Digestive System Diseases

All Conditions

Symptoms and General Pathology

Colitis

Colitis, Ulcerative

Ulcer

Gastroenteritis

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Inflammatory Bowel Diseases

Patients receive berberine chloride PO TID for 90 days in the absence of disease progression or unacceptable toxicity.

Participants receive placebo PO TID for 90 days in the absence of disease progression or unacceptable toxicity.

Berberine Chloride

Laboratory Biomarker Analysis

Placebo Administration

Kaichun Wu

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.

Berberine Chloride in Preventing Colorectal Cancer in Patients With Ulcerative Colitis in Remission

Phase I Trial of Berberine in Subjects With Ulcerative Colitis

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.

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.

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.

TNF-α, a cytokine plasma-based measure of inflammation, measured by enzyme linked immunosorbent assay (ELISA). A numeric value in pg/mL.

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

Change in blood berberine chloride concentration measurement measured using high-performance liquid chromatography/mass spectrometry.

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.

National Cancer Institute (NCI)

Adverse events deemed possibly, probably, or definitely related to the study intervention by study physician are reported.

Patients receive berberine chloride PO TID for 90 days in the absence of disease progression or unacceptable toxicity.

Berberine Chloride: Given PO

Laboratory Biomarker Analysis: Correlative studies

Arm I (Berberine Chloride)

Participants receive placebo PO TID for 90 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Placebo Administration: Given PO

Arm II (Placebo)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

China

Region of Enrollment

Seema A. Khan, MD

Participants with ulcerative colitis in clinical remission and maintained by Mesalamine.

Number of Participants With Clinical Toxicity Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0

Number of Participants With Organ Toxicity Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0

Baseline

Day 90 (end of intervention)

Clinical Efficacy of Berberine Chloride Measured Using the UCDAI Score

Change in Plasma Markers of Inflammation Via ELISA

Change in Colorectal Tissue Biomarkers Expression by IHC

Participants with ulcerative colitis in clinical remission and maintained by Mesalamine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Berberine Chloride in Preventing Colorectal Cancer in Patients With Ulcerative Colitis in Remission	NCT02365480	Ulcerative Coli...	Berberine Chlor... Laboratory Biom... Placebo Adminis...	18 Years - 70 Years	National Cancer Institute (NCI)
Berberine Chloride in Preventing Colorectal Cancer in Patients With Ulcerative Colitis in Remission	NCT02365480	Ulcerative Coli...	Berberine Chlor... Laboratory Biom... Placebo Adminis...	18 Years - 70 Years	National Cancer Institute (NCI)

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