Trial of Indole-3-Carbinol and Silibinin

Smoking Clinical Trial

Official title:

Trial of Indole-3-Carbinol & Silibinin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03687073
• Other study ID #: 2017LS075
• Status: Completed
• Phase: Phase 1
• Start date: November 29, 2018
• Est. completion date: May 7, 2021

Study information

• Verified date: August 2021
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: May 7, 2021
• Est. primary completion date: May 7, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Smoking

Intervention

Drug:
• Indole-3-Carbinol
Cohorts 2, 3, & 4: 400 mg PO BID
• Silibinin
Cohorts 1 & 4: 720mg
• Silibin
Cohort 3: 360mg

Locations

Country	Name	City	State
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of the combination of I3C + Sil	Incidence of Dose Limiting Toxicities (DLTs)	Week 8
Primary	Pharmacokinetic profile of I3C + Sil	AUC	Week 8
Primary	Pharmacokinetic profile of I3C + Sil	Cmax	Week 8
Primary	Pharmacokinetic profile of I3C + Sil	Half-life	Week 8
Primary	Pharmacokinetic profile of I3C + Sil	Elimination rate	Week 8
Primary	Pharmacokinetic profile of I3C + Sil	Plasma clearance	Week 8
Primary	Pharmacokinetic profile of I3C + Sil	Renal clearance	Week 8
Primary	Pharmacokinetic profile of I3C + Sil	Accumulation	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on circulating inflammatory markers	Change in inflammatory markers IL-1B, TNF-a, IL-6, IL-8, Cox-2, prostaglandin E, and C-reactive protein	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on circulating immunophenotype	Change in circulating immunophenotype	Week 8
Secondary	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)	Change in protein expression of phosphorylated-Akt (pAkt), pERK, pSTAT3 and NF-kB from peripheral blood mononuclear cells (PBMC)	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on RNA sequencing from PBMC	Change in of I3C, Sil, or I3C + Sil on	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in buccal cells	Change in PIK3CA pathway signaling in buccal cells	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in oral cavity cells	Change in PIK3CA pathway signaling in oral cavity cells	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in nasal mucosa	Change in PIK3CA pathway signaling in nasal mucosa	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on fasting glucose	Change in fasting glucose	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on fasting insulin	Change in fasting insulin	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on lipid profile	Change in lipid profile	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on leptin	Change in leptin	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on body weight	Change in body weight	Week 8
Secondary	Effect of I3C, Sil, or I3C + Sil on waist circumference	Change in waist circumference	Week 8