A Research of Berberine Hydrochloride to Prevent Colorectal Adenomas in Patients With Previous Colorectal Cancer

Study Overview
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Brief Summary
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Experimental studies in animals and observational studies in humans suggest that fusobacterium nucleatum is associates with stages of colorectal neoplasia development, and Berberine Hydrochloride could rescue Fusobacterium nucleatum-induced colorectal tumorigenesis by modulating the tumor microenvironment. Whether regular Berberine Hydrochloride use may decrease the risk of colorectal adenomas, the precursors to most colorectal cancers is worth to further study.

Detailed Description
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The prevalence of colorectal adenomas is high in our country, as is the incidence of colorectal cancer. It is well-known that colorectal adenomas are the precursor of colorectal cancer and that removing them will prevent colorectal cancer. Because most colorectal cancers arise from benign adenomas, adenomas have been used as surrogate end points in prevention trials. Berberine hydrochloride, which is an alkaloid extracted from Rhizoma coptidis, has been traditionally used in Chinese medicine to treat gastrointestinal infections, due to its antimicrobial properties. Previous clinical research and animal studies have demonstrated the anti-tumor action of Berberine hydrochloride. Persons with a history of colorectal cancer might constitute a group at higher risk for adenomas and thus be particularly suitable for a study of the chemopreventive effects of Berberine hydrochloride. Here, a randomized, double-blind, placebo-controlled trial was designed to determine whether the daily use of 300 mg of berberine hydrochloride could decreases the occurrence of new colorectal adenomas among patients with a history of colorectal cancer.

Official Title
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A Randomized Trial of Berberine Hydrochloride to Prevent Colorectal Adenomas in Patients With Previous Colorectal Cancer

Conditions
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Colorectal Adenomas

Intervention / Treatment
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* Drug: Berberine hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18-80 years Patients who had histologically documented colon or rectal cancer with a low risk of recurrent disease Patients with Dukes' stage A or B1 colon or rectal cancer (tumor-node-metastasis [TNM] stage T1 to T2, N0, M0) who had undergone curative resection of the primary tumor were immediately eligible for enrollment Patients with Dukes' stage B2 or C (T3 to T4, N0 to N1, M0) colon or rectal cancer who had undergone curative resection of the primary tumor were eligible if they had been free of disease for more than five years after curative surgery Eligible participants had to have undergone, after adequate preparation, colonoscopy to the cecum (or small-bowel anastomosis), with removal of all polyps, within four months before study entry Patients were eligible if they were in good general health, with an expected survival of at least five years; willing to provide and able to understand informed consent and to cooperate with the study procedures; not currently enrolled in a clinical trial of colon-cancer treatment or other chemoprevention trial; and not pregnant or nursing. Exclusion Criteria: Patients who are hypersensitive or intolerant to the drugs Patients had familial polyposis Patients had invasive cancer other than nonmelanoma skin cancer within 5 years before the intake appointment Patients with diabetes mellitus, severe renal disease or cardiovascular disease (defined by a New York Heart Association functional classof III or IV) Patients with hypercalcemia or urolithiasis Patients had a history of inflammatory bowel disease Patients with hemolytic anemia and glucose -6- phosphate dehydrogenase deficiency Patients had received immunosuppressive therapy within the previous 6 months Patients had clinically obvious narcotic or alcohol dependence during the previous 6 months Patients had used NSAIDs including aspirin at any dose on 3 or more days per month during each of the 3 months before enrollment or for a period of 36 days in the previous year; or had a history of stroke, transient ischemic attacks, angina, myocardial infarction, or atherosclerotic peripheral vascular disease Pregnant women, women during breast-feeding period, or women with expect pregnancy Patients with a history of subtotal gastrectomy or partial bowel resection Patients who are not able to cooperate Patients with any condition that could be worsened by supplemental Berberine hydrochloride

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Berberine hydrochloride group<br>Berberine hydrochloride 300mg tablet by mouth, two times per day for 3 years | Drug: Berberine hydrochloride<br>* patients take the Berberine hydrochloride 300mg tablet by mouth, 2 times a day with 3 years.<br>* Other names: Berberine hydrochloride tablet (Sine Tianping);|
| Placebo Comparator: Placebo<br>identical-appearing placebo 300mg tablet by mouth, two times per day for 3 years | Drug: Placebo<br>* pill manufactured to mmic Berberine hydrochloride 100mg tablet<br>* Other names: Placebo (for Berberine hydrochloride);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative the colorectal adenoma incidence rate during Berberine hydrochloride or placebo treatment in patients with a history of colorectal cancer | The proportion of patients in whom one or more colorectal adenomas were investigated during the period from one year after randomization through the anticipated surveillance follow-up examination. The development of colorectal adenomas was assessed with an Olympus flexible video colonoscopy. One endoscopic investigator, who did not review the records of previous examinations, made all the assessments. | From baseline to 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative the numbers or diameters of those new colorectal adenomas during Berberine hydrochloride or placebo treatment in patients with a history of colorectal cancer | The numbers or diameters of those new colorectal adenomas were analyzed during the period from one year after randomization through the anticipated surveillance follow-up examination. The endoscopic investigator, who did not review the records of previous examinations, counted the total number of colorectal adenomas, and the examination was recorded on videotape. The diameter of those colorectal adenomas was measured in millimeters with a graduated scale passed through the colonoscopy biopsy channel. | From baseline to 3 years. |