Trial Outcomes & Findings for Berberine Chloride in Preventing Colorectal Cancer in Patients With Ulcerative Colitis in Remission (NCT NCT02365480)

Last Updated: 2021-08-03

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

Baseline up to 30 days post-treatment (up to 120 days total)

Results posted on

2021-08-03

Participant Flow

The trial opened to accrual 06/16/2016 and closed to accrual 10/18/2017. All participants were recruited at Xijing Hospital, Xi'an, China.

Twenty participants were screened and eighteen were randomized and began study intervention.

Participant milestones

Participant milestones
Measure	Arm I (Berberine Chloride) 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 II (Placebo) 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
Overall Study STARTED	14	4
Overall Study COMPLETED	12	4
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Berberine Chloride) 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 II (Placebo) 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
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline up to 30 days post-treatment (up to 120 days total)

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

Outcome measures

Outcome measures
Measure	Arm I (Berberine Chloride) n=14 Participants 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 II (Placebo) n=4 Participants 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
Number of Participants With Clinical Toxicity Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0	2 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline to Day 90 (end of intervention)

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

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.

Outcome measures

Outcome measures
Measure	Arm I (Berberine Chloride) n=14 Participants 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 II (Placebo) n=4 Participants 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
Number of Participants With Organ Toxicity Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Day 90 (end of intervention)

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

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.

Outcome measures

Outcome measures
Measure	Arm I (Berberine Chloride) n=12 Participants 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 II (Placebo) n=4 Participants 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
Clinical Efficacy of Berberine Chloride Measured Using the UCDAI Score Day 90 (end of intervention)	0.5 score on a scale Standard Deviation 0.5	0.5 score on a scale Standard Deviation 0.5
Clinical Efficacy of Berberine Chloride Measured Using the UCDAI Score Baseline	0.83 score on a scale Standard Deviation 0.37	1 score on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline to Day 90 (end of intervention)

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

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

Outcome measures

Outcome measures
Measure	Arm I (Berberine Chloride) n=12 Participants 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 II (Placebo) n=4 Participants 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
Change in Plasma Markers of Inflammation Via ELISA Baseline	61.47 pg/mL Standard Deviation 22.47	58.68 pg/mL Standard Deviation 22.35
Change in Plasma Markers of Inflammation Via ELISA Day 90 (end of intervention)	55.06 pg/mL Standard Deviation 19.20	54.68 pg/mL Standard Deviation 3.21

SECONDARY outcome

Timeframe: Baseline to Day 90 (end of intervention)

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

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

Outcome measures

Outcome measures
Measure	Arm I (Berberine Chloride) n=12 Participants 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 II (Placebo) n=4 Participants 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
Change in Colorectal Tissue Biomarkers Expression by IHC Baseline	1.83 score on a scale Standard Deviation 0.90	2.25 score on a scale Standard Deviation 0.43
Change in Colorectal Tissue Biomarkers Expression by IHC Day 90 (end of intervention)	1.33 score on a scale Standard Deviation 0.47	1.5 score on a scale Standard Deviation 0.87

SECONDARY outcome

Timeframe: Baseline to Day 90 (end of intervention)

Population: Participants with ulcerative colitis in clinical remission and maintained by Mesalamine

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

Outcome measures

Outcome measures
Measure	Arm I (Berberine Chloride) n=12 Participants 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 II (Placebo) n=4 Participants 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
Change in Blood Berberine Chloride Concentration Measurement Using High-performance Liquid Chromatography/Mass Spectrometry Baseline	0.20 ng/ml Standard Deviation 0.21	0.09 ng/ml Standard Deviation 0.04
Change in Blood Berberine Chloride Concentration Measurement Using High-performance Liquid Chromatography/Mass Spectrometry Day 90 (end of intervention)	1.16 ng/ml Standard Deviation 1.28	0.18 ng/ml Standard Deviation 0.19

SECONDARY outcome

Timeframe: Baseline to Day 90 (end of intervention)

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

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.

Outcome measures

Outcome measures
Measure	Arm I (Berberine Chloride) n=12 Participants 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 II (Placebo) n=4 Participants 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
Severity of Histologic Inflammation Day 90 (end of intervention)	2.37 score on a scale Standard Deviation 1.66	4.45 score on a scale Standard Deviation 0.92
Severity of Histologic Inflammation Baseline	2.89 score on a scale Standard Deviation 1.41	4.68 score on a scale Standard Deviation 0.58

Adverse Events

Arm I (Berberine Chloride)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Arm II (Placebo)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Arm I (Berberine Chloride) n=14 participants at risk 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 II (Placebo) n=4 participants at risk 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
Gastrointestinal disorders Nausea	7.1% 1/14 • Number of events 1 • 120 days after randomization Adverse events deemed possibly, probably, or definitely related to the study intervention by study physician are reported.	0.00% 0/4 • 120 days after randomization Adverse events deemed possibly, probably, or definitely related to the study intervention by study physician are reported.
Metabolism and nutrition disorders Alanine aminotransferase increased	7.1% 1/14 • Number of events 1 • 120 days after randomization Adverse events deemed possibly, probably, or definitely related to the study intervention by study physician are reported.	0.00% 0/4 • 120 days after randomization Adverse events deemed possibly, probably, or definitely related to the study intervention by study physician are reported.
Metabolism and nutrition disorders Aspartate aminotransferase increased	7.1% 1/14 • Number of events 1 • 120 days after randomization Adverse events deemed possibly, probably, or definitely related to the study intervention by study physician are reported.	0.00% 0/4 • 120 days after randomization Adverse events deemed possibly, probably, or definitely related to the study intervention by study physician are reported.

Additional Information

Seema A. Khan, MD

Northwestern University

Phone: 312-503-4236

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (Berberine Chloride) n=14 Participants 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 II (Placebo) n=4 Participants 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	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants	4 Participants n=7 Participants	18 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	4 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	14 Participants n=5 Participants	4 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment China	14 participants n=5 Participants	4 participants n=7 Participants	18 participants n=5 Participants
BMI	23.5 kilogram per square meter n=5 Participants	22.8 kilogram per square meter n=7 Participants	23.5 kilogram per square meter n=5 Participants