This randomized, pilot phase I trial studies the side effects of berberine chloride in treating patients with ulcerative colitis and who are in remission (a decrease in or disappearance of signs and symptoms of cancer) to reduce the risk of colorectal cancer. Patients with ulcerative colitis are at increased risk for colorectal cancer. Chemoprevention is the use of drugs, such as berberine chloride, to keep a disease/condition from forming or coming back. The use of berberine chloride may keep colorectal cancer from forming in patients with ulcerative colitis.
PRIMARY OBJECTIVES: I. To determine the safety of berberine (berberine chloride) administered to participants with ulcerative colitis (UC) in clinical remission while receiving maintenance therapy with mesalamine. SECONDARY OBJECTIVES: I. Determine the molecular efficacy of berberine by examining the following biomarkers: * Plasma-based measures of inflammation, including the blood C-reaction protein (CRP) level, erythrocyte sedimentation rate (ESR), and cytokines such as TNFa, IL-4, IL-6, IL-8 and IL-10 measured by enzyme-linked immunosorbent assay (ELISA). * Tissue-based measures of inflammation, including TNFα, COX-2, and NF-kappa (κ)B by immunohistochemistry (IHC), and anti-cancer action, including antigen Ki-67 (Ki67) and activated caspase-3 by IHC, and deoxyribonucleic acid (DNA) methylation on SFRP1, TCERG1L FBN2, TFPI2 using the methylation-specific polymerase chain reaction (qMSP) strategy. II. Clinical efficacy: UC related symptoms will be measured using the Ulcerative Colitis Disease Activity Index (i.e. the Mayo score) (UCDAI). III. Histological analysis for inflammation: severity of histologic inflammation will be evaluated using the Geboes grading system. IV. Determine plasma concentration of berberine. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive berberine chloride orally (PO) thrice daily (TID) for 90 days in the absence of disease progression or unacceptable toxicity. ARM II: Participants receive placebo PO TID for 90 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are follow-up for 30 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
18
Given PO
Correlative studies
Given PO
Northwestern University
Chicago, Illinois, United States
Fourth Military Medical University
Xi'an, Shaanxi, China
Number of Participants With Clinical Toxicity Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0
Relevant counts and rates will be evaluated and reported by standard clinical tests. Symptoms such as fever, fatigue, weight loss, appetite, stool frequency, bloody stool and other upper and lower gastrointestinal tract symptoms in participants will be observed and recorded.
Time frame: Baseline up to 30 days post-treatment (up to 120 days total)
Number of Participants With Organ Toxicity Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0
Evaluated by standard clinical tests. Symptoms such as fever, fatigue, weight loss, appetite, stool frequency, bloody stool and other upper and lower gastrointestinal tract symptoms in participants will be observed and recorded.
Time frame: Baseline to Day 90 (end of intervention)
Clinical Efficacy of Berberine Chloride Measured Using the UCDAI Score
UC related symptoms measured using the Ulcerative Colitis Disease Activity Index \[UCDAI\]. Score results may range from 0 to 12. 0 indicates normal disease and a higher score up to 12 indicates severe disease.
Time frame: Baseline to Day 90 (end of intervention)
Change in Plasma Markers of Inflammation Via ELISA
TNF-α, a cytokine plasma-based measure of inflammation, measured by enzyme linked immunosorbent assay (ELISA). A numeric value in pg/mL.
Time frame: Baseline to Day 90 (end of intervention)
Change in Colorectal Tissue Biomarkers Expression by IHC
Ki-67, a tissue based measure of inflammation, staining was graded and scored on a scale. The higher the score, the greater the expression of Ki-67: 0 = no cells stained 1. = 1/3 of cells stained 2. = 1/2 of cells stained 3. = ≥ 2/3 of cells stained
Time frame: Baseline to Day 90 (end of intervention)
Change in Blood Berberine Chloride Concentration Measurement Using High-performance Liquid Chromatography/Mass Spectrometry
Change in blood berberine chloride concentration measurement measured using high-performance liquid chromatography/mass spectrometry.
Time frame: Baseline to Day 90 (end of intervention)
Severity of Histologic Inflammation
Histologic sections will be stained with hematoxylin and eosin and the severity of histologic inflammation will be evaluated using the Geboes scoring system. The Geboes score is taken as the highest category of change among the following: 0.0-0.3, structural change only; 1.0-1.3, chronic inflammation; 2.0-2.3, lamina propria neutrophils; 3.0-3.3, neutrophils in epithelium; 4.0-4.3, crypt destruction; and 5.0-5.4, erosions or ulcers.
Time frame: Baseline to Day 90 (end of intervention)
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