3) is a protein that is expressed in intestinal type epithelia of the gastrointestinal tract. TFF3 is the best biomarker, which can be coupled to the Cytosponge to diagnose intestinal metaplasia.<br>* Other names: Blood sampling;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of Cytosponge for GIM | Proportion of GIM cases extending to the proximal stomach diagnosed based on gold standard endoscopy with biopsies correclty classified by Cytosponge-TFF3 testing | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histopathological disease stage | A panel of clinical and molecular biomakers on biopsies, Cytosponge and blood, will be used to construct a model to predict the histopathological stage of disease (OLGA/OLGIM + grade of neoplasia) | through study completion, an average of 1 year | 
| Number of participants with device-related adverse events as assessed by CTCAE v4.0 | Adverse events realted to Cytosponge will be recorded immediate after administration and at 2 weeks after study visit | 2 weeks from recruitment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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early cancer detection, gastric premalignant lesions, non-invasive cancer screening