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

NCT02365480 | Completed Phase 1 Results DMC

• 6 other identifiers: NCI-2015-00173N01-CN-2012-00035NCI2014-03-01NWU2014-03-01N01CN00035P30CA060553
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline to Day 90 (end of intervention)

Secondary Outcomes (5)

• Clinical Efficacy of Berberine Chloride Measured Using the UCDAI Score

  Baseline to Day 90 (end of intervention)

• Change in Plasma Markers of Inflammation Via ELISA

  Baseline to Day 90 (end of intervention)

• Change in Colorectal Tissue Biomarkers Expression by IHC

  Baseline to Day 90 (end of intervention)

• Change in Blood Berberine Chloride Concentration Measurement Using High-performance Liquid Chromatography/Mass Spectrometry

  Baseline to Day 90 (end of intervention)

• Severity of Histologic Inflammation

  Baseline to Day 90 (end of intervention)

Study Arms (2)

Arm I (berberine chloride)

EXPERIMENTAL

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

Arm II (placebo)

PLACEBO COMPARATOR

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

Other: Laboratory Biomarker Analysis; Other: Placebo Administration

Interventions

Berberine Chloride DRUG

Given PO

Also known as: Berberine Chloride Dihydrate, Berberine Hydrochloride, Berberinum Chloride

Arm I (berberine chloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (berberine chloride); Arm II (placebo)

Placebo Administration OTHER

Given PO

Arm II (placebo)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with ulcerative colitis in clinical remission (UCDAI) =\< 1 for at least 3 months, regardless of how long ago they were diagnosed for UC
• Receiving maintenance therapy with mesalamine for at least 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Leukocytes \>= 3,000/microliter
• Absolute neutrophil count \>= 1,500/microliter
• Platelets \>= 100,000/microliter
• Total bilirubin within normal institutional limits; higher values (=\< 3 x institutional upper limit of normal \[ULN\]) are acceptable in participants with: 1. known or suspected cholangitis associated with Crohn's disease, or 2, known or suspected inborn errors of metabolism that lead to increased bilirubin
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOP\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional ULN
• Creatinine within normal institutional limits
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Participants who have had any immunomodulatory treatment in the past 3 months will be excluded
• Participants who have taken any medicines that are inducers, inhibitors or substrates of select cytochrome (CYP) isozymes within the past 3 months will be excluded; participants who have consumed either grapefruit juice or Seville orange juice in the past 7 days will be excluded
• Participants with dysplasia-associated mass or lesion (DALM) due to longstanding idiopathic inflammatory bowel disease will be excluded
• Participants who are currently receiving any other investigational agents or have received investigational agents within the past 3 months will be excluded
• Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to berberine will be excluded
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that in the opinion of investigators would jeopardize patient safety of data integrity are excluded; individuals who are human immunodeficiency virus (HIV) positive will not necessarily be excluded, will be considered on a case-by-case basis, but will be required to meet criteria related to patient safety and data integrity, as assessed by investigators
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with berberine; women are considered to be of child-bearing potential if they are not surgically sterile or under the age 65 and have menstruated within the last two years

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Fourth Military Medical University

Xi'an, Shaanxi, 710032, China

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Seema A. Khan, MD
• Organization: Northwestern University

s-khan2@northwestern.edu

312-503-4236

Study Officials

• Kaichun Wu

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2015
• First Posted: February 19, 2015
• Study Start: June 16, 2016
• Primary Completion: February 16, 2018
• Study Completion: December 13, 2019
• Last Updated: August 3, 2021
• Results First Posted: June 2, 2021

Record last verified: 2021-07

Locations

CN (1); US (1)