Cytosponge for Gastric Intestinal Metaplasia

Gastric Cancer Clinical Trial

— CyGIM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05657080
• Other study ID #: CyGIM_v1
• Status: Recruiting
• Start date: October 16, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: University of Cambridge
• Contact: Massimiliano di Pietro, MD
• Phone: 01223763349
• Email: md460[@]cam.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 226
• Est. completion date: December 31, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Gastric Atrophy
• Gastric Cancer
• Gastric Intestinal Metaplasia
• Gastritis, Atrophic
• Metaplasia

Intervention

Device:
• Cytosponge-TFF3
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.

Locations

Country	Name	City	State
United Kingdom	Cambridge Clinical Research Centre	Cambridge

Sponsors (3)

Lead Sponsor	Collaborator
University of Cambridge	Nottingham University Hospitals NHS Trust, University College London Hospitals

Country where clinical trial is conducted

United Kingdom, 

References & Publications (8)

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. — View Citation

Cui L, Zhang X, Ye G, Zheng T, Song H, Deng H, Xiao B, Xia T, Yu X, Le Y, Guo J. Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer. Cancer. 2013 May 1;119(9):1618-26. doi: 10.1002/cncr.27903. Epub 2013 Jan 18. — View Citation

Fitzgerald RC, di Pietro M, O'Donovan M, Maroni R, Muldrew B, Debiram-Beecham I, Gehrung M, Offman J, Tripathi M, Smith SG, Aigret B, Walter FM, Rubin G; BEST3 Trial team; Sasieni P. Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial. Lancet. 2020 Aug 1;396(10247):333-344. doi: 10.1016/S0140-6736(20)31099-0. — View Citation

Gawron AJ, Shah SC, Altayar O, Davitkov P, Morgan D, Turner K, Mustafa RA. AGA Technical Review on Gastric Intestinal Metaplasia-Natural History and Clinical Outcomes. Gastroenterology. 2020 Feb;158(3):705-731.e5. doi: 10.1053/j.gastro.2019.12.001. Epub 2019 Dec 6. No abstract available. — View 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. — View 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. — View Citation

Pimentel-Nunes P, Libanio D, Marcos-Pinto R, Areia M, Leja M, Esposito G, Garrido M, Kikuste I, Megraud F, Matysiak-Budnik T, Annibale B, Dumonceau JM, Barros R, Flejou JF, Carneiro F, van Hooft JE, Kuipers EJ, Dinis-Ribeiro M. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy. 2019 Apr;51(4):365-388. doi: 10.1055/a-0859-1883. Epub 2019 Mar 6. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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