Cytosponge for Gastric Intestinal Metaplasia

NCT05657080 | Recruiting FDA Device

• 1 other identifier: CyGIM_v1
• Study Type: observational
• Target: 226
• Locations: 1 country
• Sites: 1

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

Conditions

Gastric Cancer; Gastric Intestinal Metaplasia; Gastric Atrophy

Keywords

early cancer detection; gastric premalignant lesions; non-invasive cancer screening

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Histopathological disease stage

  through study completion, an average of 1 year

• Number of participants with device-related adverse events as assessed by CTCAE v4.0

  2 weeks from recruitment

Study Arms (2)

Cases

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

Controls

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

Interventions

Cytosponge-TFF3 DEVICE

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.

Also known as: Upper GI endoscopy, Blood sampling

Cases; Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Cambridge: lead
• University College London Hospitals: collaborator
• Nottingham University Hospitals NHS Trust: collaborator

Study Sites (1)

Cambridge Clinical Research Centre

Cambridge, CB20QQ, United Kingdom

RECRUITING

Related 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.

  PMID: 31278206 BACKGROUND

• 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.

  PMID: 30841008 BACKGROUND

• 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.

  PMID: 32738955 BACKGROUND

• 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.

  PMID: 25634542 BACKGROUND

• 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.

  PMID: 34358719 BACKGROUND

• 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.

  PMID: 23335180 BACKGROUND

• 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.

  PMID: 27265836 BACKGROUND

• 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.

  PMID: 31816300 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Human tissue obtained in this study will include: 1. Upper gastrointestinal tract tissue from endoscopic biopsy samples for the purpose of tissue diagnosis and for discovery validation of molecular biomarkers 2. Blood 3. Gastric juice (via Cytosponge \[as supernatant\] or via endoscopic aspiration) 4. Gastric cytology (via Cytosponge) Nucleic acids (DNA/RNA) will be extracted from tissue biopsies, gastric juice vesicles and blood.

MeSH Terms

Conditions

Stomach Neoplasms; Gastritis, Atrophic

Interventions

Endoscopy, Digestive System; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastritis; Gastroenteritis

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Specimen Handling; Clinical Laboratory Techniques; Punctures; Investigative Techniques

Study Officials

• Massimiliano di Pietro, MD

  University of Cambridge

  PRINCIPAL INVESTIGATOR

• Andreas Hadjicinolaou, MD PhD

  University of Cambridge

  STUDY DIRECTOR

Central Study Contacts

Massimiliano di Pietro, MD

CONTACT

01223763349; md460@cam.ac.uk

Andreas Hadjinicolaou, MD PhD

CONTACT

01223763349; ah499@cam.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Clinical Investigator Scientist

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: December 20, 2022
• Study Start: October 16, 2023
• Primary Completion: September 30, 2024
• Study Completion: December 31, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

GB (1)