Clinical trial NCT05657080: Cytosponge for Gastric Intestinal Metaplasia
Official title: An Investigation on Cytosponge and Molecular Biomarkers to Identify Patients With Gastric Intestinal Metaplasia (GIM)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gastric Cancer
Gastric Intestinal Metaplasia
Gastric Atrophy
Keywords: early cancer detection
gastric premalignant lesions
non-invasive cancer screening
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: University College London Hospitals
name: Nottingham University Hospitals NHS Trust
First posted: 2022-12-20
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cases and controls will be treated in the UK.

Cases:

* Patients with an existing diagnosis of proximal GIM referred for endoscopic surveillance will
* Patients with newly diagnosed GIM who require a repeat endoscopy for complete endoscopy biopsy mapping.
* Patients with a historical diagnosis of GIM retrieved from the pathology records and in need of endoscopic surveillance based on clinical guidelines.
* Patients with gastric cancer (intestinal type) recruited from the multidisciplinary team meeting and undergoing endoscopy and laparoscopy as part of their regular cancer staging or surveillance.

Controls will be referred from primary or secondary care with upper GI symptoms and no known premalignant conditions of the upper GI tract.

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Sensitivity of Cytosponge for GIM
timeFrame: 2 months
Secondary outcomes:
measure: Histopathological disease stage
timeFrame: through study completion, an average of 1 year
measure: Number of participants with device-related adverse events as assessed by CTCAE v4.0
timeFrame: 2 weeks from recruitment
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge Clinical Research Centre
Study officials:
affiliation: University of Cambridge
name: Massimiliano di Pietro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cambridge
name: Andreas Hadjicinolaou, MD PhD
role: STUDY_DIRECTOR
References:
citation: Banks M, Graham D, Jansen M, Gotoda T, Coda S, di Pietro M, Uedo N, Bhandari P, Pritchard DM, Kuipers EJ, Rodriguez-Justo M, Novelli MR, Ragunath K, Shepherd N, Dinis-Ribeiro M. British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut. 2019 Sep;68(9):1545-1575. doi: 10.1136/gutjnl-2018-318126. Epub 2019 Jul 5.
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citation: Ross-Innes CS, Debiram-Beecham I, O'Donovan M, Walker E, Varghese S, Lao-Sirieix P, Lovat L, Griffin M, Ragunath K, Haidry R, Sami SS, Kaye P, Novelli M, Disep B, Ostler R, Aigret B, North BV, Bhandari P, Haycock A, Morris D, Attwood S, Dhar A, Rees C, Rutter MD, Sasieni PD, Fitzgerald RC; BEST2 Study Group. Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett's esophagus: a multi-center case-control study. PLoS Med. 2015 Jan 29;12(1):e1001780. doi: 10.1371/journal.pmed.1001780. eCollection 2015 Jan.
citation: Hadjinicolaou AV, Azizi AA, O'Donovan M, Debiram I, Fitzgerald RC, Di Pietro M. Cytosponge-TFF3 Testing can Detect Precancerous Mucosal Changes of the Stomach. Clin Gastroenterol Hepatol. 2022 Jun;20(6):1411-1412. doi: 10.1016/j.cgh.2021.07.047. Epub 2021 Aug 3.
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citation: Ikeda F, Shikata K, Hata J, Fukuhara M, Hirakawa Y, Ohara T, Mukai N, Nagata M, Yoshida D, Yonemoto K, Esaki M, Kitazono T, Kiyohara Y, Ninomiya T. Combination of Helicobacter pylori Antibody and Serum Pepsinogen as a Good Predictive Tool of Gastric Cancer Incidence: 20-Year Prospective Data From the Hisayama Study. J Epidemiol. 2016 Dec 5;26(12):629-636. doi: 10.2188/jea.JE20150258. Epub 2016 Jun 4.
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