Clinical trial NCT04638959: Study of Faecal Bacteria Detection in Early Screening and Diagnosis of GC
Official title: Faecal Bacteria Detection in Early Screening and Diagnosis of Gastric Cancer: a Large-scale Multi-center Case-control Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Non-invasive and Sensitive Faecal Bacterial Markers for Early Screening and Diagnosis of Gastric Cancer
Keywords: faecal bacterial marker
early screening and diagnosis
gastric cancer
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai Changzheng Hospital
name: Ruijin Hospital
name: Jing'an District Central Hospital of Shanghai
name: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
name: Nanfang Hospital, Southern Medical University
name: Seventh Medical Center of PLA Army General Hospital
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Zhongshan Hospital Xiamen University
name: Tianjin Medical University General Hospital
First posted: 2020-11-20
Enrollment: 1100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants are required to complete a structured questionnaire for assessment of inclusion requirement.

Brief summary: In this clinical trial, we aim to explore the synergistic alteration of specific bacteria both in gastric mucosas and feces of gastric cancer patients for the method of non-invasive and cost-effective faecal marker detection. We aim to select and validate specific microbes as noninvasive, accurate, simple, sensitive and highly-accepted biomarkers that might assist to screen and diagnose gastric cancer, especially early gastric cancer patients.

Detailed description: We conducted a large-scale multi-centre retrospective case-control study. Approximately a total of 1080 volunteers aging 40-75 in three independent cohorts, discovery cohort, validation cohort 1, validation cohort 2, will be recruited from 10 hospitals throughout China. Among them, 530 subjects in both discovery cohort and validation cohort 1 were from Shanghai Jiao Tong University School of Medicine Renji Hospital from August to December in 2018. Around 550 participants will be enrolled in validation cohort 2 from nine hospitals in China.Each cohort recruits both patients diagnosed with GC (GC group) and gender, age and body mass index (BMI)-matched healthy-control (HC) individuals diagnosed with chronic gastritis by histopathology). Individuals enrolled were either asymptomatic undergoing upper GI endoscopy screening or went to GI clinic with digestive symptoms. Subjects in HC group are conducted colonoscopy within 0.5 year before or after upper endoscopy. We collect gastric tissue biopsies and stool samples from gastric cancer patients and healthy-controls. First in the discovery cohort, which will recruit 20 subjects, 13 pairs of both cancerous \& noncancerous gastric tissues and pre-operation feces in GC group will be collected. 7 subjects provide their paired mucosal biopsies and stools in HC group before examination. 16S ribosomal RNA gene sequencing will be used to select the synergistically differential bacteria species as well as find out microbial compositional distinction and diversity from both tissue and stool samples between GC and HC group. Second, the validation cohort 1 recruiting a total of 510 subjects (294 GC patients and 216 HC individuals), 217 pre-operation faecal specimens and 141 fresh tissues (cancerous \& noncancerous tissues) from GC group, and 127 faecal samples and 124 gastric biopsies will be collected. Quantitative PCR (qPCR) will be used to validate the high-throughput sequencing results in discovery cohort in a single center. Among them, 35 objects in HC group and 64 patients in GC group will provide their paired tissues and feces. Third, in validation cohort 2, we are going to enroll volunteers from multiple geographic locations to confirm our results. 550 stool samples will be collected to further validate the accuracy, sensitivity and specificity of the cut-off value analyzed from validation cohort 1. All results of laboratory tests including tumor markers CEA, CA199,CA724 were obtained from the electronic query system. The GC stages will be assessed by the TNM system according to AJCC Version 4.2017 based on surgical records, histopathology and radiographic images (eg. PET-CT, abdominal enhanced CT). All subjects will sign up informed consent form before sample collection. The protocol of present study was approved by Ethics Review Committee of all participating hospitals.

Eligibility criteria: Inclusion Criteria:

* 1）Age between 40 and 75;
* 2）Subjects in GC group are pathologically diagnosed as gastric cancer prior to any treatment such as surgery, endoscopic resection, chemotherapy, radiotherapy, immunotherapy, traditional Chinese medicine therapy, etc. The results of their preoperative abdominal enhanced CT or PET-CT indicated no obvious bowel abnormalities (inflammation, polyps, ulcers, tumors, erosions, melanosis, etc.);
* 3) Subjects in HC group are diagnosed with chronic gastritis by endoscopy and pathology. without ulcers, polyps, tumors, severe erosions or bile reflux, and no obvious abnormal findings (inflammation, polyps, ulcers, tumors, erosions, melanosis, etc.) by colonoscopy within half a year;
* 4) Subjects are willing to cooperate with this research and provide stool/mucosa samples as required.

Exclusion Criteria:

* 1) with severe systemic infection, nasopharyngeal/oral cavity inflammation (periodontitis, gingivitis, tonsillitis, etc.), respiratory tract infection, soft tissue or skin infection, abscess or endocarditis within 3 months prior to recruitment;
* 2）prior medication history of the following medicine within 3 months: nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressor, antibiotics, probiotics, hormones or immune-suppressants at least 1 week;
* 3）prior medication history of proton-pump inhibitors or H2 receptor inhibitors for over 2 months within 1 year;
* 4) with a history of H.pylori eradication therapy within 1 year;
* 5) with severe constipation, diarrhea or defecation habits changes within 3 months;
* 6) personal history of cancer, organ transplantation, parasites infection or other severe digestive system diseases (inflammatory bowel disease, liver cirrhosis, etc.);
* 7) with uncontrolled digestive bleeding, obstruction, perforation and any trauma or surgery within 3 months;
* 8) with uncontrolled chronic metabolic or endocrine disorders, e.g. hypertension, diabetes, hyperlipidemia, hyperuricemia, etc.
* 9) on a vegetarian diet or with great changes of eating habits within 3 months;
* 10) refusal of participate in this study.

Primary outcomes:
measure: differences in abundance of gut microbiota
timeFrame: 1 year
Secondary outcomes:
measure: evidence of gastric carcinoma
timeFrame: 1 year
Other outcomes:
measure: Basic information of patients with different clinical outcomes
timeFrame: 1 year
Locations:
city: Beijing
country: China
facility: Department of Gastroenterology, the Seventh Medical Center of PLA General Hospital
state: Beijing
city: Xiamen
country: China
facility: Department of Gastroenterology, Zhongshan Hospital, Xiamen University
state: Fujian
city: Guangdong
country: China
facility: Department of Gastroenterology, Nanfang Hospital, Southern Medical Univerisity
state: Guangzhou
city: Nanjing
country: China
facility: Division of Gastroenterology and Hepatology, The Affiliated DrumTower of Nanjing University Medical School
state: Jiangsu
city: Shanghai
country: China
facility: Division of Gastroenterology and Hepatology, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health
state: Shanghai
city: Tianjin
country: China
facility: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University
state: Tianjin
city: Shanghai
country: China
facility: Jing'an District Central Hospital of Shanghai
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital
Study officials:
References:
citation: Zhou CB, Pan SY, Jin P, Deng JW, Xue JH, Ma XY, Xie YH, Cao H, Liu Q, Xie WF, Zou XP, Sheng JQ, Wang BM, Wang H, Ren JL, Liu SD, Sun YW, Meng XJ, Zhao G, Chen JX, Cui Y, Wang PQ, Guo HM, Yang L, Chen X, Ding J, Yang XN, Wang XK, Qian AH, Hou LD, Wang Z, Chen YX, Fang JY. Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer. Gastroenterology. 2022 Jun;162(7):1933-1947.e18. doi: 10.1053/j.gastro.2022.02.015. Epub 2022 Feb 12.