Primary Chemoprevention of Familial Adenomatous Polyposis With Berberine Hydrochloride
Primary Purpose
Colorectal Adenomas
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
100mg Berberine hydrochloride
300mg Berberine hydrochloride
Placebo Oral Tablet
Sponsored by
About this trial
This is an interventional prevention trial for Colorectal Adenomas
Eligibility Criteria
Inclusion Criteria:
- Patients aged 18-65 years
- Patients with familial adenomatous polyposis, who had not had their entire colorectum removed, and who had five or more polyps 2 mm or more in diameter that could be assessed endoscopically
- All potential subjects received genetic counseling before undergoing genetic testing for APC gene mutations.
- Eligible subjects had a disease-causing mutation of the APC gene but had no endoscopically detectable colorectal adenomatous polyps and no history of colonic surgery
Exclusion Criteria:
- Patients who are hypersensitive or intolerant to the drugs
- Patients who had a history of colectomy or colectomy anticipated within 8 months after randomization
- Patients with abnormal results of serum laboratory tests (a white-cell count of less than 4000 per cubic millimeter, a platelet count of less than 100,000 per cubic millimeter, a blood urea nitrogen level of more than 25 mg per deciliter (8.9 mmol per liter), a serum creatinine level of more than 1.5 mg per deciliter (132.6 µmol per liter))
- 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 with hemolytic anemia and glucose -6- phosphate dehydrogenase deficiency
- 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
- Individual who are involved in designing, planning or performing this clinical trial
- Patients with medical conditions who are not appropriate to participate the study
- Patients with any condition that could be worsened by supplemental Berberine hydrochloride
Sites / Locations
- Li
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
100mg Berberine hydrochloride group
300mg Berberine hydrochloride group
Placebo oral tablets
Arm Description
Berberine hydrochloride 100mg tablet by mouth, two times per day for 6 months
Berberine hydrochloride 300mg tablet by mouth, two times per day for 6 months
identical-appearing placebo tablets by mouth, two times per day for 6 months
Outcomes
Primary Outcome Measures
Cumulative the numbers and diameters of those colorectal adenomas during Berberine hydrochloride or placebo treatment in patients with familial adenomatous polyposis
The primary objective of this study is to investigate the number and diameters of colorectal polyps after Berberine hydrochloride or placebo intervention. To ascertain that the same area was scored at base line and at month 6, polyps were counted in pairs of photographs. One investigator, other than the endoscopist, who did not know the treatment, performed the scoring. Videotapes were used to resolve ambiguities and confirm polyp counts. The diameter of those colorectal adenomas was measured in millimeters with a graduated scale passed through the colonoscopy biopsy channel.
Secondary Outcome Measures
Full Information
NCT ID
NCT03333265
First Posted
November 2, 2017
Last Updated
July 24, 2022
Sponsor
Xijing Hospital of Digestive Diseases
1. Study Identification
Unique Protocol Identification Number
NCT03333265
Brief Title
Primary Chemoprevention of Familial Adenomatous Polyposis With Berberine Hydrochloride
Official Title
The Effect of Berberine Hydrochloride in Familial Adenomatous Polyposis:a Prospective, Randomized, Double Blind, Placebo-controlled, Multicenter Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
September 1, 2017 (Actual)
Primary Completion Date
August 31, 2020 (Actual)
Study Completion Date
June 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Xijing Hospital of Digestive Diseases
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
In recent years, Berberine hydrochloride has been reported to inhibit cancer cell proliferation and to be cytotoxic towards cancer cells. Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. The aim of this study is to investigate the chemopreventive effects Berberine hydrochlorid on the regression of colorectal adenomas.
Detailed Description
Familial adenomatous polyposis is an autosomal dominant syndrome caused by a germ-line mutation of the adenomatous polyposis coli (APC) gene located at chromosome 5q21. The disorder is characterized by the development of hundreds of colorectal adenomas during adolescence. Colorectal cancer will develop in nearly all affected persons by the sixth decade of life if prophylactic colectomy is not performed. Because the adenoma-to-carcinoma sequence in familial adenomatous polyposis resembles sporadic colon carcinogenesis, studies of familial adenomatous polyposis may contribute to the prevention of sporadic adenomas and colon cancer.
BBR, an isoquinoline alkaloid, is a natural compound in numerous Chinese herb plants such as Berberisaristata, Coptischinensis, Coptis rhizome, etc. In recent years, Berberine hydrochloride has been reported to inhibit cancer cell proliferation and to be cytotoxic towards cancer cells. The aim of this study is to investigate the regression effect of Berberine hydrochloride on the colorectal adenomas in patients with familial adenomatous polyposis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Adenomas
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
100mg Berberine hydrochloride group
Arm Type
Experimental
Arm Description
Berberine hydrochloride 100mg tablet by mouth, two times per day for 6 months
Arm Title
300mg Berberine hydrochloride group
Arm Type
Experimental
Arm Description
Berberine hydrochloride 300mg tablet by mouth, two times per day for 6 months
Arm Title
Placebo oral tablets
Arm Type
Placebo Comparator
Arm Description
identical-appearing placebo tablets by mouth, two times per day for 6 months
Intervention Type
Drug
Intervention Name(s)
100mg Berberine hydrochloride
Other Intervention Name(s)
100mg Berberine hydrochloride tablet ("Sine Tianping")
Intervention Description
patients take the Berberine hydrochloride 100mg tablet by mouth, 2 times a day with 6 months
Intervention Type
Drug
Intervention Name(s)
300mg Berberine hydrochloride
Other Intervention Name(s)
300mg Berberine hydrochloride tablet ("Sine Tianping")
Intervention Description
patients take the Berberine hydrochloride 300mg tablet by mouth, 2 times a day with 6 months
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Other Intervention Name(s)
Placebo (for Berberine hydrochloride)
Intervention Description
patients take mmic Berberine hydrochloride tablet by mouth, 2 times a day with 6 months
Primary Outcome Measure Information:
Title
Cumulative the numbers and diameters of those colorectal adenomas during Berberine hydrochloride or placebo treatment in patients with familial adenomatous polyposis
Description
The primary objective of this study is to investigate the number and diameters of colorectal polyps after Berberine hydrochloride or placebo intervention. To ascertain that the same area was scored at base line and at month 6, polyps were counted in pairs of photographs. One investigator, other than the endoscopist, who did not know the treatment, performed the scoring. Videotapes were used to resolve ambiguities and confirm polyp counts. The diameter of those colorectal adenomas was measured in millimeters with a graduated scale passed through the colonoscopy biopsy channel.
Time Frame
From baseline to 6 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients aged 18-65 years
Patients with familial adenomatous polyposis, who had not had their entire colorectum removed, and who had five or more polyps 2 mm or more in diameter that could be assessed endoscopically
All potential subjects received genetic counseling before undergoing genetic testing for APC gene mutations.
Eligible subjects had a disease-causing mutation of the APC gene but had no endoscopically detectable colorectal adenomatous polyps and no history of colonic surgery
Exclusion Criteria:
Patients who are hypersensitive or intolerant to the drugs
Patients who had a history of colectomy or colectomy anticipated within 8 months after randomization
Patients with abnormal results of serum laboratory tests (a white-cell count of less than 4000 per cubic millimeter, a platelet count of less than 100,000 per cubic millimeter, a blood urea nitrogen level of more than 25 mg per deciliter (8.9 mmol per liter), a serum creatinine level of more than 1.5 mg per deciliter (132.6 µmol per liter))
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 with hemolytic anemia and glucose -6- phosphate dehydrogenase deficiency
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
Individual who are involved in designing, planning or performing this clinical trial
Patients with medical conditions who are not appropriate to participate the study
Patients with any condition that could be worsened by supplemental Berberine hydrochloride
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weizhong Wang, MD,PH.D
Organizational Affiliation
Xijing digestive surgery center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Li
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710000
Country
China
12. IPD Sharing Statement
Learn more about this trial
Primary Chemoprevention of Familial Adenomatous Polyposis With Berberine Hydrochloride
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