Research on the Physiological Characteristics of the Gastrointestinal Tract in Chinese Volunteers

The dissolution and absorption of oral drugs in the gastrointestinal tract is a complex process, which is affected by physiological factors such as transporters, metabolic enzymes, gene phenotypes, gastrointestinal diseases, intestinal flora and so on. Therefore, the investigators are planning to collect gastrointestinal mucosa tissues, gastric juice, saliva , feces and blood samples to investigate (1) the activity and abundance of metabolism enzymes/transports in different section of gastrointestinal tract, (2) the composition and physicochemical properties of gastric juice; (3) the distribution and abundance of bacterial in gastrointestinal mucosa, saliva, gastric juice and feces; (4) the composition and content of bile acid in gastrointestinal mucosa, gastric juice and plasma in Chinese volunteers who planning to undergo digestive endoscopy.

Study Overview

• Status: Active, not recruiting
• Conditions: Endoscopy, Gastrointestinal

Detailed Description

This is a single-center, open-labelled study. Twenty four Chinese adult volunteers who schedule for gastrointestinal endoscopy will be enrolled and will be not allowed to take products containing grapefruit, fruit juice, tea, coffee, wine and other foods or drinks containing caffeine, xanthine and alcohols at least 14 days before the gastrointestinal endoscopes. In addition, smoking is also prohibited. Screen will be performed any day between 3 and 14 days prior to the gastrointestinal endoscopes. Feces, saliva and 4 ml whole blood samples will be collected from these participants 3 days before gastrointestinal endoscopes for the detection of bacterial diversity, metabolic enzymes, transporter-related genotypes and bile acids. Afterwards, participants will undergo painless gastroscopy. Meanwhile, gastric juice, mucosal tissue from stomach, duodenum, jejunum, ileum, colon will be collected. The total number of mucosal tissue no more than 10.

• Study Type: Observational
• Enrollment (Anticipated): 24

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Dongyang Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Chinese volunteers who are planning to undergo gastrointestinal endoscopy

Description

Inclusion Criteria:

1. Chinese volunteers who are planning to undergo digestive endoscopy;
2. Volunteers who have a full understanding of the content, process and possible adverse reactions of the study and have signed an informed consent form before the clinical trial;
3. Volunteers who are able to complete the clinical trial according to the protocol;
4. Male and female volunteers between the ages of 18 and 60 (including both ends) on the date of signing the consent form;
5. Female volunteers are non-pregnant or non-lactating women, and will live asexually after enrollment until the end of the trial;
6. Male volunteers weigh no less than 50 kg, female volunteers weigh no less than 45 kg, and the body mass index (BMI) of male and female volunteers within the range of 19.0-26.0 kg/m2 (including cut-off values);
7. The comprehensive physical examination, routine laboratory examinations are normal or abnormal, but the investigator judges that there is no clinical significance;
8. Volunteers who are able to abstain from alcohol, coffee, non-prescription drugs or prescription drugs, and no food and beverages related to grapefruit within 14 days before the start of the test until the end of the test;
9. Volunteers have no history of smoking

Exclusion Criteria:

1. Volunteers who disagree with "No food or beverages containing caffeine, xanthine and alcohols such as grapefruit-containing products, juice, tea, coffee, wine, etc., 14 days before endoscope", "No smoking 14 days before endoscope";
2. Volunteers who do not comply with the relevant regulations about endoscope;
3. Volunteers with endoscope contraindications;
4. Volunteers with HCV, HIV, HBsAg and/or syphilis positive antibody;
5. Volunteers with allergic physique;
6. Volunteers with needlesickness, blood phobia, difficult in collecting blood and in tolerating local anesthesia;
7. Females who are pregnant, breastfeeding, or taking birth control pills for less than 3 months;
8. Volunteers have bleeding disorders, or therapeutic anticoagulation (warfarin, aspirin, clopidogrel, traditional Chinese medicine, etc.), or anesthesia dependence or alcohol dependence;
9. Volunteers have the smoking history, alcoholism history, alcohol screening positive, drug screening positive, history of drug abuse in the past five years or administration drugs in the three months prior to the trial;
10. Alcoholics (14 units of alcohol consumed per week: 1 unit = 285 mL beer, or 25 mL spirits, or 100 mL wine) and volunteers who cannot prohibition from the time of enrollment to the end of the study;
11. Volunteers who have a history of gastrointestinal disease with a definite severity or have diseases that have been considered unsuitable for participating in this study by researchers;
12. Volunteers with obvious gastrointestinal discomfort within 6 months before the start of the clinical trial;
13. Volunteers who have undergone gastrointestinal and liver surgery and those who have received any other surgery 6 months before the clinical trial;
14. The clinical laboratory examination is abnormal and the researchers judges that it has clinical significance;
15. Volunteers who have taken any clinical trial drugs within 3 months;
16. Volunteers who have used any antibiotics within 3 months;
17. Volunteers who have used any drug within 1 month;
18. Volunteers with hypertension （systolic blood pressure>139 mmHg，diastolic blood pressure>89 mmHg);
19. Volunteers with Parkinson's disease or family history of Parkinson's disease;
20. Volunteers with a family history of sudden cardiac death or arrhythmia;
21. Habitual drink, including coffee, tea, grapefruit juice and so on;
22. Significant weight loss recently;
23. Researcher judge that the volunteer has other factors that are not suitable for participating in this study, regardless of their severity

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Endoscopy; Chinese volunteers who are scheduling for gastro-colonoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The activity and abundance of metabolism enzymes/transports in different section of gastrointestinal tract	LC-MS / MS will be used to quantitatively determine the activity of enzymes/transporters and protein content in mucosal samples including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP3A4, CYP3A5, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A10, UGT2B7, UGT2B17, ABCB1, ABCC2, ABCC3, ABCG2, ASBT, CNT1, CNT2, SGLT1, OATP2B1, OCTN1, OCIN2, OCT1, OCT3, PEPT1.	Feb,2021-Sep, 2022
The physicochemical properties of gastric juice	The physicochemical properties of gastric juice including pH, viscosity, buffer capacity, osmotic pressure, and so on will be determined by means of pH-meter, rheometer, burette, freezing point depression, and so on	Feb,2021-Sep, 2022
The composition of gastric juice	The composition of protein in gastric juice will be measured by LC-MS/MS or HPLC	Feb,2021-Sep, 2022
The composition and content of bile acid in gastrointestinal mucosa, gastric juice and plasma	LC-MS/MS or HPLC will be used to determine the composition of bile acids in mucosal tissues, gastric juice and blood	Feb,2021-Sep, 2022
The distribution of bacterial in gastrointestinal mucosa, saliva, gastric juice and feces	The distribution of bacteria in mucosa samples and gastric juice will be determined by high-throughput sequencing	Feb,2021-Sep, 2022
The abundance of bacterial in gastrointestinal mucosa, saliva, gastric juice and feces	The abundance of bacteria in mucosa samples and gastric juice will be determined by high-throughput sequencing	Feb,2021-Sep, 2022

Collaborators and Investigators

• Sponsor: Dongyang Liu

Publications and helpful links

General Publications

• Van Den Abeele J, Rubbens J, Brouwers J, Augustijns P. The dynamic gastric environment and its impact on drug and formulation behaviour. Eur J Pharm Sci. 2017 Jan 1;96:207-231. doi: 10.1016/j.ejps.2016.08.060. Epub 2016 Sep 3.
• Hayashi M, Matsumoto N, Takenoshita-Nakaya S, Takeba Y, Watanabe M, Kumai T, Takagi M, Tanaka M, Otsubo T, Kobayashi S. Individual metabolic capacity evaluation of cytochrome P450 2C19 by protein and activity in the small intestinal mucosa of Japanese pancreatoduodenectomy patients. Biol Pharm Bull. 2011;34(1):71-6. doi: 10.1248/bpb.34.71.
• Berggren S, Gall C, Wollnitz N, Ekelund M, Karlbom U, Hoogstraate J, Schrenk D, Lennernas H. Gene and protein expression of P-glycoprotein, MRP1, MRP2, and CYP3A4 in the small and large human intestine. Mol Pharm. 2007 Mar-Apr;4(2):252-7. doi: 10.1021/mp0600687. Epub 2007 Jan 31.
• Kalantzi L, Goumas K, Kalioras V, Abrahamsson B, Dressman JB, Reppas C. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm Res. 2006 Jan;23(1):165-76. doi: 10.1007/s11095-005-8476-1. Epub 2006 Dec 1.
• Perez de la Cruz Moreno M, Oth M, Deferme S, Lammert F, Tack J, Dressman J, Augustijns P. Characterization of fasted-state human intestinal fluids collected from duodenum and jejunum. J Pharm Pharmacol. 2006 Aug;58(8):1079-89. doi: 10.1211/jpp.58.8.0009.
• Vasapolli R, Schutte K, Schulz C, Vital M, Schomburg D, Pieper DH, Vilchez-Vargas R, Malfertheiner P. Analysis of Transcriptionally Active Bacteria Throughout the Gastrointestinal Tract of Healthy Individuals. Gastroenterology. 2019 Oct;157(4):1081-1092.e3. doi: 10.1053/j.gastro.2019.05.068. Epub 2019 Jun 5.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2020
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: January 27, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 8, 2021

Study Record Updates

• Last Update Posted (Actual): February 8, 2021
• Last Update Submitted That Met QC Criteria: February 4, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: CPPO-PKMS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No