Trial of Indole-3-Carbinol and Silibinin

University of Minnesota (UMN)

Status and phase: Completed; Phase 1

Conditions: Smoking

Treatments: Drug: Silibinin; Drug: Silibin; Drug: Indole-3-Carbinol

Study type: Interventional

Funder types: Other

Identifiers

NCT03687073

2017LS075

Details and patient eligibility

About

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.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 4 patient groups

Single-dose PK study

Experimental group

Description:

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.

Treatment:

Drug: Indole-3-Carbinol

Drug: Silibin

Drug: Silibinin

Multi-dose PK Study

Experimental group

Description:

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.

Treatment:

Drug: Indole-3-Carbinol

Drug: Silibin

Drug: Silibinin

Safety Study

Experimental group

Description:

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.

Treatment:

Drug: Indole-3-Carbinol

Drug: Silibin

Drug: Silibinin

Cohort 4 PD Study

Experimental group

Description:

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.

Treatment:

Drug: Indole-3-Carbinol

Drug: Silibin

Drug: Silibinin