Colorectal Adenomas, Colorectal Cancers
Conditions
Keywords
colorectal adenomas, colorectal cancers, Berberine hydrochloride, human gut microbiome
Brief summary
Berberine hydrochloride is a conventional component in Chinese medicine. In recent years, anticancer activity of berberine hydrochloride have been explored. The aim of this study is to investigate the effect of berberine hydrochloride on the human gut microbiome.
Interventions
Oral Administration of Berberine Hydrochloride
Sponsors
Jing-yuan Fang, MD, Ph. D
Shanghai Jiao Tong University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Outpatients undergoing colonoscopy at Renji Hospital who meet the following criteria: 1. Aged 18-75 years; 2. Had at least one but no more than six histologically confirmed colorectal adenomas (including tubular, tubulovillous, and villous adenomas) removed within 6 months prior to enrollment; 3. Provide informed consent for this study and are able to comply with the requirements for collecting qualified stool specimens, peripheral blood specimens, and providing relevant lifestyle and medical history information. Healthy subjects who meet the following criteria: 1. Aged 18-75 years; 2. Have undergone colonoscopy within 6 months prior to enrollment with no histologically confirmed colorectal adenomas (including tubular, tubulovillous, and villous adenomas); 3. Provide informed consent for this study and are able to comply with the requirements for collecting qualified stool specimens, peripheral blood specimens, and providing relevant lifestyle and medical history information.
Exclusion criteria
The following outpatients undergoing colonoscopy at Renji Hospital: 1. Incomplete resection of adenoma during colonoscopy; 2. Individuals at high risk for hereditary colorectal cancer; 3. Regular use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, calcium, or vitamin D (defined as daily intake of ≥100 mg aspirin and ≥1200 mg calcium for at least 3 months); 4. History of subtotal gastrectomy, total gastrectomy, or partial enterectomy; 5. History of severe cardiac, hepatic, renal disease, or cancer; 6. Severe constipation or psychiatric disorders; 7. Pregnant, breastfeeding, or planning to become pregnant; 8. Undergone colonoscopy with inadequate bowel preparation (rated as "poor" or "insufficient" according to the Aronchik scale) or short observation time (withdrawal time \<6 minutes). 9. Use of antibiotics, probiotics, or prebiotics within 1 month prior to enrollment. The following healthy subjects: 1. Individuals at high risk for hereditary colorectal cancer; 2. Regular use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, calcium, or vitamin D (defined as daily intake of ≥100 mg aspirin and ≥1200 mg calcium for at least 3 months); 3. History of subtotal gastrectomy, total gastrectomy, or partial enterectomy; 4. History of severe cardiac, hepatic, renal disease, or cancer; 5. Severe constipation or psychiatric disorders; 6. Pregnant, breastfeeding, or planning to become pregnant; 7. Undergone colonoscopy with inadequate bowel preparation (rated as "poor" or "insufficient" according to the Aronchik scale) or short observation time (withdrawal time \<6 minutes). 8. Use of antibiotics, probiotics, or prebiotics within 1 month prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative abundance of Akkermansia in fecal samples as measured by quantitative PCR (qPCR) | 2 weeks | Fecal samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. The relative abundance of Akkermansia will be quantified using quantitative PCR (qPCR) targeting species-specific 16S rRNA gene sequences. Results will be expressed as the relative abundance normalized to total bacterial load (ΔCt method). Changes from baseline to post-treatment will be calculated for each participant and summarized across the study population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with abnormal liver and renal function laboratory values | 2 weeks | Blood samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. Liver function will be assessed by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and albumin. Renal function will be evaluated using serum creatinine (Cr) and blood urea nitrogen (BUN). Abnormal laboratory values will be defined according to institutional reference ranges. The number and proportion of participants with abnormal values after treatment will be reported. Changes from baseline for each parameter will also be summarized descriptively. |
| Relative abundance and diversity of gut microbiota in fecal samples as assessed by 16S rRNA gene sequencing | 2 weeks | Fecal samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. Gut microbiota composition will be analyzed using 16S rRNA gene sequencing. Outcomes will include: 1. relative abundance of bacterial taxa at the phylum and genus levels (excluding Akkermansia where applicable), and 2. alpha diversity indices (Shannon index). Changes from baseline to post-treatment will be calculated for each participant and summarized across the study population. |
| Plasma concentration of indole-3-pyruvic acid (IPyA) as measured before and after berberine hydrochloride administration | 2 weeks | Peripheral blood samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. The concentration of indole-3-pyruvic acid (IPyA) in plasma will be quantified using a validated analytical method (liquid chromatography-mass spectrometry, LC-MS). Changes in IPyA concentration from baseline to post-administration will be calculated for each participant and summarized across the study population. |
| Fecal concentration of indole-3-pyruvic acid (IPyA) as measured before and after berberine hydrochloride administration | 2 weeks | Fecal samples will be collected at baseline (prior to berberine hydrochloride administration) and after treatment. The concentration of indole-3-pyruvic acid (IPyA) in fecal samples will be quantified using a validated analytical method (liquid chromatography-mass spectrometry, LC-MS). Changes in IPyA concentration from baseline to post-administration will be calculated for each participant and summarized across the study population. |
| Proportion of VEGFA-positive cells in adenoma tissue as assessed by immunohistochemistry | Baseline and at follow-up colonoscopy (approximately 6 months [±2 months] after treatment) | Adenoma tissue samples will be obtained at the time of endoscopic resection for patients with colorectal adenomas, before and after administration of hydrochloride berberine. Immunohistochemical staining will be performed to detect vascular endothelial growth factor A (VEGFA) expression. The proportion of VEGFA-positive cells will be quantified by calculating the percentage of positively stained cells among total cells in representative high-power fields. Results will be summarized descriptively across participants. If applicable, comparisons with baseline or between subgroups may be explored. |
Contacts
CONTACTZiran Kang, M.D.
PRINCIPAL_INVESTIGATORJingyuan Fang, M.D.
Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Outcome results
None listed