Cytosponge for Gastric Intestinal Metaplasia (CyGIM)

May 6, 2024 updated by: Massimiliano di Pietro, MD, University of Cambridge

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

226

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Massimiliano di Pietro, MD
  • Phone Number: 01223763349
  • Email: md460@cam.ac.uk

Study Contact Backup

  • Name: Andreas Hadjinicolaou, MD PhD
  • Phone Number: 01223763349
  • Email: ah499@cam.ac.uk

Study Locations

  • United Kingdom
      • Cambridge, United Kingdom, CB20QQ
        • Recruiting
        • Cambridge Clinical Research Centre
        • Contact:
        • Sub-Investigator:
          • Andreas Hadjinicolaou, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
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.
Other Names:
  • Blood sampling
  • Upper GI endoscopy
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
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.
Other Names:
  • Blood sampling
  • Upper GI endoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity of Cytosponge for GIM
Time Frame: 2 months
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
Time Frame: through study completion, an average of 1 year
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
Time Frame: 2 weeks from recruitment
Adverse events realted to Cytosponge will be recorded immediate after administration and at 2 weeks after study visit
2 weeks from recruitment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cambridge

Collaborators

University College London Hospitals
Nottingham University Hospitals NHS Trust

Investigators

  • Principal Investigator: Massimiliano di Pietro, MD, Early Cancer Institute, University of Cambridge
  • Study Director: Andreas Hadjicinolaou, MD PhD, Early Cancer Institute, University of Cambridge

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2023

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

November 30, 2022

First Submitted That Met QC Criteria

December 9, 2022

First Posted (Actual)

December 20, 2022

Study Record Updates

Last Update Posted (Actual)

May 8, 2024

Last Update Submitted That Met QC Criteria

May 6, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CyGIM_v1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Patient details will be pseudo-anonymised, with no identifiable information to be shared outside the clinical research team. Electronic transfers of pseudo-anonymised data will meet industry and NHS-mandated standards including encryption to at least Advanced Encryption Standard (AES) 256. Data will be stored on study database for 10 yrs after study completion, in a linked anonymised manner. Participants will be aware that their PID might be accessed by external regulatory bodies for the purposes of assessing legal compliance and meeting relevant regulatory obligations. Anonymised clinical and lifestyle information may be transferred and stored in international repositories for access by international researchers in line with patient consent.

Temporary access to PID might occur in the event of pathology review by central pathology panel, but PID will not be stored outside local research institution.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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