Berberine Chloride in Preventing Colorectal Cancer in Patients With Ulcerative Colitis in Remission
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|ClinicalTrials.gov Identifier: NCT02365480|
Recruitment Status : Active, not recruiting
First Posted : February 19, 2015
Last Update Posted : October 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Ulcerative Colitis||Drug: Berberine Chloride Other: Laboratory Biomarker Analysis Other: Placebo||Phase 1|
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.
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 (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Phase I Trial of Berberine in Subjects With Ulcerative Colitis|
|Actual Study Start Date :||June 16, 2016|
|Actual Primary Completion Date :||February 16, 2018|
Experimental: Arm I (berberine chloride)
Patients receive berberine chloride PO TID for 90 days in the absence of disease progression or unacceptable toxicity.
Drug: Berberine Chloride
Other: Laboratory Biomarker Analysis
Placebo Comparator: Arm II (placebo)
Participants receive placebo PO TID for 90 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of grade 2 systemic toxicity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4 [ Time Frame: Up to 30 days post-treatment ]Relevant counts and rates will be evaluated and reported. 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.
- Incidence of organ toxicity [ Time Frame: Up to 90 days (at the end of treatment) ]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.
- Clinical efficacy of berberine chloride measured using the UCDAI score [ Time Frame: At day 90 ]
- Change in plasma markers of inflammation via ELISA [ Time Frame: Baseline up to 90 days ]Descriptive statistics and graphical methods to present the evidence of possible correlations in outcomes of interest. Box plots and confidence intervals will be used to assign proper mass weight to groups of observations. "Before" and "after" intervention values and their difference will be compared with suitably chosen counterparts.
- Change in colorectal tissue biomarkers expression by IHC [ Time Frame: Baseline up to 90 days ]The Ki-67 and cleaved caspase 3 outcomes will be the number of cells positive over total number. The TNFa, COX-2, and NF-κB immunohistochemistry will be done by quantitation through chromovision and will be expressed as % of control (placebo, pre-treatment). Descriptive statistics and graphical methods will be performed to present the evidence of possible correlations in outcomes of interest.
- Change in gene methylation status using methylation-specific polymerase chain reaction strategy [ Time Frame: Baseline up to 90 days ]The description and comparison of gene methylation status will be performed both with the view of before - after possible change within each treatment group, as well as with the view of treatment - control groups for before and for the after period. Descriptive statistics and graphical methods will be performed to present the evidence of possible correlations in outcomes of interest.
- Change in blood berberine chloride concentration measurement using high-performance liquid chromatography/mass spectrometry [ Time Frame: Baseline up to 90 days ]
- Severity of histologic inflammation [ Time Frame: Up to 90 days ]Histologic sections will be stained with hematoxylin and eosin and the severity of histologic inflammation will be evaluated using the Geboes grading system.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02365480
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Fourth Military Medical University|
|Xi'an, Shaanxi, China, 710032|
|Principal Investigator:||Kaichun Wu||Northwestern University|