Trial of Indole-3-Carbinol and Silibinin

August 10, 2021 updated by: Masonic Cancer Center, University of Minnesota

Trial of Indole-3-Carbinol & Silibinin

This is a non-therapeutic, Phase 1 clinical trial to examine the safety, pharmacokinetic (PK) characteristics, and pharmacodynamics (PD) effect of indole-3-carbinol (I3C) and silibinin (Sil) in healthy subjects.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center at University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult ≥ 18 years old
  • Current smoker of ≥ 8 cigarettes per day for at least the last 6 months by self-report

  • Adequate blood counts, and adequate liver and kidney function defined as follows:

    • Hemoglobin ≥ 9 g/dL for women, ≥ 10 g/dL for men
    • Platelet count ≥ 100 x 10^9/L
    • Total bilirubin ≤ Institutional upper limit of normal (≤ 1.3 mg/dL for UMMC)
    • ALT ≤ 1.5 times institutional upper limit of normal
    • Creatinine ≤ 1.4 g/dL and estimated GFR ≥ 80 mL/min/1.7m2
  • Able to understand the experimental nature of the study and provide informed written consent

Exclusion Criteria:

  • Chronic proton pump inhibitor, H2-blocker (i.e., ranitidine, famotidine), and/or calcium carbonate use
  • History of gastric bypass surgery, gastric banding, bowel resection, malabsorption syndromes such as celiac sprue or pancreatic insufficiency, or other conditions that may affect gastric or intestinal absorption of nutrients
  • Current use of tobacco products other than cigarettes (i.e. snuff, snuz, smokeless tobacco, cigars, pipes), or use of these products within 3 months of study registration
  • Major or chronic medical disease, including heart disease, poorly controlled diabetes, etc., to be adjudicated by the principal investigator
  • Known active malignancy
  • History of aerodigestive malignancies
  • Women who are pregnant, intend to become pregnant within 3 months of study registration, or who are lactating. Women of childbearing potential must have a negative urine pregnancy test within 14 days of starting the assigned intervention
  • Antibiotic use within 2 months of study registration by self-report
  • History of respiratory tract cancer
  • Known allergy to I3C, Sil, or its components
  • Psychiatric and/or social situations that would potentially limit compliance with study requirements

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Single-dose PK study
Subjects will take the assigned dose of I3C, Sil, or I3C + Sil once at the study center. Ten mL of blood will be collected at the time points described in Section 9.14. Concurrently, urine will also be collected for 24 hours after the first dose of I3C, Sil or I3C + Sil, divided into the time intervals.
Drug: Indole-3-Carbinol
Cohorts 2, 3, & 4: 400 mg PO BID
Other Names:
  • 13C
Drug: Silibinin
Cohorts 1 & 4: 720mg
Other Names:
  • Sil
Drug: Silibin
Cohort 3: 360mg
Other Names:
  • Sil
Experimental: Multi-dose PK Study
Subjects will take the assigned dose of I3C, Sil, or I3C + Sil for 8 weeks. Ten mL of blood will be collected at the time points described in Section 9.14. Concurrently, urine will be collected for 24 hours after the first dose of I3C, Sil or I3C + Sil, divided into the time intervals.
Drug: Indole-3-Carbinol
Cohorts 2, 3, & 4: 400 mg PO BID
Other Names:
  • 13C
Drug: Silibinin
Cohorts 1 & 4: 720mg
Other Names:
  • Sil
Drug: Silibin
Cohort 3: 360mg
Other Names:
  • Sil
Experimental: Safety Study
Safety data will be generated during the multi-dose PK and PD study, as DLT is not anticipated in the single-dose PK study. Enrollment into dose cohorts 1 and 2 can occur on a continuous basis. Enrollment for dose cohorts 3 and 4 will be done sequentially using a modified 3+3 design (see Section 8.2). The first three subjects enrolled into a dose cohort must complete at least 21 days of the multi-dose PK/PD study without a DLT before the remaining 4 subjects in the cohort can be enrolled.
Drug: Indole-3-Carbinol
Cohorts 2, 3, & 4: 400 mg PO BID
Other Names:
  • 13C
Drug: Silibinin
Cohorts 1 & 4: 720mg
Other Names:
  • Sil
Drug: Silibin
Cohort 3: 360mg
Other Names:
  • Sil
Experimental: Cohort 4 PD Study
The effect of I3C, Sil, or I3C + Sil on the pharmacodynamic endpoints listed under the Secondary Objectives in Section 1.2 will be characterized. This PD study will be done concurrently with the multi-dose PK study. Subjects will take the assigned dose of I3C, Sil, or I3C + Sil for 8 weeks. Nasal epithelium, oral cavity cells, buccal cells, blood, and urine will be collected at the time points described in the study calendar in Section 4.0.
Drug: Indole-3-Carbinol
Cohorts 2, 3, & 4: 400 mg PO BID
Other Names:
  • 13C
Drug: Silibinin
Cohorts 1 & 4: 720mg
Other Names:
  • Sil
Drug: Silibin
Cohort 3: 360mg
Other Names:
  • Sil

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety of the combination of I3C + Sil
Time Frame: Week 8
Incidence of Dose Limiting Toxicities (DLTs)
Week 8
Pharmacokinetic profile of I3C + Sil
Time Frame: Week 8
AUC
Week 8
Pharmacokinetic profile of I3C + Sil
Time Frame: Week 8
Cmax
Week 8
Pharmacokinetic profile of I3C + Sil
Time Frame: Week 8
Half-life
Week 8
Pharmacokinetic profile of I3C + Sil
Time Frame: Week 8
Elimination rate
Week 8
Pharmacokinetic profile of I3C + Sil
Time Frame: Week 8
Plasma clearance
Week 8
Pharmacokinetic profile of I3C + Sil
Time Frame: Week 8
Renal clearance
Week 8
Pharmacokinetic profile of I3C + Sil
Time Frame: Week 8
Accumulation
Week 8

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Effect of I3C, Sil, or I3C + Sil on circulating inflammatory markers
Time Frame: Week 8
Change in inflammatory markers IL-1B, TNF-a, IL-6, IL-8, Cox-2, prostaglandin E, and C-reactive protein
Week 8
Effect of I3C, Sil, or I3C + Sil on circulating immunophenotype
Time Frame: Week 8
Change in circulating immunophenotype
Week 8
Effect of I3C, Sil, or I3C + Sil on protein expression of phosphorylated-Akt (pAkt), pERK, pSTAT3 and NF-kB from peripheral blood mononuclear cells (PBMC)
Time Frame: Week 8
Change in protein expression of phosphorylated-Akt (pAkt), pERK, pSTAT3 and NF-kB from peripheral blood mononuclear cells (PBMC)
Week 8
Effect of I3C, Sil, or I3C + Sil on RNA sequencing from PBMC
Time Frame: Week 8
Change in of I3C, Sil, or I3C + Sil on
Week 8
Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in buccal cells
Time Frame: Week 8
Change in PIK3CA pathway signaling in buccal cells
Week 8
Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in oral cavity cells
Time Frame: Week 8
Change in PIK3CA pathway signaling in oral cavity cells
Week 8
Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in nasal mucosa
Time Frame: Week 8
Change in PIK3CA pathway signaling in nasal mucosa
Week 8
Effect of I3C, Sil, or I3C + Sil on fasting glucose
Time Frame: Week 8
Change in fasting glucose
Week 8
Effect of I3C, Sil, or I3C + Sil on fasting insulin
Time Frame: Week 8
Change in fasting insulin
Week 8
Effect of I3C, Sil, or I3C + Sil on lipid profile
Time Frame: Week 8
Change in lipid profile
Week 8
Effect of I3C, Sil, or I3C + Sil on leptin
Time Frame: Week 8
Change in leptin
Week 8
Effect of I3C, Sil, or I3C + Sil on body weight
Time Frame: Week 8
Change in body weight
Week 8
Effect of I3C, Sil, or I3C + Sil on waist circumference
Time Frame: Week 8
Change in waist circumference
Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Masonic Cancer Center, University of Minnesota

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Naomi Fujioka, MD, Division of Hematology, Oncology and Transplantation, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 29, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 7, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 7, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 14, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 27, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 11, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 10, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2017LS075

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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