Ulcerative ColitisPhase 1NCT02365480
Berberine Chloride in Preventing Colorectal Cancer in Patients With Ulcerative Colitis in Remission
A Phase 1 study testing Berberine Chloride and Laboratory Biomarker Analysis in people with Ulcerative Colitis, run by National Cancer Institute (NCI) at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Berberine Chloride and Laboratory Biomarker Analysis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 16 Jun 2016to 13 Dec 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Phase I Trial of Berberine in Subjects With Ulcerative Colitis
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Ulcerative Colitis
- Being tested
- Berberine Chloride, Laboratory Biomarker Analysis, Placebo Administration
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Berberine ChlorideDrug
Also called Berberine Chloride Dihydrate, Berberine Hydrochloride, Berberinum Chloride
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Placebo AdministrationOther
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (berberine chloride) | Experimental | Patients receive berberine chloride PO TID for 90 days in the absence of disease progression or unacceptable toxicity. Receives: 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. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline to Day 90 (end of intervention)
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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
- = 1/3 of cells stained
- = 1/2 of cells stained
- = ≥ 2/3 of cells stained
Measured: 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.
Measured: 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.
Measured: Baseline to Day 90 (end of intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2015 (estimated)
- Study start16 Jun 2016
- Primary completion16 Feb 2018
- Study completion13 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kaichun Wu, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02365480
- Sponsor's protocol ID
- NCI-2015-00173
- Other IDs
- NCI-2015-00173, N01-CN-2012-00035, NCI2014-03-01, NWU2014-03-01, N01CN00035, P30CA060553
- Status last verified
- Jul 2021
- First submitted
- 17 Feb 2015
- Last updated
- 3 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Berberine in Subjects With Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT02365480
- Acronym / sponsor ID
- NCI-2015-00173
- Conditions
- Ulcerative Colitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 16 Jun 2016 (actual)
- Primary completion
- 16 Feb 2018 (actual)
- Study completion
- 13 Dec 2019 (actual)
- First posted
- 19 Feb 2015 (estimated)
- Results
- Posted 2 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (berberine chloride) | Experimental | Drug: Berberine Chloride, Other: Laboratory Biomarker AnalysisPatients receive berberine chloride PO TID for 90 days in the absence of disease progression or unacceptable toxicity. |
| Arm II (placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: Placebo AdministrationParticipants receive placebo PO TID for 90 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Berberine ChlorideAlso: Berberine Chloride Dihydrate, Berberine Hydrochloride, Berberinum ChlorideGiven PO | Drug | Arm I (berberine chloride) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (berberine chloride), Arm II (placebo) |
| Placebo AdministrationGiven PO | Other | Arm II (placebo) |
Primary outcome
Number of Participants With Clinical Toxicity Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0
Time frame: Baseline up to 30 days post-treatment (up to 120 days total)
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.
Number of Participants With Organ Toxicity Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0
Time frame: Baseline to Day 90 (end of intervention)
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.
5 secondary outcomes
Clinical Efficacy of Berberine Chloride Measured Using the UCDAI Score
Time frame: Baseline to Day 90 (end of intervention)
Change in Plasma Markers of Inflammation Via ELISA
Time frame: Baseline to Day 90 (end of intervention)
Change in Colorectal Tissue Biomarkers Expression by IHC
Time frame: Baseline to Day 90 (end of intervention)
Change in Blood Berberine Chloride Concentration Measurement Using High-performance Liquid Chromatography/Mass Spectrometry
Time frame: Baseline to Day 90 (end of intervention)
Severity of Histologic Inflammation
Time frame: Baseline to Day 90 (end of intervention)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kaichun Wu principal investigator
Northwestern University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Berberine Chloride and Laboratory Biomarker Analysis in people with Ulcerative Colitis, run by National Cancer Institute (NCI) at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Clinical Toxicity Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0 (time frame: Baseline up to 30 days post-treatment (up to 120 days total)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021.