Stomach NeoplasmNCT04329299
Use of Blood Biomarkers to Predict Gastric Cancer Risk
An observational study of Stomach Neoplasm, run by National University Hospital, Singapore at 2 sites in Singapore.
Trial summary
This study aims to develop a cost-effective screening strategy for the Singapore population by targeted screening of people who have a high risk of stomach cancer, in order to detect early signs of the disease at a stage that can be prevented or cured. Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- Stomach Neoplasm
- What is being tested?
- blood-based biomarkers analyses
- How many people
- 6,862 participants
- Where
- 2 sitesSingapore
- Study dates
- 3 Dec 2012to 29 May 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients who have been referred to the participating study sites for upper GI endoscopy for standard clinical indications.
Who may be able to join
- The subject is greater than 40 years of age.
- The subject is scheduled to undergo an endoscopy because of medical indication.
- The subject must have personally signed and dated the patient informed consent form indicating that he/she has been informed of all pertinent aspects of the study.
- The subject must be willing and able to comply with all study procedures.
Who cannot join
- The subject who is unable to undergo gastroscopy.
- The subject with previous total or partial gastrectomy.
- The subject has other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may interfere with the interpretation of study results and in the judgment of the investigator would make the subject unsuitable for entry into the study.
- The subject is unwilling or unable to provide signed informed consent.
- The subject who is pregnant.
Trial locations and contacts
2 sites in 1 country.
Singapore2 sites
National University Hospital, Singapore
Singapore, 119074
Tan Tock Seng Hospital, Singapore
Singapore, 308433
About this study
This study aims to develop a cost-effective screening strategy for the Singapore population by targeted screening of people who have a high risk of stomach cancer, in order to detect early signs of the disease at a stage that can be prevented or cured. Often, patients only consult their doctors when they have advanced symptoms, by which time the cancer may be at a difficult to treat, or incurable stage.
Using costs in the Singapore health system as well as local population risk profiles and demographics, our previous study demonstrated that screening of high-risk groups is cost-effective and a panel of serum makers was effective in differentiating high-risk from low-risk individuals. This study aims to validate the predictive value of various blood biomarkers, such as that of antibodies against Helicobacter pylori, pepsinogen levels, micro RNAs (miRNAs) and blood-based protein markers in participants who have been scheduled to undergo upper gastrointestinal (GI) endoscopy for clinical reasons. If successful, the marker can be used to stratify population into different risk groups and various screening systems can be provided according to different risk level. This will reduce the number of annual invasive screening examinations required to detect early gastric cancer (GC), thereby rendering it cost-effective to generalize as clinical practice in Singapore.
Read the detailed description
Objectives:
This study aims to
- Validate the predictive value of various blood biomarkers, including the panel of antibodies against H.pylori and pepsinogen levels, micro RNAs (miRNAs) and blood-based protein markers in a prospective cohort study involving 8000 participants who have been referred for upper for predicting gastric cancer risk.
- Record the number of participants who are diagnosed with gastric cancer, including high grade dysplasia, carcinoma in-situ and adenocarcinoma.
- Develop a cost-effective screening strategy based on 1 and 2.
Study Design This is a prospective cohort study involving 8000 subjects who are referred for upper GI endoscopy for standard clinical indications. Blood will be drawn from subjects for blood tests, including antibodies against H. pylori, pepsinogen levels, specific miRNA levels, blood-based protein markers, before undergoing an upper GI endoscopy for clinical reasons. Subjects will be monitored for a period of 10 years via verification with the National Registry of Diseases Office (NRDO) of Singapore. The correlation between the blood test results and findings from the clinical endoscopy or NRDO database verification will be analyzed to determine the predictive value.
Enrolment Patients undergoing upper gastrointestinal endoscopy will be considered for enrolment provided they meet the inclusion and exclusion criteria. 8000 subjects will be enrolled. The Patient Informed Consent Form will be discussed with the patient. If acceptable, the form will be signed by the patient, Principal Investigator and witness if applicable. The subject will be assigned initials and a number in the order in which they were enrolled. Subjects will also be asked to provide information on demographics, family history of gastric cancer, diet, medical history, and lifestyle habits. The data will be captured in a comprehensive database.
Blood Collection 15 mls of blood will be drawn from each subject. Serum, plasma and white blood cells will be extracted.
Analyses
- Sera will be assayed for antibodies against H. pylori, Pepsinogen I and II levels to derive H. pylori status and pepsinogen index. Participants will be classified into 4 groups, A, B, C and D, according to H. pylori status and pepsinogen Index. Group A includes subjects negative for both H. pylori antibodies and pepsinogen atrophic gastritis (PGA). Group B subjects will be negative for PGA and positive for H.pylori antibodies. Group C subjects will be positive for both tests. Finally, Group D subjects will be positive for PGA and negative for H. pylori antibodies. The incidence rate and relative risk of gastric cancer as determined by the findings of subjects' clinical gastroscopies or verification with NRDO will be calculated.
- Total RNA from serum or plasma will be isolated and the expression levels of miRNAs will be determined. The final miRNA expression levels after normalization of both technical and biological variations are analyzed with multiple statistical methods to identify panels of miRNAs with the highest discriminatory power between healthy and disease states. Each participant will be assigned a score based on miRNA expression profile, indicating the possibility of having GC. The result will be compared with endoscope and histology result which is the gold standard for diagnosis of GC. We will compare the performance of our miRNA panel with other serum markers including H. pylori status and pepsinogen levels.
- Levels of 10 blood-based protein markers (determined from systematic review) will be analyzed from sera through ELISAs (enzyme-linked immunosorbent assay). Subsequent statistical multivariate analysis may be applied to generate a biomarker panel with a superior diagnostic performance compared to the conventional blood-based biomarkers for gastric cancer.
Sample Size Calculation In our previous case-control study, 10% of the control group had pepsinogen (PG) determined atrophic gastritis, and the odds ratio (95%CI) for the risk of developing gastric cancer was 4.02 (2.56-6.30) compared with subjects who had no PG atrophic gastritis. A minimum of 47 gastric cancer cases are required to evaluate the PG-H. Pylori panel in the prediction of gastric cancer risk (with odds ratio 3.5) at power of 90% and p-value <0.05. Based on the estimated gastric cancer prevalence rate among NUH patients of the gastroenterology and upper GI surgery clinics of 0.6%, a cohort size of 8000 subjects will be needed.
Statistical Analysis The chi-square test and the t-test will be used to compare the distributions of selected demographic, lifestyle and other risk factors between cases and controls. The logistic regression method will be used to examine the associations between blood markers measured and risk of gastric cancer. Statistical computing will be carried out using the SPSS 19. The statistical significance level is set at two-sided P value of 0.05.
- Conditions
- Stomach Neoplasm
- Being tested
- blood-based biomarkers analyses
- Keywords
- Gastric Cancer
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood-based biomarkers analysesDiagnostic test
Analyses of H. pylori antibodies/pepsinogen levels, micro RNAs (miRNAs) or blood-based protein markers levels in participants' blood samples
| Study group | Role | What they receive |
|---|---|---|
| Blood Biomarkers Analyses | 15 ml of blood sample will be obtained from each study participant, for blood-based biomarkers analyses. Receives: Diagnostic Test: blood-based biomarkers analyses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gastric cancer
Number of patients who develop gastric cancer, including high grade dysplasia, carcinoma in-situ and adenocarcinoma
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2020
- Study start3 Dec 2012
- Primary completion29 May 2016
- Study completion29 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Stomach NeoplasmStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 6,862 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Tan Tock Seng Hospital, MiRXES Pte Ltd
- Responsible party
- Sponsor
- Investigators
- Calvin Jianyi Koh, MBBS, MMed, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04329299
- Sponsor's protocol ID
- 2012/00737
- Status last verified
- Mar 2020
- First submitted
- 30 Mar 2020
- Last updated
- 22 Oct 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Dan YY, So JB, Yeoh KG. Endoscopic screening for gastric cancer. Clin Gastroenterol Hepatol. 2006 Jun;4(6):709-16. doi: 10.1016/j.cgh.2006.03.025.
PubMed 16765306Miki K. Gastric cancer screening by combined assay for serum anti-Helicobacter pylori IgG antibody and serum pepsinogen levels - "ABC method". Proc Jpn Acad Ser B Phys Biol Sci. 2011;87(7):405-14. doi: 10.2183/pjab.87.405.
PubMed 21785258Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011 Jun 7;8(8):467-77. doi: 10.1038/nrclinonc.2011.76.
PubMed 21647195Song JH, Meltzer SJ. MicroRNAs in pathogenesis, diagnosis, and treatment of gastroesophageal cancers. Gastroenterology. 2012 Jul;143(1):35-47.e2. doi: 10.1053/j.gastro.2012.05.003. Epub 2012 May 10.
PubMed 22580099So JBY, Kapoor R, Zhu F, Koh C, Zhou L, Zou R, Tang YC, Goo PCK, Rha SY, Chung HC, Yoong J, Yap CT, Rao J, Chia CK, Tsao S, Shabbir A, Lee J, Lam KP, Hartman M, Yong WP, Too HP, Yeoh KG. Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population. Gut. 2021 May;70(5):829-837. doi: 10.1136/gutjnl-2020-322065. Epub 2020 Oct 7.
PubMed 33028667Bibault JE, Chang DT, Xing L. Development and validation of a model to predict survival in colorectal cancer using a gradient-boosted machine. Gut. 2021 May;70(5):884-889. doi: 10.1136/gutjnl-2020-321799. Epub 2020 Sep 4.
PubMed 32887732
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Blood Biomarkers to Predict Gastric Cancer Risk
- ClinicalTrials.gov ID
- NCT04329299
- Acronym / sponsor ID
- 2012/00737
- Conditions
- Stomach Neoplasm
- Keywords
- Gastric Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6,862 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- Tan Tock Seng Hospital, MiRXES Pte Ltd
- Study start
- 3 Dec 2012 (actual)
- Primary completion
- 29 May 2016 (actual)
- Study completion
- 29 May 2016 (actual)
- First posted
- 1 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to develop a cost-effective screening strategy for the Singapore population by targeted screening of people who have a high risk of stomach cancer, in order to detect early signs of the disease at a stage that can be prevented or cured. Often, patients only consult their doctors when they have advanced symptoms, by which time the cancer may be at a difficult to treat, or incurable stage.
Using costs in the Singapore health system as well as local population risk profiles and demographics, our previous study demonstrated that screening of high-risk groups is cost-effective and a panel of serum makers was effective in differentiating high-risk from low-risk individuals. This study aims to validate the predictive value of various blood biomarkers, such as that of antibodies against Helicobacter pylori, pepsinogen levels, micro RNAs (miRNAs) and blood-based protein markers in participants who have been scheduled to undergo upper gastrointestinal (GI) endoscopy for clinical reasons. If successful, the marker can be used to stratify population into different risk groups and various screening systems can be provided according to different risk level. This will reduce the number of annual invasive screening examinations required to detect early gastric cancer (GC), thereby rendering it cost-effective to generalize as clinical practice in Singapore.
Detailed description
Objectives:
This study aims to
- Validate the predictive value of various blood biomarkers, including the panel of antibodies against H.pylori and pepsinogen levels, micro RNAs (miRNAs) and blood-based protein markers in a prospective cohort study involving 8000 participants who have been referred for upper for predicting gastric cancer risk.
- Record the number of participants who are diagnosed with gastric cancer, including high grade dysplasia, carcinoma in-situ and adenocarcinoma.
- Develop a cost-effective screening strategy based on 1 and 2.
Study Design This is a prospective cohort study involving 8000 subjects who are referred for upper GI endoscopy for standard clinical indications. Blood will be drawn from subjects for blood tests, including antibodies against H. pylori, pepsinogen levels, specific miRNA levels, blood-based protein markers, before undergoing an upper GI endoscopy for clinical reasons. Subjects will be monitored for a period of 10 years via verification with the National Registry of Diseases Office (NRDO) of Singapore. The correlation between the blood test results and findings from the clinical endoscopy or NRDO database verification will be analyzed to determine the predictive value.
Enrolment Patients undergoing upper gastrointestinal endoscopy will be considered for enrolment provided they meet the inclusion and exclusion criteria. 8000 subjects will be enrolled. The Patient Informed Consent Form will be discussed with the patient. If acceptable, the form will be signed by the patient, Principal Investigator and witness if applicable. The subject will be assigned initials and a number in the order in which they were enrolled. Subjects will also be asked to provide information on demographics, family history of gastric cancer, diet, medical history, and lifestyle habits. The data will be captured in a comprehensive database.
Blood Collection 15 mls of blood will be drawn from each subject. Serum, plasma and white blood cells will be extracted.
Analyses
- Sera will be assayed for antibodies against H. pylori, Pepsinogen I and II levels to derive H. pylori status and pepsinogen index. Participants will be classified into 4 groups, A, B, C and D, according to H. pylori status and pepsinogen Index. Group A includes subjects negative for both H. pylori antibodies and pepsinogen atrophic gastritis (PGA). Group B subjects will be negative for PGA and positive for H.pylori antibodies. Group C subjects will be positive for both tests. Finally, Group D subjects will be positive for PGA and negative for H. pylori antibodies. The incidence rate and relative risk of gastric cancer as determined by the findings of subjects' clinical gastroscopies or verification with NRDO will be calculated.
- Total RNA from serum or plasma will be isolated and the expression levels of miRNAs will be determined. The final miRNA expression levels after normalization of both technical and biological variations are analyzed with multiple statistical methods to identify panels of miRNAs with the highest discriminatory power between healthy and disease states. Each participant will be assigned a score based on miRNA expression profile, indicating the possibility of having GC. The result will be compared with endoscope and histology result which is the gold standard for diagnosis of GC. We will compare the performance of our miRNA panel with other serum markers including H. pylori status and pepsinogen levels.
- Levels of 10 blood-based protein markers (determined from systematic review) will be analyzed from sera through ELISAs (enzyme-linked immunosorbent assay). Subsequent statistical multivariate analysis may be applied to generate a biomarker panel with a superior diagnostic performance compared to the conventional blood-based biomarkers for gastric cancer.
Sample Size Calculation In our previous case-control study, 10% of the control group had pepsinogen (PG) determined atrophic gastritis, and the odds ratio (95%CI) for the risk of developing gastric cancer was 4.02 (2.56-6.30) compared with subjects who had no PG atrophic gastritis. A minimum of 47 gastric cancer cases are required to evaluate the PG-H. Pylori panel in the prediction of gastric cancer risk (with odds ratio 3.5) at power of 90% and p-value <0.05. Based on the estimated gastric cancer prevalence rate among NUH patients of the gastroenterology and upper GI surgery clinics of 0.6%, a cohort size of 8000 subjects will be needed.
Statistical Analysis The chi-square test and the t-test will be used to compare the distributions of selected demographic, lifestyle and other risk factors between cases and controls. The logistic regression method will be used to examine the associations between blood markers measured and risk of gastric cancer. Statistical computing will be carried out using the SPSS 19. The statistical significance level is set at two-sided P value of 0.05.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blood Biomarkers Analyses | – | Diagnostic Test: blood-based biomarkers analyses15 ml of blood sample will be obtained from each study participant, for blood-based biomarkers analyses. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who have been referred to the participating study sites for upper GI endoscopy for standard clinical indications.
Key inclusion criteria (4 listed)
- The subject is greater than 40 years of age.
- The subject is scheduled to undergo an endoscopy because of medical indication.
- The subject must have personally signed and dated the patient informed consent form indicating that he/she has been informed of all pertinent aspects of the study.
- The subject must be willing and able to comply with all study procedures.
Key exclusion criteria (5 listed)
- The subject who is unable to undergo gastroscopy.
- The subject with previous total or partial gastrectomy.
- The subject has other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may interfere with the interpretation of study results and in the judgment of the investigator would make the subject unsuitable for entry into the study.
- The subject is unwilling or unable to provide signed informed consent.
- The subject who is pregnant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood-based biomarkers analysesAnalyses of H. pylori antibodies/pepsinogen levels, micro RNAs (miRNAs) or blood-based protein markers levels in participants' blood samples | Diagnostic test | Blood Biomarkers Analyses |
Primary outcome
Gastric cancer
Time frame: 10 years
Number of patients who develop gastric cancer, including high grade dysplasia, carcinoma in-situ and adenocarcinoma
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Background: PubMed 16765306Dan YY, So JB, Yeoh KG. Endoscopic screening for gastric cancer. Clin Gastroenterol Hepatol. 2006 Jun;4(6):709-16. doi: 10.1016/j.cgh.2006.03.025.
- Background: PubMed 21785258Miki K. Gastric cancer screening by combined assay for serum anti-Helicobacter pylori IgG antibody and serum pepsinogen levels - "ABC method". Proc Jpn Acad Ser B Phys Biol Sci. 2011;87(7):405-14. doi: 10.2183/pjab.87.405.
- Background: PubMed 21647195Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011 Jun 7;8(8):467-77. doi: 10.1038/nrclinonc.2011.76.
- Background: PubMed 22580099Song JH, Meltzer SJ. MicroRNAs in pathogenesis, diagnosis, and treatment of gastroesophageal cancers. Gastroenterology. 2012 Jul;143(1):35-47.e2. doi: 10.1053/j.gastro.2012.05.003. Epub 2012 May 10.
- Derived from this study: PubMed 33028667So JBY, Kapoor R, Zhu F, Koh C, Zhou L, Zou R, Tang YC, Goo PCK, Rha SY, Chung HC, Yoong J, Yap CT, Rao J, Chia CK, Tsao S, Shabbir A, Lee J, Lam KP, Hartman M, Yong WP, Too HP, Yeoh KG. Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population. Gut. 2021 May;70(5):829-837. doi: 10.1136/gutjnl-2020-322065. Epub 2020 Oct 7.
- Derived from this study: PubMed 32887732Bibault JE, Chang DT, Xing L. Development and validation of a model to predict survival in colorectal cancer using a gradient-boosted machine. Gut. 2021 May;70(5):884-889. doi: 10.1136/gutjnl-2020-321799. Epub 2020 Sep 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Calvin Jianyi Koh, MBBS, MMed principal investigator
National University Hospital, Singapore
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Stomach Neoplasm, run by National University Hospital, Singapore at 2 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gastric cancer (time frame: 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04329299, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.